PHOTO

Kuniyasu Niizuma
Section
Graduate School of Biomedical Engineering
Job title
Professor
Degree
  • 博士(医学)(東北大学)

Professional Memberships 12

  • 日本神経内視鏡学会

  • 日本脳神経CI学会

  • Japanese Society of Spinal Surgery

  • Japanese Society for Magnetic Resonance in Medicine

  • The Japanese Congress of Neurological Surgeons

  • The Japan Society of Molecular Neurosurgery

  • The Japanese Society of Cerebral Blood Flow and Metabolism

  • The Japan Stroke Society

  • Japanse Society on Surgery for Cerebral Stroke

  • The Japanese Society for Regenerative Medicine

  • The Japanese Society for Neuroendovascular Therapy

  • The Japan Neurosurgical Society

︎Show all ︎Show first 5

Research Interests 5

  • 脳梗塞

  • 再生医療

  • 脳神経外科

  • 脳卒中

  • 脳血管内治療

Research Areas 1

  • Life sciences / Neurosurgery /

Awards 1

  1. 第15回日本脳神経外科学会奨励賞

    2009/10/15 日本脳神経外科学会

Papers 234

  1. Cerebral venous sinus thrombosis detected using diffusion-weighted magnetic resonance imaging during maintenance temozolomide chemotherapy in a patient with glioblastoma: illustrative case. International-journal

    Youhei Takeuchi, Ryuta Saito, Masayuki Kanamori, Kuniyasu Niizuma, Shunji Mugikura, Hidenori Endo

    Journal of neurosurgery. Case lessons 7 (9) 2024/02/26

    DOI: 10.3171/CASE23762  

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    BACKGROUND: Cerebral venous sinus thrombosis (CVST) sometimes occurs in the background of hypercoagulopathic disorders, including malignancy, chemotherapy, etc. Glioblastoma (GBM) is a malignancy found in the central nervous system, and reports on cases of GBM complicated by CVST are sparse. The authors herein report a case of GBM complicated by CVST during maintenance temozolomide (TMZ) chemotherapy and describe the utility of diffusion-weighted magnetic resonance imaging (MRI) for the detection of CVST. OBSERVATIONS: A 65-year-old male was treated for left temporal GBM. After surgical removal of the lesion, the patient was treated with chemoradiation therapy, which included 60 Gy local radiation with concomitant TMZ chemotherapy. He was subsequently received TMZ maintenance therapy. Routine MRI performed 7 months after surgery revealed no evidence of tumor recurrence. However, diffusion-weighted imaging (DWI) revealed a high-intensity signal at the posterior portion of the superior sagittal sinus, indicating the presence of a thrombus. In addition to the preexisting symptoms, the patient experienced some disorientation. Angiography revealed an obstruction in the superior sagittal sinus, right transverse sinus, right sigmoid sinus, and straight sinus. His symptoms improved with endovascular and anticoagulant therapy. LESSONS: Performing DWI during routine follow-up can help in the early diagnosis of CVST in patients with malignant gliomas.

  2. Distinguishing IDH mutation status in gliomas using FTIR-ATR spectra of peripheral blood plasma indicating clear traces of protein amyloid aggregation. International-journal

    Saiko Kino, Masayuki Kanamori, Yoshiteru Shimoda, Kuniyasu Niizuma, Hidenori Endo, Yuji Matsuura

    BMC cancer 24 (1) 222-222 2024/02/16

    DOI: 10.1186/s12885-024-11970-y  

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    BACKGROUND: Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate dehydrogenase (IDH) gene are strong predictors of treatment sensitivity and prognosis. In this study, we attempted to non-invasively diagnose glioma development and the presence of IDH mutations using multivariate analysis of the plasma mid-infrared absorption spectra for a comprehensive and sensitive view of changes in blood components associated with the disease and genetic mutations. These component changes are discussed in terms of absorption wavenumbers that contribute to differentiation. METHODS: Plasma samples were collected at our institutes from 84 patients with glioma (13 oligodendrogliomas, 17 IDH-mutant astrocytoma, 7 IDH wild-type diffuse glioma, and 47 glioblastomas) before treatment initiation and 72 healthy participants. FTIR-ATR spectra were obtained for each plasma sample, and PLS discriminant analysis was performed using the absorbance of each wavenumber in the fingerprint region of biomolecules as the explanatory variable. This data was used to distinguish patients with glioma from healthy participants and diagnose the presence of IDH mutations. RESULTS: The derived classification algorithm distinguished the patients with glioma from healthy participants with 83% accuracy (area under the curve (AUC) in receiver operating characteristic (ROC) = 0.908) and diagnosed the presence of IDH mutation with 75% accuracy (AUC = 0.752 in ROC) in cross-validation using 30% of the total test data. The characteristic changes in the absorption spectra suggest an increase in the ratio of β-sheet structures in the conformational composition of blood proteins of patients with glioma. Furthermore, these changes were more pronounced in patients with IDH-mutant gliomas. CONCLUSIONS: The plasma infrared absorption spectra could be used to diagnose gliomas and the presence of IDH mutations in gliomas with a high degree of accuracy. The spectral shape of the protein absorption band showed that the ratio of β-sheet structures in blood proteins was significantly higher in patients with glioma than in healthy participants, and protein aggregation was a distinct feature in patients with glioma with IDH mutations.

  3. Translational response to mitochondrial stresses is orchestrated by tRNA modifications. International-journal

    Sherif Rashad, Shadi Al-Mesitef, Abdulrahman Mousa, Yuan Zhou, Daisuke Ando, Guangxin Sun, Tomoko Fukuuchi, Yuko Iwasaki, Jingdong Xiang, Shane R Byrne, Jingjing Sun, Masamitsu Maekawa, Daisuke Saigusa, Thomas J Begley, Peter C Dedon, Kuniyasu Niizuma

    bioRxiv : the preprint server for biology 2024/02/14

    DOI: 10.1101/2024.02.14.580389  

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    Mitochondrial stress and dysfunction play important roles in many pathologies. However, how cells respond to mitochondrial stress is not fully understood. Here, we examined the translational response to electron transport chain (ETC) inhibition and arsenite induced mitochondrial stresses. Our analysis revealed that during mitochondrial stress, tRNA modifications (namely f5C, hm5C, queuosine and its derivatives, and mcm5U) dynamically change to fine tune codon decoding, usage, and optimality. These changes in codon optimality drive the translation of many pathways and gene sets, such as the ATF4 pathway and selenoproteins, involved in the cellular response to mitochondrial stress. We further examined several of these modifications using targeted approaches. ALKBH1 knockout (KO) abrogated f5C and hm5C levels and led to mitochondrial dysfunction, reduced proliferation, and impacted mRNA translation rates. Our analysis revealed that tRNA queuosine (tRNA-Q) is a master regulator of the mitochondrial stress response. KO of QTRT1 or QTRT2, the enzymes responsible for tRNA-Q synthesis, led to mitochondrial dysfunction, translational dysregulation, and metabolic alterations in mitochondria-related pathways, without altering cellular proliferation. In addition, our analysis revealed that tRNA-Q loss led to a domino effect on various tRNA modifications. Some of these changes could be explained by metabolic profiling. Our analysis also revealed that utilizing serum deprivation or alteration with Queuine supplementation to study tRNA-Q or stress response can introduce various confounding factors by altering many other tRNA modifications. In summary, our data show that tRNA modifications are master regulators of the mitochondrial stress response by driving changes in codon decoding.

  4. Assessment of language lateralization in epilepsy patients using the super-selective Wada test. International-journal

    Kazuo Kakinuma, Shin-Ichiro Osawa, Kazuto Katsuse, Hiroaki Hosokawa, Kazushi Ukishiro, Kazutaka Jin, Kuniyasu Niizuma, Teiji Tominaga, Hidenori Endo, Nobukazu Nakasato, Kyoko Suzuki

    Acta neurochirurgica 166 (1) 77-77 2024/02/10

    DOI: 10.1007/s00701-024-05957-8  

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    BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.

  5. The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease. International-journal

    Ryosuke Tashiro, Riki Anzawa, Tomoo Inoue, Ayame Mikagi, Dan Ozaki, Keita Tominaga, Takashi Inoue, Tomohisa Ishida, Miki Fujimura, Toyonobu Usuki, Hidenori Endo, Kuniyasu Niizuma, Teiji Tominaga

    Bioorganic & medicinal chemistry 100 117602-117602 2024/02/01

    DOI: 10.1016/j.bmc.2024.117602  

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    Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

  6. [Academia-Industry Alliance: Recent Trend].

    Atsuhiro Nakagawa, Leor Perl, John Lee, Narumi Harada-Shoji, Chiharu Ota, Takuya Shiga, Sako Sunami, Kuniyasu Niizuma, Hidenori Endo, Hideo Harigae, Teiji Tominaga

    No shinkei geka. Neurological surgery 52 (1) 213-225 2024/01

    DOI: 10.11477/mf.1436204899  

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    Industry-academia Collaboration is an academic activity within academia(educational institutions such as universities, research institutes, etc.)formed to research and develop new technologies, create new businesses and knowledge, and recruit outsourcing human resources. There is a collaboration between an industry(a private company, a group that engages in broad commercial activities and links research and development directly to economic activity)and academia. Amidst the dramatic changes in the environment surrounding the goals of research and development of new technologies and the creation of new businesses, there are changes in what academia can do complementarily. We will outline the changes and current situation, including the efforts of the Tohoku University Hospital.

  7. Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case. International-journal

    Mayuko Otomo, Shin-Ichiro Osawa, Kyoko Suzuki, Kazuo Kakinuma, Kazushi Ukishiro, Hiroyoshi Suzuki, Kuniyasu Niizuma, Norio Narita, Nobukazu Nakasato, Teiji Tominaga

    Journal of neurosurgery. Case lessons 6 (26) 2023/12/25

    DOI: 10.3171/CASE23451  

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    BACKGROUND: Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol. OBSERVATIONS: A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors' assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range. LESSONS: An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

  8. Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury. International-journal

    Juntaro Koyama, Shinichi Yamashita, Yuya Kato, Kunihisa Nezu, Takuro Goto, Shinji Fujii, Yu Suzuki, Atsushi Nakayashiki, Yoshihide Kawasaki, Naoki Kawamorita, Hitomi Okita, Takako Ito, Yoshihiro Kushida, Masafumi Goto, Mari Dezawa, Teiji Tominaga, Kuniyasu Niizuma, Akihiro Ito

    BJU international 2023/11/20

    DOI: 10.1111/bju.16232  

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    OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

  9. Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation. International-journal

    Yohei Kawana, Junta Imai, Yosuke M Morizawa, Yoko Ikoma, Masato Kohata, Hiroshi Komamura, Toshihiro Sato, Tomohito Izumi, Junpei Yamamoto, Akira Endo, Hiroto Sugawara, Haremaru Kubo, Shinichiro Hosaka, Yuichiro Munakata, Yoichiro Asai, Shinjiro Kodama, Kei Takahashi, Keizo Kaneko, Shojiro Sawada, Tetsuya Yamada, Akira Ito, Kuniyasu Niizuma, Teiji Tominaga, Akihiro Yamanaka, Ko Matsui, Hideki Katagiri

    Nature biomedical engineering 2023/11/09

    DOI: 10.1038/s41551-023-01113-2  

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    The enhancement of insulin secretion and of the proliferation of pancreatic β cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to β cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2. One method involves subdiaphragmatic implantation of an optical fibre for the photostimulation of cholinergic neurons expressing a blue-light-sensitive opsin. The other method, which suppressed streptozotocin-induced hyperglycaemia in the mice, involves the selective activation of vagal fibres by placing blue-light-emitting lanthanide microparticles in the pancreatic ducts of opsin-expressing mice, followed by near-infrared illumination. The two methods show that signals from the vagal nerve, especially from nerve fibres innervating the pancreas, are sufficient to regulate insulin secretion and β cell proliferation.

  10. Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury. International-journal

    Yoshiharu Takahashi, Takumi Kajitani, Toshiki Endo, Atsushi Nakayashiki, Tomoo Inoue, Kuniyasu Niizuma, Teiji Tominaga

    International journal of molecular sciences 24 (19) 2023/09/27

    DOI: 10.3390/ijms241914603  

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    Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

  11. Randomized placebo-controlled trial of CL2020, an allogenic muse cell-based product, in subacute ischemic stroke. International-journal

    Kuniyasu Niizuma, Shin-Ichiro Osawa, Hidenori Endo, Shin-Ichi Izumi, Kota Ataka, Akihiro Hirakawa, Masao Iwano, Teiji Tominaga

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 43 (12) 271678X231202594-2039 2023/09/27

    DOI: 10.1177/0271678X231202594  

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    Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).

  12. Six-month Outcomes after PulseRider- and Conventional Single Stent-assisted Embolization for Bifurcation Aneurysms: A Propensity-adjusted Comparison.

    Shunsuke Omodaka, Yasushi Matsumoto, Takeshi Fujimori, Hiroyuki Sakata, Kenichi Sato, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

    Neurologia medico-chirurgica 63 (11) 512-518 2023/09/23

    DOI: 10.2176/jns-nmc.2023-0082  

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    Endovascular treatment of wide-necked bifurcation aneurysms (WNBAs) remains challenging despite using a stent. PulseRider is a novel device specifically designed to treat WNBAs, protecting both daughter branches, but the outcomes have not been compared with conventional single stent-assisted embolization. This study aimed to compare the six-month outcomes of PulseRider and single stent-assisted embolization for intracranial unruptured WNBAs using propensity score adjustment. Between February 2012 and October 2021, 46 unruptured WNBAs (34 basilar and 12 middle cerebral arteries) smaller than 10 mm in diameter were treated with PulseRider-assisted embolization (n = 17) or single stent-assisted embolization (n = 29). The immediate and six-month outcomes were compared using inverse probability of treatment weighting analysis. The immediate adequate occlusion rates for the PulseRider- and single stent-assisted embolization were similar (47.1% vs. 62.1%). At six months, adequate occlusion rates for the two groups were also similar (94.1% vs. 86.2%). However, the complete obliteration rate was significantly high after PulseRider-assisted embolization (88.2% vs. 41.4%, adjusted OR 10.54, 95% CI 1.93-57.63). The angiographical improvement rate was also significantly high after PulseRider-assisted embolization (70.6% vs. 37.9%, adjusted OR 6.06, 95% CI 1.54-23.76). The neurologic thromboembolic complication rate was 0% after PulseRider-assisted embolization and 3.4% after single stent-assisted embolization. PulseRider-assisted embolization of WNBAs smaller than 10 mm in diameter was associated with complete obliteration and angiographical improvement at six months. The unique shape of the PulseRider might contribute to the improved midterm aneurysm occlusion.

  13. 超選択的頭蓋内麻酔薬注入により、患者は焦点切除後の神経症状を主観的に評価できる

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 石田 誠, 新妻 邦泰, 神 一敬, 植松 貢, 中里 信和, 遠藤 英徳

    てんかん研究 41 (2) 358-358 2023/09

    Publisher: (一社)日本てんかん学会

    ISSN:0912-0890

    eISSN:1347-5509

  14. Erratum to "Carotid computed tomography angiography after cobalt-based alloy carotid artery stenting using ultra-high-resolution computed tomography with model-based iterative reconstruction" [Radiol Case Rep 2021;16:3721-8]. International-journal

    Shingo Kayano, Hideki Ota, Yoshimichi Sato, Toshiki Endo, Kuniyasu Niizuma, Ichiro Suzuki, Tsuyoshi Kawamura, Kei Takase

    Radiology case reports 18 (6) 2324-2324 2023/06

    DOI: 10.1016/j.radcr.2023.03.021  

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    [This corrects the article DOI: 10.1016/j.radcr.2021.09.003.].

  15. 【脳動脈瘤の温故知新 現在までの治療を紡ぐ永久保存版】脳血管攣縮の最新治療

    遠藤 英徳, 新妻 邦泰, 冨永 悌二

    脳神経外科速報 33 (2) 208-210 2023/03

    Publisher: (株)メディカ出版

    ISSN:0917-1495

  16. Olfactory Dysfunction, an Often Neglected Symptom of Hydrocephalus: Experience from a Case of Late-Onset Idiopathic Aqueductal Stenosis International-journal

    Naoya Yamazaki, Takafumi Hasegawa, Kensuke Ikeda, Ako Miyata, Shin-ichiro Osawa, Kuniyasu Niizuma, Shigenori Kanno, Teiji Tominaga, Masashi Aoki

    Case Reports in Neurology 15 (1) 41-47 2023/03/01

    Publisher: S. Karger AG

    DOI: 10.1159/000529532  

    eISSN:1662-680X

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    Disturbance of smell is often accompanied with common neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. In addition, patients with head trauma, intracranial tumors, and hydrocephalus can also develop olfactory dysfunction, and some of which can improve with treatment of the underlying disease. In clinical practice, few patients complain of smell disturbances, thus olfactory dysfunction is often overshadowed by visible motor symptoms. Herein, we report a case of late-onset idiopathic aqueductal stenosis, a rare form of adult-onset hydrocephalus in which olfactory dysfunction and gait disturbance was markedly improved after endoscopic ventriculostomy. This case report is expected to make more physicians aware that hydrocephalus can cause olfactory dysfunction and that it can be corrected postoperatively. Furthermore, in addition to motor and neuropsychological function, olfactory function test might be useful for functional assessment before and after surgical treatment of hydrocephalus.

  17. A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol. International-journal

    Takashi Moritoyo, Naoko Nishimura, Keiko Hasegawa, Shinya Ishii, Kenji Kirihara, Munenori Takata, Akiko Kishi Svensson, Yumi Umeda-Kameyama, Shuichi Kawarasaki, Ryoko Ihara, Chie Sakanaka, Yurie Wakabayashi, Kuniyasu Niizuma, Teiji Tominaga, Tsutomu Yamazaki, Keiji Hasumi

    British journal of clinical pharmacology 89 (6) 1809-1819 2022/12/23

    DOI: 10.1111/bcp.15651  

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    AIMS: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation. We aim to evaluate the safety, pharmacokinetics and pharmacodynamics of TMS-007 in healthy volunteers. METHODS: This was a randomized, placebo-controlled, double blind, dose-escalation study, administered as a single intravenous infusion of TMS-007 in cohorts of healthy male Japanese subjects. Six cohorts were planned, but only five were completed. In each cohort (n = 8), individuals were randomized to receive one of five doses of TMS-007 (3, 15, 60, 180 or 360 mg; n = 6) or placebo (n = 2). RESULTS: TMS-007 was generally well tolerated, and no serious adverse events were attributed to the drug. A linear dose-dependency was observed for plasma TMS-007 levels. No symptoms of bleeding were observed on brain MRI analysis, and no bleeding-related responses were found on laboratory testing. The plasma levels of the coagulation factor fibrinogen and the anti-fibrinolysis factor α2 -antiplasmin levels were unchanged after TMS-007 dosing. A slight increase in the plasma level of plasmin-α2 -antiplasmin complex, an index of plasmin formation, was observed in the TMS-007 group in cohort 2. CONCLUSIONS: TMS-007 is generally well tolerated and exhibits favourable pharmacokinetic profiles that warrant further clinical development.

  18. Retiform endothelial hyperplasia mimicking cavernous malformation as a late complication of Gamma Knife radiosurgery. International-journal

    Jun Kawagishi, Hidefumi Jokura, Mika Watanabe, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Hiroyoshi Suzuki, Teiji Tominaga

    Journal of neurosurgery 139 (1) 1-11 2022/12/23

    DOI: 10.3171/2022.11.JNS221535  

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    OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a powerful tool for the management of arteriovenous malformations; however, newly formed mass lesions resembling cavernous malformations are a rare late complication of GKRS. In this retrospective study, the authors tried to clarify the unique histological features of these mass lesions. METHODS: The authors retrospectively reviewed the clinical course of 889 patients who had undergone GKRS for arteriovenous malformations at their institute from 1991 to 2021. Among the 848 patients who had been followed up periodically with neuroradiological imaging, 37 developed a mass lesion mimicking a cavernous malformation and underwent surgical removal of the lesion. The median volume of the original nidus was 3.7 cm3 (range 0.07-30.5 cm3), and the median prescription dose was 21 Gy (range 12-25 Gy). The histological characteristics and radiological and clinical features of the 37 patients were investigated. RESULTS: Histological examination showed an organized hematoma and a structure termed "retiform endothelial hyperplasia" (RFEH) consisting of endothelium forming multiple lumen-like vascular channels mimicking cavernous malformations but lacking the subendothelial connective tissue that forms the typical vascular wall structure found in cavernous angioma and capillary telangiectasia. RFEH was detected a median of 10.8 years (range 3.2-27.4 years) after GKRS. Neuroimaging showed hematoma surrounded by massive brain edema in all 37 patients. Symptoms caused by mass effect of the lesion and perifocal edema worsened relatively rapidly but completely disappeared after surgery. No recurrence or morbidity occurred after the surgery. CONCLUSIONS: The delayed formation of RFEH that is mimicking a cavernous malformation neuroradiologically but is histologically distinct from a vascular malformation is a potential complication of GKRS. Its progressive clinical course suggests that surgical removal should be considered for symptomatic patients and/or patients with an apparent radiological mass sign.

  19. Determination of language areas in patients with epilepsy using the super-selective Wada test. International-journal

    Kazuo Kakinuma, Shin-Ichiro Osawa, Hiroaki Hosokawa, Marie Oyafuso, Shoko Ota, Erena Kobayashi, Nobuko Kawakami, Kazushi Ukishiro, Kazutaka Jin, Makoto Ishida, Takafumi Sato, Mika Sakamoto, Kuniyasu Niizuma, Teiji Tominaga, Nobukazu Nakasato, Kyoko Suzuki

    IBRO neuroscience reports 13 156-163 2022/12

    DOI: 10.1016/j.ibneur.2022.08.002  

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    The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

  20. Isotope-dilution LC-MS/MS analysis of the elastin crosslinkers desmosine and isodesmosine in acute cerebral stroke patients. International-journal

    Ayame Mikagi, Ryosuke Tashiro, Tomoo Inoue, Riki Anzawa, Akiho Imura, Takahiro Tanigawa, Tomohisa Ishida, Takashi Inoue, Kuniyasu Niizuma, Teiji Tominaga, Toyonobu Usuki

    RSC advances 12 (49) 31769-31777 2022/11/03

    DOI: 10.1039/d2ra06009d  

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    Utilizing chemically synthesized an isotopically labeled internal standard, isodesmosine-13C3,15N1, an isotope-dilution LC-MS/MS method was established. Concentrations of desmosine and isodesmosine in plasma of acute cerebral stroke patients and healthy controls were determined. The concentration of desmosines was markedly higher in plasma from acute stroke patients compared with healthy controls. Desmosines are thus novel biomarkers for evaluating the extent of vascular injury after acute cerebral stroke.

  21. Piezo Actuator-Driven Pulsed Water Jet for Neurosurgery: Laboratory Evaluation with the Swine Model and Implications of Mechanical Properties. International-journal

    Atsuhiro Nakagawa, Toshiki Endo, Tomohiro Kawaguchi, Masato Yamada, Chiaki Sato, Toshihiro Kumabe, Masaki Iwasaki, Kuniyasu Niizuma, Masayuki Kanamori, Chikashi Nakanishi, Shinichi Yamashita, Toru Nakano, Teiji Tominaga

    Journal of neurological surgery. Part A, Central European neurosurgery 2022/10/17

    DOI: 10.1055/a-1962-1345  

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    Object Pulsed water jet is an emerging surgical instrumentation intended to achieve both maximal lesion resection and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The piezo actuator-driven pulsed water jet (ADPJ) is a new technology that can deliver a precisely controlled uniform and efficient pulsed water jet with minimum water flow. The present study evaluated the ADPJ system in preclinical animal studies in the swine brain, and investigated breaking strength, one of the parameters for mechanical properties, to elucidate the mechanism of tissue selectivity for tissue dissection by the water jet. Methods This system consisted of a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle (internal diameter: 0.15 mm). The water was supplied at 6 ml/min. The relationship between input voltage (3-25 V at 400 Hz) and peak pressure was measured using a pressure sensor through a sensing hole. Temporal profile of dissection depth during moving application was evaluated using gelatin brain phantom and swine brain. The dissected specimens were evaluated histologically. The mechanical property (breaking strength) of swine brain was measured by a compact table-top universal tester. Results Peak pressure increased linearly with increase in the input voltage, which reflected dissection depth in both the gelatin brain phantom and swine brain. Small arteries were preserved, and minimum damage to surrounding tissues occurred. The breaking strength of arachnoid membrane (0.12 ± 0.014 MPa) was significantly higher compared to gray matter (0.030 ± 0.010 MPa) and white matter (0.056 ± 0.009 MPa) (p < 0.05). The breaking strength of gray matter corresponded to that of 3 wt% gelatin, and that of white matter corresponded to a value between those of 3.5 and 4 wt% gelatin, and the dissection depth seemed to be estimated by 3-4 wt% gelatin. Conclusion The present study suggests that the ADPJ system has the potential to achieve accurate tissue dissection with preservation of blood vessels in neurosurgery. The difference in breaking strength may explain the tissue selectivity between brain parenchyma and tissue protected by the arachnoid membrane.

  22. くも膜下出血の病態 くも膜下出血後脳血管攣縮に対するクラゾセンタンの有効性

    遠藤 英徳, 新妻 邦泰, 冨永 悌二

    脳循環代謝 34 (1) 83-83 2022/10

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  23. Development and validation of machine learning prediction model for post-rehabilitation functional outcome after intracerebral hemorrhage

    Shinya Sonobe, Tetsuo Ishikawa, Kuniyasu Niizuma, Eiryo Kawakami, Takuya Ueda, Eichi Takaya, Carlos Makoto Miyauchi, Junya Iwazaki, Ryuzaburo Kochi, Toshiki Endo, Arun Shastry, Vijayananda Jagannatha, Ajay Seth, Atsuhiro Nakagawa, Masahiro Yoshida, Teiji Tominaga

    Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 29 2022/09

    DOI: 10.1016/j.inat.2022.101560  

    eISSN:2214-7519

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    Objective: Predicting outcomes after intracerebral hemorrhage (ICH) may help improve patient outcomes. We developed and validated a machine learning prediction model for post-rehabilitation functional outcomes after ICH. Patient selection and explanatory variable settings were based on clinical significance. Functional outcomes were predicted using ternary classification. Methods: The subjects were patients aged > 18 years without pre-onset severe disability who developed primary putaminal and/or thalamic hemorrhage and underwent an inpatient rehabilitation program. As explanatory variables, 43 values related to patient background, imaging-related findings, systemic conditions, neurological findings, and blood tests were acquired within 10 days of onset. As an objective variable, the functional outcome at discharge to home or nursing home was acquired using a ternary classification. The dataset consisting of the collected information was split into a training dataset and a test dataset with a ratio of 2:1. A predictive model using a balanced random forest algorithm was created using supervised learning from the training dataset. The predictive performance was validated using a test dataset. Results: Between January 2018 and June 2019, 100 consecutive patients were included in the study. The areas under the receiver operating characteristic curves for predictions of good, moderate, and poor outcomes were 0.952, 0.790, and 0.921, respectively. Conclusions: The predictive performance of the model was comparable to that of previous models. Patient selection and variable settings from a clinical perspective may contribute to accurate and detailed predictions. These study designs are based on design thinking and may meet the needs of clinical practice.

  24. Correction to: Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. International-journal

    Sosuke Kageyama, Atsuhiro Nakagawa, Tomohiro Kawaguchi, Kiyonobu Ohtani, Toshiki Endo, Manabu Kyan, Tetsuya Kusunoki, Yoshiteru Shimoda, Shin-Ichiro Osawa, Masayuki Kanamori, Kuniyasu Niizuma, Teiji Tominaga

    BMC research notes 15 (1) 279-279 2022/08/15

    DOI: 10.1186/s13104-022-06167-0  

  25. Codon usage and mRNA stability are translational determinants of cellular response to canonical ferroptosis inducers International-journal

    Sherif Rashad, Shane R Byrne, Daisuke Saigusa, Jingdong Xiang, Yuan Zhou, Liyin Zhang, Thomas J Begley, Teiji Tominaga, Kuniyasu Niizuma

    Neuroscience 501 103-130 2022/08

    Publisher: Elsevier BV

    DOI: 10.1016/j.neuroscience.2022.08.009  

    ISSN:0306-4522

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    Ferroptosis is a non-apoptotic cell death mechanism characterized by the generation of lipid peroxides. While many effectors in the ferroptosis pathway have been mapped, its epitranscriptional regulation is not yet fully understood. Ferroptosis can be induced via system xCT inhibition (Class I) or GPX4 inhibition (Class II). Previous works have revealed important differences in cellular response to different ferroptosis inducers. Importantly, blocking mRNA transcription or translation appears to protect cells against Class I ferroptosis inducing agents but not Class II. In this work, we examined the impact of blocking transcription (via Actinomycin D) or translation (via Cycloheximide) on Erastin (Class I) or RSL3 (Class II) induced ferroptosis. Blocking transcription or translation protected cells against Erastin but was detrimental against RSL3. Cycloheximide led to increased levels of GSH alone or when co-treated with Erastin via the activation of the reverse transsulfuration pathway. RNA sequencing analysis revealed early activation of a strong alternative splice program before observed changes in transcription. mRNA stability analysis revealed divergent mRNA stability changes in cellular response to Erastin or RSL3. Importantly, codon optimality biases were drastically different in either condition. Our data also implicated translation repression and rate as an important determinant of the cellular response to ferroptosis inducers. Given that mRNA stability and codon usage can be influenced via the tRNA epitranscriptome, we evaluated the role of a tRNA modifying enzyme in ferroptosis stress response. Alkbh1, a tRNA demethylase, led to translation repression and increased the resistance to Erastin but made cells more sensitive to RSL3.

  26. Plasma tRNA derivatives concentrations for detecting early brain damage in patients with acute large vessel occlusion and predicting clinical outcomes after endovascular thrombectomy. International-journal

    Tomohisa Ishida, Takashi Inoue, Kuniyasu Niizuma, Tomoo Inoue, Keisuke Sasaki, Hiroyuki Sakata, Masayuki Ezura, Hiroshi Uenohara, Takaaki Abe, Teiji Tominaga

    Clinical neurology and neurosurgery 220 107358-107358 2022/07/01

    DOI: 10.1016/j.clineuro.2022.107358  

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    OBJECTIVE: Transfer RNA (tRNA) is involved in the acute stress response, which results in conformational changes and subsequent fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine, we can selectively detect blood tRNA derivatives from damaged tissues, including neuronal tissue, which serves as a potential marker of early tissue damage. This preliminary study aimed to investigate the correlation between tRNA derivatives and clinical outcomes in patients with acute anterior large vessel occlusion, especially those who underwent endovascular thrombectomy (EVT). METHODS: Patients with acute ischemic stroke due to anterior circulation large vessel occlusion were prospectively enrolled in this study. Plasma tRNA derivatives were measured using an enzyme-linked immunosorbent assay with an anti-modified nucleoside 1-methyladenosine antibody. RESULTS: Seventeen patients were included. The plasma tRNA derivatives concentrations on admission increased significantly, corresponding to the infarction size (r = 0.492, p = 0.038), and were associated with clinical outcomes (p = 0.00309). A good clinical outcome (90-day modified Rankin scale score: 0-2) was achieved in seven patients (41.2%), and all had undergone EVT. Among these patients, tRNA derivatives concentrations were the only preoperative predictor, which was associated with good outcomes (modified Rankin scale score: 0-2) and was significantly lower than those with poor outcomes (modified Rankin scale score: 3-6) (p = 0.0333). Receiver operating characteristic analysis revealed that a tRNA derivative value of ≤ 142.0 mg/mL was associated with good clinical outcomes, with a sensitivity of 85.7% and a specificity of 100% (area under the curve, 0.952; 95% confidence interval: 0.82-1). CONCLUSION: tRNA derivatives concentration may be a sensitive marker of early brain damage in patients with acute large vessel occlusion. Patients with low levels of tRNA derivatives on arrival are likely to benefit from thrombectomy and have the potential to achieve good clinical outcomes.

  27. RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses. International-journal

    Liyin Zhang, Sherif Rashad, Yuan Zhou, Kuniyasu Niizuma, Teiji Tominaga

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 42 (11) 271678X221110679-2122 2022/06/25

    DOI: 10.1177/0271678X221110679  

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    RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.

  28. 高拍出性心不全を呈し血管内治療を行った新生児2例

    熊井 萌, 君和田 友美, 佐藤 健一, 新妻 邦泰, 林 俊哲, 萩野 有正, 渡邉 達也, 室月 淳, 菊地 千歌, 五十嵐 あゆ子, 木村 正人, 田中 高志, 冨永 悌二

    小児の脳神経 47 (2) 242-242 2022/04

    Publisher: (一社)日本小児神経外科学会

    ISSN:0387-8023

    eISSN:2435-824X

  29. Effects of clazosentan on cerebral vasospasm-related morbidity and all-cause mortality after aneurysmal subarachnoid hemorrhage: two randomized phase 3 trials in Japanese patients. International-journal

    Hidenori Endo, Yasushi Hagihara, Naoto Kimura, Katsumi Takizawa, Kuniyasu Niizuma, Osamu Togo, Teiji Tominaga

    Journal of neurosurgery 137 (6) 1-11 2022/04/01

    DOI: 10.3171/2022.2.JNS212914  

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    OBJECTIVE: Clazosentan has been investigated globally for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). The authors evaluated its effects on vasospasm-related morbidity and all-cause mortality following aSAH in Japanese patients. METHODS: Two similar double-blind, placebo-controlled phase 3 studies were conducted in 57 Japanese centers in patients with aSAH, after aneurysms were secured by endovascular coiling in one study and surgical clipping in the other. In each study, patients were randomly administered intravenous clazosentan (10 mg/hr) or placebo (1:1) starting within 48 hours of aSAH and for up to 15 days after aSAH. Stratified randomization based on World Federation of Neurosurgical Societies grade was performed using a centralized interactive web response system. Vasospasm-related morbidity and all-cause mortality within 6 weeks post-aSAH, including new cerebral infarcts and delayed ischemic neurological deficits as well as all-cause mortality, were the first primary endpoint in each study. The second primary endpoint was all-cause morbidity (new cerebral infarct or delayed ischemic neurological deficit from any causes) and all-cause mortality (all-cause morbidity/mortality) within 6 weeks post-aSAH. The incidence of individual components of the primary morbidity/mortality endpoints within 6 weeks and patient outcome at 12 weeks post-aSAH (including the modified Rankin Scale scores) were also evaluated. The above analyses were also performed in the population pooled from both studies. RESULTS: In each study, 221 patients were randomized and 220 were included in the full analysis set of the primary analysis (109 in each clazosentan group, 111 in each placebo group). Clazosentan significantly reduced the incidence of vasospasm-related morbidity and all-cause mortality after aneurysm coiling (from 28.8% to 13.6%; relative risk reduction 53%; 95% CI 17%-73%) and after clipping (from 39.6% to 16.2%; relative risk reduction 59%; 95% CI 33%-75%). All-cause morbidity/mortality and poor outcome (dichotomized modified Rankin Scale scores) were significantly reduced by clazosentan after preplanned study pooling. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan significantly reduced the combined incidence of vasospasm-related morbidity and all-cause mortality post-aSAH with no unexpected safety findings. Clinical trial registration nos.: JapicCTI-163368 and JapicCTI-163369 (https://www.clinicaltrials.jp).

  30. Morphological comparison of masseter muscle fibers in the mandibular rest and open positions using diffusion tensor imaging. International-journal

    Takehiko Sugano, Toru Ogawa, Nobuhiro Yoda, Teruo Hashimoto, Kenta Shobara, Kuniyasu Niizuma, Ryuta Kawashima, Keiichi Sasaki

    Journal of oral rehabilitation 49 (6) 608-615 2022/03/25

    DOI: 10.1111/joor.13319  

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    BACKGROUND: The masseter muscle has a complicated multipennate internal structure and exhibits functional differentiation when performing various stomatognathic functions. It is important to understand the internal structural changes of the muscle during functioning to elucidate characteristic muscle disorders such as local myalgia. Diffusion tensor imaging (DTI) may be useful for investigating the internal structural features of muscle. OBJECTIVES: To evaluate the features of masseter muscle fibers in human participants using DTI fiber tractography, and to elucidate the structural differences in the masseter muscle between the mandibular rest and open positions. METHODS: Five healthy men (age 31±7 years) underwent DTI and T1-weighted MRI of the right masseter muscle in the mandibular rest and open positions. MR images were used as a reference for muscle layer segmentation (superficial, intermediate, and deep). DTI fiber tractography of the masseter muscle was performed and the orientation of the DTI fibers was analyzed in each layer using coordinates based on the Frankfurt horizontal plane. RESULTS: The DTI fiber orientation of the deep layer significantly changed between the mandibular rest and open positions in the frontal plane (p<0.05, Wilcoxon rank sum test). However, no significant change was found in the superficial and intermediate layers. CONCLUSION: DTI fiber tractography confirmed regional differences in the orientation change of the masseter muscle fibers between different mandibular positions. The results may support the existence of functional partitioning inside the masseter muscle and suggest that DTI may be useful for the evaluation of muscle fibers in multipennate muscles.

  31. Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. International-journal

    Sosuke Kageyama, Atsuhiro Nakagawa, Tomohiro Kawaguchi, Kiyonobu Ohtani, Toshiki Endo, Manabu Kyan, Tetsuya Kusunoki, Yoshiteru Shimoda, Shin-Ichiro Osawa, Masayuki Kanamori, Niizuma Kuniyasu, Teiji Tominaga

    BMC research notes 15 (1) 85-85 2022/03/02

    DOI: 10.1186/s13104-022-05947-y  

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    OBJECTIVE: We developed an actuator-driven pulsed water jet (ADPJ) device to achieve maximal lesion dissection with minimal risk of normal structural damage. Despite the unique dissection characteristics, there is a risk of dissemination of tissue dispersion; however, there is no established method to quantify the dispersion. Hence, this study aimed to assess the factors associated with dispersion and propose a simple experimental method using spectrophotometry to evaluate the degree of dispersion in a wet field. RESULTS: Methylene blue-stained brain phantom gelatin was immersed in a chamber with distilled water solution and dissected with an ADPJ. The dispersed gelatin solution was stirred and warmed to dissolve. The absorbance of the solution was measured spectrophotometrically. First, a reference standard curve was constructed to confirm the relationship between the absorbance and the amount of the dispersed gelatin. A clear proportional correlation was observed, which indicated that absorbance measurements can help evaluate the amount of dispersion. Using this method, we revealed that a high dissection force, insufficient suction, and inappropriate long distance between the nozzle tip and the target were associated with increased dispersion. This method might constitute a versatile and reliable approach to evaluate dispersion and aid in the development of surgical devices.

  32. 超選択的Wada Testにおける片麻痺に対する病態失認の検討

    細川 大瑛, 大沢 伸一郎, 柿沼 一雄, 太田 祥子, 親富祖 まりえ, 浮城 一司, 石田 誠, 神 一敬, 中里 信和, 新妻 邦泰, 冨永 悌二, 鈴木 匡子

    高次脳機能研究 42 (1) 71-72 2022/03

    Publisher: (一社)日本高次脳機能障害学会

    ISSN:1348-4818

    eISSN:1880-6554

  33. 言語症状に対する内観と失語型との対応 超選択的Wadaテストによる検討

    柿沼 一雄, 大沢 伸一郎, 細川 大瑛, 親富祖 まりえ, 太田 祥子, 浮城 一司, 石田 誠, 神 一敬, 中里 信和, 新妻 邦泰, 冨永 悌二, 鈴木 匡子

    高次脳機能研究 42 (1) 97-97 2022/03

    Publisher: (一社)日本高次脳機能障害学会

    ISSN:1348-4818

    eISSN:1880-6554

  34. 超選択的Wada Testにおける片麻痺に対する病態失認の検討

    細川 大瑛, 大沢 伸一郎, 柿沼 一雄, 太田 祥子, 親富祖 まりえ, 浮城 一司, 石田 誠, 神 一敬, 中里 信和, 新妻 邦泰, 冨永 悌二, 鈴木 匡子

    高次脳機能研究 42 (1) 71-72 2022/03

    Publisher: (一社)日本高次脳機能障害学会

    ISSN:1348-4818

    eISSN:1880-6554

  35. Application of Diffusion Tensor Imaging Fiber Tractography for Human Masseter Muscle.

    Takehiko Sugano, Nobuhiro Yoda, Toru Ogawa, Teruo Hashimoto, Kenta Shobara, Kuniyasu Niizuma, Ryuta Kawashima, Keiichi Sasaki

    The Tohoku journal of experimental medicine 256 (2) 151-160 2022/02

    DOI: 10.1620/tjem.256.151  

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    Diffusion tensor imaging (DTI) has been used to indicate the direction of nerve and muscle fibers by using the characteristics that water molecules preferentially diffuse along the fibrous structure. However, DTI fiber tractography for multipennate muscles, such as the masseter muscle, is challenging due to a lack of data regarding the imaging parameters. This study aimed to determine the optimal DTI parameters for masseter muscle fiber tractography. A 27-year-old healthy man voluntarily underwent DTI and T1-weighted magnetic resonance imaging of the right masseter muscle. Four imaging parameter settings were created by combining the following parameters that particularly affect the signal-to-noise ratio: b-value, number of excitations (NEX), and number of motion probing gradient (MPG) directions. DTI fiber tractography was performed using specific software for each parameter setting. The length and orientation of the muscle fibers in each layer were calculated. As a result, the masseter muscle fibers of each layer were identified on DTI. Although the detected fiber length was affected significantly by the imaging parameters, the fiber orientation was insignificantly affected. The appropriate combination of the b-value, NEX, and the number of MPG directions for masseter muscle fiber tractography could be determined based on previously reported anatomical data of the masseter muscle fibers. DTI may enable the non-invasive evaluation of masseter muscle fiber length and orientation. Elucidation of the details of masseter muscle fiber orientation is useful in evaluating stomatognathic biomechanics and muscle disorders.

  36. Wall enhancement in unruptured posterior communicating aneurysms with oculomotor nerve palsy on magnetic resonance vessel wall imaging. International-journal

    Shunsuke Omodaka, Hidenori Endo, Kuniyasu Niizuma, Toshiki Endo, Kenichi Sato, Atsushi Saito, Hiroki Uchida, Yasushi Matsumoto, Teiji Tominaga

    Journal of neurosurgery 1-7 2022/01/21

    DOI: 10.3171/2021.11.JNS212249  

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    OBJECTIVE: Recent MR vessel wall imaging studies of unruptured intracranial aneurysms (UIAs) have revealed that aneurysm wall enhancement (AWE) can be an indicator for aneurysm evolution; however, the degree of AWE among different types of evolving UIAs has yet to be clarified. The authors assessed the degree of AWE in unruptured posterior communicating artery (PcomA) aneurysms with oculomotor nerve palsy (ONP), which may be a subgroup of evolving UIAs with rapid enlargement and high rupture risk. METHODS: The degree of AWE was analyzed in 35 consecutive evolving PcomA aneurysms (19 with and 16 without ONP). UIAs were considered to be evolving when showing growth or ONP. A 3D T1-weighted fast spin echo sequence was obtained after contrast media injection, and the contrast ratio of the aneurysm wall against the pituitary stalk (CRstalk) was calculated as the indicator of AWE. The CRstalk in evolving UIAs with ONP was compared with that in UIAs without ONP. RESULTS: The CRstalk was significantly higher in evolving UIAs with ONP than in those without ONP (0.85 vs 0.57; p = 0.006). In multivariable analysis, the CRstalk remained a significant indicator for ONP presentation in evolving UIAs (OR 6.13, 95% CI 1.21-31.06). CONCLUSIONS: AWE was stronger in evolving PcomA aneurysms with ONP than in those without ONP, suggesting the potential utility of AWE for risk stratification in evolving UIAs. The degree of AWE can be a promising indicator of a rupture-prone UIA, which can be useful information for the decision-making process in the treatment of UIAs.

  37. Quantitative assessment of microstructural evolution of intracranial aneurysm wall by vessel wall imaging. International-journal

    Hidenori Endo, Naoko Mori, Shunji Mugikura, Kuniyasu Niizuma, Shunsuke Omodaka, Kei Takase, Teiji Tominaga

    Neuroradiology 64 (7) 1343-1350 2022/01/08

    DOI: 10.1007/s00234-021-02877-7  

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    PURPOSE: This study aimed to evaluate new quantitative parameters of aneurysm wall enhancement (AWE) on magnetic resonance vessel wall imaging (VWI) in differentiating between the stable and evolving unruptured intracranial aneurysms (UIAs). METHODS: Thirty-eight consecutive patients with UIAs (27 stable and 11 evolving) underwent VWI with contrast-enhanced 3D T1 volume isotropic turbo spin echo acquisition. The voxel-based enhancement maps were created using pre- and post-contrast images. The aneurysmal lumen with signal suppression by black-blood method was segmented. Then, one voxel outer and inner layers of the lumen contour were automatically segmented. The shape features of the aneurysms and AWE of the two layers were compared between stable and evolving groups. RESULTS: The shape features, including aneurysm volume, surface, and compacity were significantly different between the stable and evolving groups (P = 0.024, 0.028, and 0.033, respectively). Stable and evolving groups also differed significantly in the AWE at the union of outer and inner layers of the aneurysm wall (P = 0.0082) but not in that of the outer or inner layer alone. Multivariate logistic regression analysis revealed significant differences in aneurysm volume, surface, and AWE at the union of outer and inner layers between the two groups (P = 0.0029, 0.0092, and 0.0033, respectively). Receiver operating characteristics curve analysis revealed that the area under the curve of the logistic regression model was 0.89. CONCLUSION: Quantitative combined analysis of aneurysm shape features and AWE of the union of outer and inner layers were effective for differentiating between stable and evolving UIAs.

  38. Efficacy of ultra-high-resolution computed tomographic angiography for postoperative evaluation of intracranial aneurysm after clipping surgery: A case report. International-journal

    Shingo Kayano, Akira Ito, Toshiki Endo, Hitoshi Nemoto, Kazuki Shimada, Kuniyasu Niizuma, Teiji Tominaga

    Surgical neurology international 13 85-85 2022

    DOI: 10.25259/SNI_1190_2021  

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    Background: Following clipping surgery for intracranial aneurysm, computed tomography angiography (CTA) is often used to confirm complete aneurysm obliteration. However, artifacts from the titanium clips usually degrade the images around them. The ultra-high-resolution computed tomography (UHR-CT) system recently became available in clinical practice. Here, we report a case in which CTA using the UHR-CT system successfully pointed out a small aneurysmal remnant after the clipping surgery, which was validated by digital subtraction angiography. Case Description: A patient underwent clipping surgery for an unruptured aneurysm using two titanium alloy clips. CTA using the UHR-CT system demonstrated a small remnant aneurysm. Digital subtraction angiography confirmed the minor remnant. The UHR-CTA images were comparable to three-dimensional reconstructed images from the rotational angiography. Conclusion: We propose that UHR-CTA is a reliable postoperative assessment method for intracranial clipping surgeries.

  39. Carotid computed tomography angiography after cobalt-based alloy carotid artery stenting using ultra-high-resolution computed tomography with model-based iterative reconstruction. International-journal

    Shingo Kayano, Hideki Ota, Yoshimichi Sato, Toshiki Endo, Kuniyasu Niizuma, Ichiro Suzuki, Tsuyoshi Kawamura, Kei Takase

    Radiology case reports 16 (12) 3721-3728 2021/12

    DOI: 10.1016/j.radcr.2021.09.003  

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    In conventional carotid computed tomographic angiography, the artifacts of the stent vary depending on the structure and characteristics of the alloy type. Cobalt-based alloy stents have been reported to exhibit high artifacts, and accurate evaluation of the internal lumen can be difficult. Recently, ultra-high-resolution computed tomography scanner systems have become available for clinical practice. The primary features of this computed tomography scanner are a 0.25-mm detector row width and a 1024 × 1024 matrix. We report a case-series of carotid artery stenting using a cobalt-based alloy stent scanned by an ultra-high-resolution computed tomography scanner system and model-based iterative reconstruction. We also report that the combination of the ultra-high-resolution computed tomography scanner system with model-based iterative reconstruction would be useful to evaluate vessel patency after placement of a cobalt-based alloy stent.

  40. Intraoperative motor-evoked potential monitoring during coil embolization for anterior choroidal artery aneurysms. International-journal

    Akira Ito, Kenichi Sato, Kuniyasu Niizuma, Hidenori Endo, Yasushi Matsumoto, Teiji Tominaga

    Neuroradiology 64 (6) 1221-1229 2021/11/17

    DOI: 10.1007/s00234-021-02847-z  

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    PURPOSE: Intraoperative motor-evoked potential (MEP) monitoring is widely used in the neck clipping of cerebral aneurysms. Little is known regarding the usefulness of intraoperative MEP monitoring in endovascular aneurysm surgery. The purpose of this study was to validate the feasibility of intraoperative MEP monitoring during the coil embolization of anterior choroidal artery (AChA) aneurysms. METHODS: Clinical and angiographic data of consecutive patients who underwent coil embolization for unruptured AChA aneurysms with or without intraoperative MEP monitoring between January 2014 and December 2018 at our institute were abstracted and analyzed retrospectively. RESULTS: Twenty-three unruptured AChA aneurysms were treated. Eleven patients received MEP monitoring, and three of them experienced intraoperative reduction or disappearance of the MEP wave. Even during MEP changes, AChA filling showed no change in any of the three cases. Although one case with MEP monitoring encountered the disappearance of AChA filling, there was no change in MEP. This might be due to retrograde filling of the AChA from the anastomosis with the lateral posterior choroidal artery. AChA blood flow detected by angiography did not always reflect MEP status. When comparing the presence or absence of MEP monitoring, the volume embolization ratio of coiled aneurysms was significantly better in the MEP group. CONCLUSION: Intraoperative MEP monitoring during endovascular coiling for AChA aneurysms may be feasible. AChA blood flow detected by angiography does not always reflect MEP status.

  41. 麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    脳血管内治療 6 (Suppl.) S337-S337 2021/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  42. 未破裂脳動脈瘤におけるVessel wall imagingの新規定量評価法

    遠藤 英徳, 森 菜緒子, 麦倉 俊司, 新妻 邦泰, 面高 俊介, 高瀬 圭, 冨永 悌二

    脳血管内治療 6 (Suppl.) S39-S39 2021/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  43. 麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    脳血管内治療 6 (Suppl.) S337-S337 2021/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  44. Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease. International-journal

    Dan Ozaki, Hidenori Endo, Ryosuke Tashiro, Koichiro Sugimura, Shunsuke Tatebe, Satoshi Yasuda, Yasutake Tomata, Toshiki Endo, Keita Tominaga, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland) 51 (3) 1-6 2021/10/28

    DOI: 10.1159/000519717  

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    BACKGROUND: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. METHODS: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. RESULTS: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. CONCLUSIONS: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.

  45. 頭蓋内動脈への超選択的麻酔薬注入による詳細な神経症状評価と手術適応への寄与

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学 49 (5) 449-449 2021/10

    Publisher: (一社)日本臨床神経生理学会

    ISSN:1345-7101

    eISSN:2188-031X

  46. 頭蓋内動脈への超選択的麻酔薬注入による詳細な神経症状評価と手術適応への寄与

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 新妻 邦泰, 下田 由輝, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学 49 (5) 449-449 2021/10

    Publisher: (一社)日本臨床神経生理学会

    ISSN:1345-7101

    eISSN:2188-031X

  47. Computational hemodynamic analysis of the offending vertebral artery at the site of neurovascular contact in a case of hemifacial spasm associated with subclavian steal syndrome: illustrative case. International-journal

    Keita Tominaga, Hidenori Endo, Shin-Ichiro Sugiyama, Shin-Ichiro Osawa, Kuniyasu Niizuma, Teiji Tominaga

    Journal of neurosurgery. Case lessons 2 (12) CASE21447 2021/09/20

    DOI: 10.3171/CASE21447  

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    BACKGROUND: Hemifacial spasm (HFS) is caused by neurovascular contact along the facial nerve's root exit zone (REZ). The authors report a rare HFS case that was associated with ipsilateral subclavian steal syndrome (SSS). OBSERVATIONS: A 42-year-old man with right-sided aortic arch presented with progressing left HFS, which was associated with ipsilateral SSS due to severe stenosis of the left brachiocephalic trunk. Magnetic resonance imaging showed contact between the left REZ and vertebral artery (VA), which had shifted to the left. The authors speculated that the severe stenosis at the left brachiocephalic trunk resulted in the left VA's deviation, which was the underlying cause of the HFS. The authors performed percutaneous angioplasty (PTA) to dilate the left brachiocephalic trunk. Ischemic symptoms of the left arm improved after PTA, but the HFS remained unchanged. A computational fluid dynamics study showed that the high wall shear stress (WSS) around the site of neurovascular contact decreased after PTA. In contrast, pressure at the point of neurovascular contact increased after PTA. LESSONS: SSS is rarely associated with HFS. Endovascular treatment for SSS reduced WSS of the neurovascular contact but increased theoretical pressure of the neurovascular contact. Physical release of the neurovascular contact is the best treatment option for HFS.

  48. Prediction of atherosclerotic changes in cavernous carotid aneurysms based on computational fluid dynamics analysis: a proof-of-concept study. International-journal

    Shintaro Nakajima, Shinichiro Sugiyama, Hidenori Oishi, Kenichi Sato, Yasushi Matsumoto, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    Neuroradiology 64 (3) 575-585 2021/09/09

    DOI: 10.1007/s00234-021-02803-x  

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    PURPOSE: Recent computational fluid dynamics (CFD) studies have demonstrated the concurrence of atherosclerotic changes in regions exposed to prolonged blood residence. In this proof-of-concept study, we investigated a small but homogeneous cohort of large, cavernous carotid aneurysms (CCAs) to establish the clinical feasibility of CFD analysis in treatment planning, based on the association between pathophysiology and hemodynamics. METHODS: This study included 15 patients with individual large CCAs. We identified calcifications, which indicated atherosclerotic changes, using the masking data of digital subtraction angiography. We conducted a CFD simulation under patient-specific inlet flow rates measured using magnetic resonance (MR) velocimetry. In the post-CFD analysis, we calculated the blood residence time ([Formula: see text]) and segmented the surface exposed to blood residence time over 1 s ([Formula: see text]). We measured the decrease in volume after flow diversion using the original time-of-flight MR angiography data. RESULTS: Calcifications were observed in the region with [Formula: see text]. In addition, the ratio of [Formula: see text] to the surface of the aneurysmal domain exhibited a negative relationship with the rate of volume reduction at the 6- and 12-month follow-ups. Post-CFD visualization demonstrated that intra-aneurysmal swirling flow prolonged blood residence time under the condition of a small inlet flow rate, when compared to the aneurysmal volume. CONCLUSION: The results of this study suggest the usefulness of CFD analysis for the diagnosis of atherosclerotic changes in large CCAs that may affect the therapeutic response after flow diversion.

  49. A Super-selective Wada Test Successfully Detected an Artery That Supplied Broca's Area in a Case of Left Frontal Lobe Glioblastoma: Technical Case Report.

    Shota Yamashita, Ryuta Saito, Shin-Ichiro Osawa, Kuniyasu Niizuma, Kazushi Ukishiro, Masayuki Kanamori, Kazuo Kakinuma, Kyoko Suzuki, Teiji Tominaga

    Neurologia medico-chirurgica 61 (11) 661-666 2021/08/26

    DOI: 10.2176/nmc.tn.2021-0054  

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    In cases of malignant gliomas located at language eloquent area, it is often difficult to preoperatively detect those area with functional MRI. Awake surgery is often used to spare the language eloquent area during surgery for such tumors; it is not available for a patient whose intracranial pressure is elevated due to the malignant tumor. The Wada test involves infusing anesthetic agents into the internal carotid artery to determine language dominancy before surgery for epilepsy or brain tumor. The super-selective Wada test is a technique to detect more detailed functional localization by infusing anesthetics into far distal middle cerebral artery branches. We present a 37-year-old man suffering from a left frontal lobe glioblastoma, in whom detection of an artery supplying Broca's area was attempted by a super-selective Wada test. The super-selective Wada test successfully detected the branch of middle cerebral artery supplying Broca's area. Total resection of the contrast-enhancing area was achieved without damaging the artery supplying Broca's area without any neurological sequelae. This is the first report describing the usefulness of the super-selective Wada test in glioblastoma treatment. Our findings suggest that the super-selective Wada test is a powerful and useful means to distinguish the artery that supplies the language area from the tumor feeding artery in cases of tumors in the language eloquent area.

  50. Digital intravascular pressure wave recording during endovascular treatment reveals abnormal shunting flow in vertebral venous fistula of the vertebral artery: illustrative case. International-journal

    Yoshiteru Shimoda, Shinya Sonobe, Kuniyasu Niizuma, Toshiki Endo, Hidenori Endo, Mayuko Otomo, Teiji Tominaga

    Journal of neurosurgery. Case lessons 2 (2) CASE21172 2021/07/12

    DOI: 10.3171/CASE21172  

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    BACKGROUND: An arteriovenous fistula is an abnormal arteriovenous shunt between an artery and a vein, which often leads to venous congestion in the central nervous system. The blood flow near the fistula is different from normal artery flow. A novel method to detect the abnormal shunting flow or pressure near the fistula is needed. OBSERVATIONS: A 76-year-old woman presented to the authors' institute with progressive right upper limb weakness. Right vertebral angiography showed a fistula between the right extracranial vertebral artery (VA) and the right vertebral venous plexus at the C7 level. The patient underwent endovascular treatment for shunt flow reduction. Before the procedure, blood pressures were measured at the proximal VA, distal VA near the fistula, and just at the fistula and drainer using a microcatheter. The blood pressure waveforms were characteristically different in terms of resistance index, half-decay time, and appearance of dicrotic notch. The fistula was embolized with coils and N-butyl cyanoacrylate solution. LESSONS: During endovascular treatment, the authors were able to digitally record the vascular pressure waveform from the tip of the microcatheter and succeeded in calculating several parameters that characterize the shunting flow. Furthermore, these parameters could help recognize the abnormal blood flow, allowing a safer endovascular surgery.

  51. Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation. International-journal

    Ryosuke Tashiro, Kuniyasu Niizuma, Jun Kasamatsu, Yuko Okuyama, Sherif Rashad, Atsuo Kikuchi, Miki Fujimura, Shigeo Kure, Naoto Ishii, Teiji Tominaga

    Journal of cellular physiology 236 (11) 7554-7564 2021/05/10

    DOI: 10.1002/jcp.30396  

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    Growing evidence suggest the association between Moyamoya disease (MMD) and immune systems, such as antigen presenting cells in particular. Rnf213 gene, a susceptibility gene for MMD, is highly expressed in immune tissues, however, its function remains unclear. In addition, the physiological role of RNF213 gene polymorphism c.14576G > A (rs112735431), susceptibility variant for MMD, is also poorly understood. By studying Rnf213-knockout (Rnf213-KO) mice with deletion of largest exon32 and Rnf213-knockin (Rnf213-KI) mice with insertion of single-nucleotide polymorphism corresponding to c.14576G > A mutation in MMD patients, we aimed to investigate the role of RNF213 in dendritic cell development, and antigen processing and presentation. First, we found a high level of Rnf213 gene expression in conventional DCs and monocytes. Second, flow cytometric and confocal microscopic analysis revealed ovalbumin protein-pulsed Rnf213-KO and Rnf213-KI DCs showed impaired antigen uptake, proteolysis and reduced numbers of endosomes and lysosomes, and thereby failed to activate and proliferate antigen-specific T cells efficiently. In addition, Rnf213-KI DCs showed a similar phenotype to that of Rnf213-KO BMDCs. In conclusion, our findings suggest the critical role of RNF213 in antigen uptake, processing and presentation.

  52. エンボスフィアを用いた経動脈的塞栓で根治し得た海綿静脈洞部硬膜動静脈瘻の1例

    陳 梦格, 大沢 伸一郎, 新妻 邦泰, 遠藤 英徳, 冨永 悌二

    脳血管内治療 6 (1) 38-43 2021/05

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

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    【目的】硬膜動静脈瘻(dAVF)の経静脈的塞栓(TVE)困難症例に対し,脳神経栄養枝を持つ親動脈からエンボスフィアによる経動脈的塞栓(TAE)を行い,合併症なく長期のシャント完全閉塞を得た症例を報告する.【症例】74歳,女性.結膜充血と外転神経麻痺で発症し,精査で左海綿静脈洞部dAVFと診断した.TVEは内頸静脈閉塞によりアクセス困難で断念し,次善策としてTAEを試み,中硬膜動脈の錐体枝分岐近位からφ300〜500μmエンボスフィアを注入して合併症なくシャント閉塞を得た.4年間再発なく経過している.【結論】エンボスフィアを用いたTAEは,脳神経栄養枝を含む血管の塞栓術において選択肢となり得る.(著者抄録)

  53. エンボスフィアを用いた経動脈的塞栓で根治し得た海綿静脈洞部硬膜動静脈瘻の1例

    陳 梦格, 大沢 伸一郎, 新妻 邦泰, 遠藤 英徳, 冨永 悌二

    脳血管内治療 6 (1) 38-43 2021/05

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

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    【目的】硬膜動静脈瘻(dAVF)の経静脈的塞栓(TVE)困難症例に対し,脳神経栄養枝を持つ親動脈からエンボスフィアによる経動脈的塞栓(TAE)を行い,合併症なく長期のシャント完全閉塞を得た症例を報告する.【症例】74歳,女性.結膜充血と外転神経麻痺で発症し,精査で左海綿静脈洞部dAVFと診断した.TVEは内頸静脈閉塞によりアクセス困難で断念し,次善策としてTAEを試み,中硬膜動脈の錐体枝分岐近位からφ300〜500μmエンボスフィアを注入して合併症なくシャント閉塞を得た.4年間再発なく経過している.【結論】エンボスフィアを用いたTAEは,脳神経栄養枝を含む血管の塞栓術において選択肢となり得る.(著者抄録)

  54. The cell and stress-specific canonical and noncanonical tRNA cleavage. International-journal

    Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cellular physiology 236 (5) 3710-3724 2021/05

    DOI: 10.1002/jcp.30107  

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    Following stress, transfer RNA (tRNA) is cleaved to generate tRNA halves (tiRNAs). These tiRNAs have been shown to repress protein translation. Angiogenin was considered the main enzyme that cleaves tRNA at its anticodon to generate 35-45 nucleotide long tiRNA halves, however, the recent reports indicate the presence of angiogenin-independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anticodon site. To explore this noncanonical cleavage, we analyze tRNA cleavage patterns in rat model of ischemia-reperfusion and in two rat cell lines. In vivo mitochondrial tRNAs were prone to this noncanonical cleavage pattern. In vitro, however, cytosolic and mitochondrial tRNAs could be cleaved noncanonically. Our results show an important regulatory role of mitochondrial stress in angiogenin-mediated tRNA cleavage. Neither angiogenin nor RNH1 appear to regulate the noncanonical tRNA cleavage. Finally, we verified our previous findings of the role of Alkbh1 in regulating tRNA cleavage and its impact on noncanonical tRNA cleavage.

  55. Effect of endoscope flexibility on tissue dissection profile assessed with pulsed water jet device: ensuring safety, efficacy, and handling of thin devices for neuroendoscopic surgery. International-journal

    Tetsuya Kusunoki, Tomohiro Kawaguchi, Atsuhiro Nakagawa, Yuta Noguchi, Shin-Ichiro Osawa, Hidenori Endo, Toshiki Endo, Ryuta Saito, Masayuki Kanamori, Kuniyasu Niizuma, Teiji Tominaga

    BMC research notes 14 (1) 64-64 2021/02/17

    DOI: 10.1186/s13104-021-05475-1  

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    OBJECTIVE: We developed an actuator-driven pulsed water jet device (ADPJ) for flexible neuroendoscopy to achieve effective tissue dissection with vasculature preservation. Although flexibility is a strong advantage for minimally invasiveness, the effect of the ductile curvature on the dissection profiles remains unknown. The purpose of this study was to clarify the impact of the curvature change of the ADPJ connecting tube on the dissection safety and efficacy. RESULTS: Three ADPJ connecting tubes with different inner diameters (1.0, 0.75, 0.5 mm) were used to dissect the brain phantom. They were bent at 3 angles: 0°, 60°, and 120°. The dissection profiles were evaluated using the mean depth and coefficient of variation (CV) for efficacy and safety, respectively.The larger inner diameter connecting tube dissected more deeply. The dissection depth was not changed regardless of the curvature degree in each tube. There was no significant difference in CVs regardless of inner diameter and curvature. The ductile curvature of the flexible neuroendoscope did not affect the efficacy and safety of the ADPJ dissection profile. Among the numerous instruments, tube-formed devices, including suction and injecting devices such as ADPJ, can be used safely and effectively without flexibility-related limitations.

  56. Brain Temperature Measured by Magnetic Resonance Spectroscopy to Predict Clinical Outcome in Patients with Infarction. International-journal

    Tomohisa Ishida, Takashi Inoue, Tomoo Inoue, Toshiki Endo, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

    Sensors (Basel, Switzerland) 21 (2) 2021/01/12

    DOI: 10.3390/s21020490  

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    Acute ischemic stroke is characterized by dynamic changes in metabolism and hemodynamics, which can affect brain temperature. We used proton magnetic resonance (MR) spectroscopy under everyday clinical settings to measure brain temperature in seven patients with internal carotid artery occlusion to explore the relationship between lesion temperature and clinical course. Regions of interest were selected in the infarct area and the corresponding contralateral region. Single-voxel MR spectroscopy was performed using the following parameters: 2000-ms repetition time, 144-ms echo time, and 128 excitations. Brain temperature was calculated from the chemical shift between water and N-acetyl aspartate, choline-containing compounds, or creatine phosphate. Within 48 h of onset, compared with the contralateral region temperature, brain temperature in the ischemic lesion was lower in five patients and higher in two patients. Severe brain swelling occurred subsequently in three of the five patients with lower lesion temperatures, but in neither of the two patients with higher lesion temperatures. The use of proton MR spectroscopy to measure brain temperature in patients with internal carotid artery occlusion may predict brain swelling and subsequent motor deficits, allowing for more effective early surgical intervention. Moreover, our methodology allows for MR spectroscopy to be used in everyday clinical settings.

  57. Comparison between ultra-high-resolution computed tomographic angiography and conventional computed tomographic angiography in the visualization of the subcallosal artery. International-journal

    Yoshimichi Sato, Toshiki Endo, Shingo Kayano, Hitoshi Nemoto, Kazuki Shimada, Akira Ito, Hidenori Endo, Shunji Mugikura, Kuniyasu Niizuma, Teiji Tominaga

    Surgical neurology international 12 528-528 2021

    DOI: 10.25259/SNI_887_2021  

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    Background: The subcallosal artery (ScA) is a single dominant artery arising from the anterior communicating artery. Its injury causes amnesia and cognitive disturbance. The conventional computed tomographic angiography (C-CTA) is a common evaluation method of the intracranial artery. However, to image tinny perforating arteries such as the ScA is technically demanding for C-CTA. The purpose of this study is to investigate whether the ultra-high-resolution CTA (UHR-CTA) could image the ScA better than C-CTA. UHR-CTA became available in clinical practice in 2017. Its novel features are the improvement of the detector system and a small X-ray focus. Methods: Between April 2019 and May 2020, 77 and 49 patients who underwent intracranial UHR-CTA and C-CTA, respectively, were enrolled in this study. Two board-certified neurosurgeons participated as observers to identify the ScA based on UHR-CTA and C-CTA images. Results: UHR-CTA and C-CTA detected the ScA in 56-58% and 30-40% of the patients, respectively. In visualization of the ScA, UHR-CTA was better than C-CTA (P < 0.05, Fisher's exact test). Between the two observers, the Cohen's kappa coefficient was 0.77 for UHR-CTA and 0.78 for C-CTA. Conclusions: UHR-CTA is a simple and accessible method to evaluate intracranial vasculature. Visualization of the ScA with UHR-CTA was better than that with C-CTA. The high quality of UHR-CTA could provide useful information in the neurosurgery field.

  58. Basilar artery dissection with rupture 6 years after accidental detection: A case report. International-journal

    Yoshimichi Sato, Kuniyasu Niizuma, Hideki Ota, Hidenori Endo, Teiji Tominaga

    Surgical neurology international 12 4-4 2021

    DOI: 10.25259/SNI_735_2020  

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    Background: Chronic basilar artery dissection (BAD) is a rare pathology, and only a few reports have been mentioned in the literature. The imaging features of chronic BAD, especially those that develop into a subarachnoid hemorrhage (SAH), are unknown. Case Description: We report a unique case of a chronic BAD with a split intimal flap that developed into an SAH. A 74-year-old man was diagnosed with BAD. After considering all treatment options, conservative treatment was selected for the patient. We continued imaging follow-up of the patient in our outpatient clinic once a year. The BA gradually dilated and the internal flap split. The patient and his family refused surgical treatment; therefore, conservative treatment was continued. Six years and 2 months from the first diagnosis, he developed a massive SAH and died. Conclusion: In the case of this patient, the weakened condition of the internal elastic lamina may have caused dissection of the intimal flap between the intima and media. Furthermore, the dissection may have developed and connected the true lumen to the pseudolumen and induced BA rupture. Thereby, split of the internal flap could be a risk factor for rupture in chronic BAD.

  59. Association of intravenous administration of human Muse cells with deficit amelioration in a rat model of spinal cord injury. International-journal

    Takumi Kajitani, Toshiki Endo, Naoya Iwabuchi, Tomoo Inoue, Yoshiharu Takahashi, Takatsugu Abe, Kuniyasu Niizuma, Teiji Tominaga

    Journal of neurosurgery. Spine 34 (4) 1-8 2021/01/01

    DOI: 10.3171/2020.7.SPINE20293  

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    OBJECTIVE: Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury (SCI). METHODS: The authors used a rat model of thoracic spinal cord contusion injury. For Muse cell transplantation, the clinical product CL2020 containing 300,000 Muse cells was administered intravenously 1 day after midthoracic SCI. Animals were divided into CL2020 (n = 11) and vehicle-treated (n = 15) groups. Behavioral and histological evaluations were conducted over a period of 8 weeks to see whether intravenous CL2020 administration provided therapeutic effects for SCI. The effects of human-selective diphtheria toxin on reversion of the therapeutic effects of CL2020 were also investigated. RESULTS: Hindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, the cystic cavity formed after the injury was smaller in the CL2020 group. Furthermore, higher numbers of descending 5-hydroxytryptamine (5-HT) fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate most predominantly into neuronal cells in the injured spinal cord. CONCLUSIONS: Following SCI, Muse cells in CL2020 can reach the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fiber preservation and exerted therapeutic potential for severe SCI.

  60. マウスラクナ梗塞モデルに対するMuse細胞製品CL2020の治療効果の検討

    阿部 考貢, 油川 大輝, 新妻 邦泰, 串田 良祐, 若尾 昌平, 出澤 真理, 冨永 悌二

    脳循環代謝 32 (1) 99-99 2020/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  61. Vessel wall MRIによる脳動脈瘤の瘤壁造影効果 脳動脈瘤壁の質的診断

    遠藤 英徳, 面高 俊介, 新妻 邦泰, 藤村 幹, 佐藤 健一, 井上 敬, 江面 正幸, 上之原 広司, 冨永 悌二

    脳血管内治療 5 (Suppl.) 21-21 2020/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  62. もやもや病の最新研究・治療 成人もやもや病に対するバイパス術後の遅発性過灌流とRNF213遺伝子c.14576G>A多型の関連についての検討

    藤村 幹, 田代 亮介, 勝木 将人, 西澤 威人, 遠又 靖丈, 新妻 邦泰, 冨永 悌二

    脳循環代謝 32 (1) 70-70 2020/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  63. Prolonged/delayed cerebral hyperperfusion in adult patients with moyamoya disease with RNF213 gene polymorphism c.14576G>A (rs112735431) after superficial temporal artery-middle cerebral artery anastomosis. International-journal

    Ryosuke Tashiro, Miki Fujimura, Masahito Katsuki, Taketo Nishizawa, Yasutake Tomata, Kuniyasu Niizuma, Teiji Tominaga

    Journal of neurosurgery 1-8 2020/10/23

    DOI: 10.3171/2020.6.JNS201037  

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    OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for moyamoya disease (MMD), whereas cerebral hyperperfusion (CHP) is one of the potential complications of this procedure that can result in delayed intracerebral hemorrhage and/or neurological deterioration. Recent advances in perioperative management in the early postoperative period have significantly reduced the risk of CHP syndrome, but delayed intracerebral hemorrhage and prolonged/delayed CHP are still major clinical issues. The clinical implication of RNF213 gene polymorphism c.14576G>A (rs112735431), a susceptibility variant for MMD, includes early disease onset and a more severe form of MMD, but its significance in perioperative pathology is unknown. Thus, the authors investigated the role of RNF213 polymorphism in perioperative hemodynamics after STA-MCA anastomosis for MMD. METHODS: Among 96 consecutive adult patients with MMD comprising 105 hemispheres who underwent serial quantitative cerebral blood flow (CBF) analysis by N-isopropyl-p-[123I]iodoamphetamine SPECT after STA-MCA anastomosis, 66 patients consented to genetic analysis of RNF213. Patients were routinely maintained under strict blood pressure control during and after surgery. The local CBF values were quantified at the vascular territory supplied by the bypass on postoperative days (PODs) 1 and 7. The authors defined the radiological CHP phenomenon as a local CBF increase of more than 150% compared with the preoperative values, and then they investigated the correlation between RNF213 polymorphism and the development of CHP. RESULTS: CHP at POD 1 was observed in 23 hemispheres (23/73 hemispheres [31.5%]), and its incidence was not statistically different between groups (15/41 [36.6%] in RNF213-mutant group vs 8/32 [25.0%] in RNF213-wild type (WT) group; p = 0.321). CHP on POD 7, which is a relatively late period of the CHP phenomenon in MMD, was evident in 9 patients (9/73 hemispheres [12.3%]) after STA-MCA anastomosis. This prolonged/delayed CHP was exclusively observed in the RNF213-mutant group (9/41 [22.0%] in the RNF213-mutant group vs 0/32 [0.0%] in the RNF213-WT group; p = 0.004). Multivariate analysis revealed that RNF213 polymorphism was significantly associated with CBF increase on POD 7 (OR 5.47, 95% CI 1.06-28.35; p = 0.043). CONCLUSIONS: Prolonged/delayed CHP after revascularization surgery was exclusively found in the RNF213-mutant group. Although the exact mechanism underlying the contribution of RNF213 polymorphism to the prolonged/delayed CBF increase in patients with MMD is unclear, the current study suggests that genetic analysis of RNF213 is useful for predicting the perioperative pathology of patients with MMD.

  64. 超選択的Wada testによるオーダーメイド的局所脳機能評価

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 上利 大, 新妻 邦泰, 神 一敬, 浅黄 優, 中里 信和, 冨永 悌二

    臨床神経生理学 48 (5) 363-363 2020/10

    Publisher: (一社)日本臨床神経生理学会

    ISSN:1345-7101

    eISSN:2188-031X

  65. Physiologic blood flow is turbulent. International-journal Peer-reviewed

    Khalid M Saqr, Simon Tupin, Sherif Rashad, Toshiki Endo, Kuniyasu Niizuma, Teiji Tominaga, Makoto Ohta

    Scientific reports 10 (1) 15492-15492 2020/09/23

    DOI: 10.1038/s41598-020-72309-8  

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    Contemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier-Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley's exact solution of the Navier-Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic-biologic links that govern physiologic and pathologic processes.

  66. Cell-Based Therapy for Stroke: Musing With Muse Cells. International-journal Peer-reviewed

    You Jeong Park, Kuniyasu Niizuma, Maxim Mokin, Mari Dezawa, Cesar V Borlongan

    Stroke 51 (9) 2854-2862 2020/09

    DOI: 10.1161/STROKEAHA.120.030618  

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    Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host's inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells' unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

  67. Intractable Hiccups as the Primary Symptom of a Perimedullary Arteriovenous Fistula at the Craniocervical Junction. International-journal Peer-reviewed

    Keisuke Sasaki, Tomoo Inoue, Takashi Inoue, Yasuo Nishijima, Toshiki Endo, Masayuki Ezura, Hiroshi Uenohara, Kuniyasu Niizuma, Teiji Tominaga

    World neurosurgery 141 64-68 2020/09

    DOI: 10.1016/j.wneu.2020.06.013  

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    BACKGROUND: Hiccups are a well-known short-term phenomenon in daily life. If they persist or become intractable, they may be a primary symptom of a disease. Recent studies identified the medulla oblongata as the neuroanatomic center of the hiccup reflex arc. In previous cases, an isolated lesion at the dorsal side of the medulla oblongata induced intractable hiccups. CASE DESCRIPTION: We herein describe a patient with a perimedullary arteriovenous fistula (PMAVF) at the craniocervical junction who had intractable hiccups. A 70-year-old male presented with a 3-year history of intractable hiccups that continued for a few days every week. An initial examination failed to identify the underlying cause, and neither medicine nor self-treatment attenuated his symptoms. Intracranial T2-weighted magnetic resonance imaging showed a hyperintensity area within the dorsolateral medulla and flow voids along the dorsal side of the cervical spine. Angiography revealed PMAVF fed by the left C1 radiculomedullary artery. Obliteration of the fistula was performed, after which intractable hiccups had completely disappeared within 1 week. CONCLUSIONS: This is the first case report of PMAVF at the craniocervical junction presenting with intractable hiccups that suggested a lesion in the dorsal side of the medulla. The mechanisms underlying hiccups are also discussed.

  68. Direct Inspection with Dual Endoscope Technique via Bilateral Transforaminal Approach Leading to Complete Resection of Recurrent Colloid Cyst of the Third Ventricle. International-journal Peer-reviewed

    Atsushi Nakayashiki, Tomohiro Kawaguchi, Kuniyasu Niizuma, Mika Watanabe, Miki Fujimura, Teiji Tominaga

    World neurosurgery 141 272-277 2020/09

    DOI: 10.1016/j.wneu.2020.06.060  

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    BACKGROUND: Although endoscopic approaches are widely used for resection of colloid cysts because of the lower invasiveness, removal of the recurrent colloid cyst is still challenging. Total removal is sometimes difficult to achieve with single-port endoscopy because of the restricted access and working space. To compensate for these limitations, the dual endoscope technique via the bilateral transforaminal approach was chosen. CASE DESCRIPTION: A 34-year-old woman with recurrent colloid cyst of the third ventricle was admitted to our department. She had a history of endoscopic subtotal removal at another institution. Reoperation was scheduled and the endoscopic bilateral transforaminal approach was chosen to ensure total removal with minimum complication risk. After decompression, the cyst was retracted toward the third ventricle floor via the right foramen of Monro. Under direct inspection with an angled scope via the right foramen of Monro, the cyst attachment on the third ventricle roof was sharply dissected via the left foramen of Monro, resulting in total removal. CONCLUSIONS: The dual endoscope technique via the bilateral transforaminal approach can achieve better surgical outcome by obtaining direct visualization of the cyst attachment. Although the indication should be limited, this approach can be considered especially for patients with recurrent lesions involving possible adhesion to vital structures.

  69. The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. International-journal Peer-reviewed

    Sherif Rashad, Xiaobo Han, Kanako Sato, Eikan Mishima, Takaaki Abe, Teiji Tominaga, Kuniyasu Niizuma

    RNA biology 17 (8) 1092-1103 2020/08

    DOI: 10.1080/15476286.2020.1779492  

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    tiRNAs are small non-coding RNAs produced when tRNA is cleaved under stress. tRNA methylation modifications has emerged in recent years as important regulators for tRNA structural stability and sensitivity to cleavage and tiRNA generation during stress, however, the specificity and higher regulation of such a process is not fully understood. Alkbh1 is a m1A demethylase that leads to destabilization of tRNA and enhanced tRNA cleavage. We examined the impact of Alkbh1 targeting via gene knockdown or overexpression on B35 rat neuroblastoma cell line fate following stresses and on tRNA cleavage. We show that Alkbh1 impact on cell fate and tRNA cleavage is a stress specific process that is impacted by the demethylating capacity of the cellular stress in question. We also show that not all tRNAs are cleaved equally following Alkbh1 manipulation and stress, and that Alkbh1 KD fails to rescue tRNAs from cleavage following demethylating stresses. These findings shed a light on the specificity and higher regulation of tRNA cleavage and should act as a guide for future work exploring the utility of Alkbh1 as a therapeutic target for cancers or ischaemic insult.

  70. Preliminary Study of Eye-Tracking During the Coil Insertion Task in a Silastic Model of Intracranial Aneurysms. International-journal Peer-reviewed

    Masaaki Shojima, Yoshihiro Okamoto, Makoto Ohta, Kuniyasu Niizuma, Nobuyuki Sakai, Teiji Tominaga

    World neurosurgery 139 e827-e835 2020/07

    DOI: 10.1016/j.wneu.2020.05.012  

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    OBJECTIVE: Surgical skills are generally acquired by watching the "hand movements" of experts. "Eye movements" are now attracting attention in skill-learning fields. Eye-tracking technology was introduced preliminarily to develop a better skill-learning system for neuroendovascular treatments. METHODS: During a task to place a detachable coil into a silastic cerebral aneurysm model under biplane X-ray fluoroscopy, gaze points were recorded using a head-mount eye-tracking device. RESULTS: During the task, 91% of fixations were allocated to the monitor displaying fluoroscopic images, and the others to the hands of operators or unspecified visual targets. More than 80% of fixations were located in frontal or lateral fluoroscopic images. Fixations were placed more frequently around the aneurysm than the microcatheter. One operator failed to recognize the timing when the proximal marker of the coil overlapped that of the microcatheter. The subject allocated most fixations to the frontal fluoroscopic image, whereas other subjects placed most fixations to the lateral fluoroscopic image. Furthermore, that operator put no fixations to the proximal marker of the microcatheter. CONCLUSIONS: The results of this preliminary study imply the feasibility of the eye tracking-based learning system for neuroendovascular treatments. The eye-tracking analysis has potential in investigating or preventing procedural failures in neuroendovascular treatments.

  71. Stress Induced tRNA Halves (tiRNAs) as Biomarkers for Stroke and Stroke Therapy; Pre-clinical Study. International-journal Peer-reviewed

    Kanako Sato, Sherif Rashad, Kuniyasu Niizuma, Teiji Tominaga

    Neuroscience 434 44-54 2020/05/10

    DOI: 10.1016/j.neuroscience.2020.03.018  

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    tiRNAs are small non-coding RNAs generated by angiogenin-mediated tRNA cleavage during cellular stress. Some tiRNAs were shown to be cytoprotective, while other reports indicate that the generation of tiRNAs is cytotoxic. We used rat model of focal cerebral ischemia-reperfusion (I/R) injury to study the generation and regulation of tiRNAs following in vivo I/R and the impact of neuroprotective therapy on their generation. tiRNAs were induced after I/R and Minocycline therapy reduced global tiRNA levels. Our results showed that tRNA cleavage is tRNA species specific, and neuroprotective treatment does not affect all tiRNA species. We also evaluated the temporal changes in several tRNA modifying enzymes and showed a correlation between their expression and tRNA cleavage. In conclusion, we show that tiRNAs can serve as biomarkers for stroke and stroke therapy, further adding them to the repertoire of tools that can be used to monitor and treat stroke.

  72. Symptomatic Cerebral Hyperperfusion After Cerebral Vasospasm Associated with Aneurysmal Subarachnoid Hemorrhage. International-journal Peer-reviewed

    Hiroyuki Sakata, Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    World neurosurgery 137 379-383 2020/05

    DOI: 10.1016/j.wneu.2020.02.092  

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    BACKGROUND: Cerebral hyperperfusion syndrome, which carries a potential risk of intracranial hemorrhage, is a rare and overlooked condition in the setting of subarachnoid hemorrhage (SAH). CASE DESCRIPTION: A 72-year-old female presenting with SAH underwent clipping of a ruptured aneurysm of the left middle cerebral artery. On post-SAH day 7, the patient exhibited motor aphasia due to cerebral vasospasm of the left middle cerebral artery. After recovery from symptomatic cerebral vasospasm, the patient became restless and suffered from right hemiparesis on post-SAH day 12. Initially, recurrence of cerebral vasospasm was suspected; however, cerebral blood flow measurement using single-photon emission computed tomography revealed apparently increased perfusion in the same territory of the left middle cerebral artery. Hypertensive therapy was not induced during the postoperative period. Her neurologic symptoms and signs of cerebral hyperperfusion gradually improved with intensive blood pressure lowering. CONCLUSIONS: This is the first report to describe postischemic cerebral hyperperfusion syndrome after symptomatic vasospasm detected using sequential single-photon emission computed tomography during the acute stage of SAH. Early diagnosis of this rare phenomenon is crucial given the necessity to lower blood pressure for preventing hemorrhagic complications, which is contrary to the usual management of patients with vasospasm.

  73. Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach. International-journal Peer-reviewed

    Sherif Rashad, Daisuke Saigusa, Takahiro Yamazaki, Yotaro Matsumoto, Yoshihisa Tomioka, Ritsumi Saito, Akira Uruno, Kuniyasu Niizuma, Masayuki Yamamoto, Teiji Tominaga

    Scientific reports 10 (1) 6507-6507 2020/04/16

    DOI: 10.1038/s41598-020-63483-w  

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    Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.

  74. Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. International-journal Peer-reviewed

    Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    Scientific reports 10 (1) 6217-6217 2020/04/07

    DOI: 10.1038/s41598-020-62862-7  

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    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  75. Ruptured Basilar Artery Dissection Diagnosed Using Magnetic Resonance Vessel Wall Imaging and Treated with Coil Embolization with Overlapping LVIS Stents: A Case Report. Peer-reviewed

    Shinya Sonobe, Masahiro Yoshida, Kuniyasu Niizuma, Teiji Tominaga

    NMC case report journal 7 (2) 75-79 2020/04

    DOI: 10.2176/nmccrj.cr.2019-0141  

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    The diagnosis and treatment of patients with ruptured basilar artery dissection (rBAD) are often difficult. We present a case of rBAD diagnosed with magnetic resonance vessel wall imaging (MR-VWI) and treated with coil embolization with overlapping low-profile visualized intraluminal support (LVIS) stents. The case is of a 49-year-old woman with subarachnoid hemorrhage. digital subtraction angiography (DSA) showed irregularity in an anterior wall of the middle portion of the basilar artery, indicating the presence of a false lumen. MR-VWI showed local enhancement in an arterial wall, which was consistent with the wall irregularity observed in DSA. Overlapping stents (two LVIS stents) was performed in the basilar artery and coils were placed in the false lumen. The false lumen was completely thrombosed, and anterograde blood flow of the basilar artery was preserved. Dual antiplatelet therapy was administered, and the patient underwent an uneventful postoperative course. DSA performed 6 months later showed a white-collar sign. MR-VWI has attracted attention as a useful modality for detecting a ruptured lesion in patients with subarachnoid hemorrhage. This is the first report, to the best of our knowledge, describing the practical use of MR-VWI for rBAD. MR-VWI is suggested to improve diagnostic accuracy for rBAD. There are no established treatments for rBAD; reconstructive endovascular treatments comprising stent placement and coil embolization of a false lumen are promising. The LVIS stent has a braided design and high metal coverage ratio and is considered to be reasonable for use in rBAD. Coil embolization of a false lumen with overlapping LVIS stents may be effective for rBAD.

  76. Optimal Timing of Extracranial-Intracranial Bypass with Microsurgical Trapping for Ruptured Blister Aneurysms of the Internal Carotid Artery. International-journal Peer-reviewed

    Hidenori Endo, Miki Fujimura, Hiroaki Shimizu, Toshiki Endo, Shunsuke Omodaka, Takashi Inoue, Kenichi Sato, Kuniyasu Niizuma, Teiji Tominaga

    World neurosurgery 136 e567-e577 2020/04

    DOI: 10.1016/j.wneu.2020.01.081  

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    OBJECTIVE: Ruptured blister aneurysms of the internal carotid artery are challenging to treat because of their difficult diagnosis and the fragility of the wall structure. Here, we sought to clarify the efficacy of extracranial-intracranial bypass followed by trapping (bypass/trapping) for ruptured blister aneurysms. METHODS: A retrospective study identified 45 patients with ruptured blister aneurysms between 1998 and 2017. Our principle was to attempt bypass/trapping as early as possible after diagnosis (early surgery). If early diagnosis was difficult, patients underwent elective surgery in the later stage when aneurysms were detected (elective surgery). Patient characteristics, radiologic findings, clinical course, and outcomes were analyzed. RESULTS: Forty-three patients were treated by bypass/trapping. Twenty-eight patients were classified as early surgery and 15 as elective surgery. Two patients experienced fatal rebleeding and did not undergo surgery. All 15 patients in the elective surgery group showed rebleeding and/or aneurysmal growth while awaiting surgery. In the elective surgery group, 10 aneurysms were missed initially by catheter angiography. In the early surgery group, 9 patients were assessed by vessel wall magnetic resonance imaging, which showed circumferential enhancement along the aneurysm wall, most of which was shown as only a small bulge in the angiography. Postoperative rebleeding did not occur in any of the patients. CONCLUSIONS: Bypass/trapping is effective to prevent rebleeding. Early surgery may be beneficial, because most patients in the elective surgery group showed rebleeding or aneurysmal growth. Vessel wall magnetic resonance imaging is a useful adjunct for early diagnosis and may contribute to prompt early surgery.

  77. Case reports of latent HBV hepatitis in patients after neurosurgical treatment for hypothalamic and pituitary tumors. International-journal Peer-reviewed

    Kuniyasu Niizuma, Yoshikazu Ogawa, Takayuki Kogure, Teiji Tominaga

    BMC infectious diseases 20 (1) 230-230 2020/03/18

    DOI: 10.1186/s12879-020-04971-2  

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    BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION: This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION: Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.

  78. The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. International-journal Peer-reviewed

    Sherif Rashad, Khalid M Saqr, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    Scientific reports 10 (1) 3700-3700 2020/02/28

    DOI: 10.1038/s41598-020-60683-2  

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    Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.

  79. Octacalcium phosphate collagen composite (OCP/Col) enhance bone regeneration in a rat model of skull defect with dural defect. International-journal Peer-reviewed

    Takashi Sasaki, Kuniyasu Niizuma, Atsushi Kanoke, Keiko Matsui, Shogo Ogita, Sherif Rashad, Tadashi Kawai, Mika Watanabe, Hidenori Endo, Tetsu Takahashi, Shinji Kamakura, Teiji Tominaga

    Heliyon 6 (2) e03347 2020/02

    DOI: 10.1016/j.heliyon.2020.e03347  

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    Cranial bone defects are a major issue in the field of neurosurgery, and improper management of such defects can cause cosmetic issues as well as more serious infections and inflammation. Several strategies exist to manage these defects clinically, but most rely on synthetic materials that are prone to complications; thus, a bone regenerative approach would be superior. We tested a material (octacalcium phosphate collagen composite [OCP/Col]) that is known to enhance bone regeneration in a skull defect model in rats. Using a critical-sized rat skull defect model, OCP/Col was implanted in rats with an intact dura or with a partial defect of the dura. The results were compared with those in a no-treatment group over the course of 12 weeks using computed tomographic and histological analysis. OCP/Col enhanced bone regeneration, regardless of whether there was a defect of the dura. OCP/Col can be used to treat skull defects, even when the dura is injured or removed surgically, via bone regeneration with enhanced resorption of OCP/Col, thus limiting the risk of infection greatly.

  80. Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model. International-journal Peer-reviewed

    Takatsugu Abe, Daiki Aburakawa, Kuniyasu Niizuma, Naoya Iwabuchi, Takumi Kajitani, Shohei Wakao, Yoshihiro Kushida, Mari Dezawa, Cesar V Borlongan, Teiji Tominaga

    Stroke 51 (2) 601-611 2020/02

    DOI: 10.1161/STROKEAHA.119.026589  

    ISSN:0039-2499

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    Background and Purpose- Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell-based product CL2020 remain unanswered. Methods- Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5×104 cells/body; medium dose=1×104 cells/body; low dose=5×103 cells/body) at subacute phase (≈9 days after onset) and chronic phase (≈30 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed. Results- Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase-treated and chronic-phase-treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase-treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity. Conclusions- Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.

  81. Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs. International-journal Peer-reviewed

    Sherif Rashad, Xiaobo Han, Khalid Saqr, Simon Tupin, Makoto Ohta, Kuniyasu Niizuma, Teiji Tominaga

    Journal of cellular physiology 235 (11) 7827-7839 2020/01/08

    DOI: 10.1002/jcp.29436  

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    Endothelial cells (ECs) respond to flow stress via a variety of mechanisms, leading to various intracellular responses that can modulate the vessel wall and lead to diseases if the flow is disturbed. Mechano-microRNAs (miRNAs) are a subset of miRNAs in the ECs that are flow responsive. Mechano-miRNAs were shown to be related to atherosclerosis pathophysiology, and a number of them were identified as pathologic. Here, we exposed human carotid ECs to different wall shear stresses (WSS), high and low, and evaluated the response of miRNAs by microarray and quantitative polymerase chain reaction analysis. We discovered five new mechano-miRNAs that were not reported in that context previously to the best of our knowledge. Moreover, functional pathway analysis revealed that under low WSS conditions, several pathways regulating apoptosis are affected. In addition, KLF2 and KLF4, known atheroprotective genes, were downregulated under low WSS and upregulated under high WSS. KLF2 and VCAM1, both angiogenic, were upregulated under high WSS. NOS3, which is vascular protective, was also upregulated with higher WSS. On the contrary, ICAM-1 and E-selectin, both atherogenic and proinflammatory, were upregulated with high WSS. Collectively, the epigenetic landscape with the gene expression analysis reveals that low WSS is associated with a proapoptotic state, while high WSS is associated with a proliferative and proinflammatory state.

  82. XGBoost, a Machine Learning Method, Predicts Neurological Recovery in Patients with Cervical Spinal Cord Injury Peer-reviewed

    Tomoo Inoue, Daisuke Ichikawa, Taro Ueno, Maxwell Cheong, Takashi Inoue, William D. Whetstone, Toshiki Endo, Kuniyasu Nizuma, Teiji Tominaga

    Neurotrauma Reports 1 (1) 8-16 2020/01/01

    Publisher: Mary Ann Liebert Inc

    DOI: 10.1089/neur.2020.0009  

    eISSN:2689-288X

  83. Preliminary study of eye tracking to investigate the differences in gaze behaviors depending on the experience of neuroendovascular therapy. International-journal

    Masaaki Shojima, Yoshihiro Okamoto, Kuniyasu Niizuma, Makoto Ohta, Osamu Ishikawa, Ayano Fujisawa, Hiroyuki Tsukihara, Nobuyuki Sakai, Teiji Tominaga

    Surgical neurology international 11 351-351 2020

    DOI: 10.25259/SNI_543_2020  

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    Background: Neuroendovascular therapy is now the choice for the management of many neurovascular pathologies, and physicians with endovascular skills are in high demand. In addition to the traditional method of practicing hand movements to learn skills, a new strategy of practicing eye movements to learn skills is also attracting attention. This preliminary study explored the differences in gaze behavior depending on experience with endovascular procedures to be facilitated in future skill training in neuroendovascular therapy. Methods: Four physicians with experience of 3-412 neuroendovascular procedures wore eye-tracking devices during coil embolization of swine cervical arteries. Gaze metrics with direct correlations to the expertise of endovascular procedures were explored. Results: Gaze metrics with a positive direct correlation to experience included the proportion of fixation durations (PFD) in the screen area and the native images. Those with a negative direct correlation included the PFD in the off-screen area and the roadmap images and the average fixation durations in the off-screen and coil areas. During the parent artery occlusion procedure with detachable coils, more experienced operators preferred to look at native images rather than roadmap images and that less experienced operators tended to look down at their hands more frequently. Conclusion: This preliminary study demonstrated the feasibility of eye tracking to identify the differences in gaze behavior depending on the experience of endovascular procedures and may guide future eye-tracking studies in neuroendovascular therapy.

  84. Prediction of Functional Outcome in Patients with Acute Stroke by Measuring tRNA Derivatives. International-journal

    Tomohisa Ishida, Takashi Inoue, Kuniyasu Niizuma, Natsumi Konno, Chitose Suzuki, Tomoo Inoue, Masayuki Ezura, Hiroshi Uenohara, Takaaki Abe, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland) 49 (6) 639-646 2020

    DOI: 10.1159/000511627  

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    BACKGROUND AND PURPOSE: Transfer RNA (tRNA) is a noncoding RNA that delivers amino acids to ribosomes for protein synthesis. tRNA is also involved in cell stress response programs. Oxidative stress induces direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine (m1A), we can detect tRNA derivatives such as conformationally changed tRNA, tRNA-derived fragments, and mononucleotide-free m1A. Based on these findings, tRNA derivatives may have potential as an early tissue damage marker. The purpose of this study was to investigate the plasma tRNA derivatives in stroke patients to clarify whether tRNA derivatives in the acute phase can detect early brain damage and then predict the functional outcome. METHODS: Patients (75 patients with ischemic and 66 with hemorrhagic stroke) and 22 healthy volunteers were prospectively enrolled for this study between November 2016 and February 2019. Plasma samples were collected within 24 h and at 1 day, 7 days, and 30 days from the onset. Plasma tRNA derivative concentrations were measured by ELISA kit using the anti-m1A antibody. RESULTS: The plasma tRNA derivative level on admission was significantly increased in both ischemic (mean ± standard error, 232.2 ± 33.1 ng/mL) and hemorrhagic stroke patients (212 ± 23.4 ng/mL) compared to the healthy volunteers (86.0 ± 7.9 ng/mL) (p = 0.00042 and p = 0.00018, respectively). The infarction size (r = 0.445, p = 0.00018) and hematoma volumes (r = 0.33, p = 0.0072) were also significantly correlated with tRNA derivatives. The concentrations of tRNA derivatives were associated with poor functional outcome (Modified Rankin Scale score 3-6 at 30 days from the onset) in patients with ischemic stroke at 7 days after onset (p = 0.020). CONCLUSIONS: Stress-induced tRNA derivatives can detect brain tissue damage, predicting functional outcome in patients with ischemic stroke.

  85. A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood Peer-reviewed

    Tetsuya Sato, Shohei Wakao, Yoshihiro Kushida, Kazuki Tatsumi, Masaaki Kitada, Takatsugu Abe, Kuniyasu Niizuma, Teiji Tominaga, Shigeki Kushimoto, Mari Dezawa

    Cell Transplantation 29 096368972092357-096368972092357 2020/01/01

    Publisher: SAGE Publications

    DOI: 10.1177/0963689720923574  

    ISSN:0963-6897

    eISSN:1555-3892

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    Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.

  86. Efficacy of intra-arterial indocyanine green angiography for the microsurgical treatment of dural arteriovenous fistula: A case report. International-journal Peer-reviewed

    Keisuke Sasaki, Hidenori Endo, Kuniyasu Niizuma, Yasuo Nishijima, Shinichiro Osawa, Miki Fujimura, Teiji Tominaga

    Surgical neurology international 11 46-46 2020

    DOI: 10.25259/SNI_588_2019  

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    Background: In this study, we report a case of dural arteriovenous fistula (dAVF) that was successfully treated using intra-arterial indocyanine green (IA-ICG) videoangiography during open surgery. Moreover, the findings of IA-ICG videoangiography were compared with those of intraoperative digital subtraction angiography (DSA). Case Description: A 72-year-old male patient with a history of hypertension, hyperlipidemia, and thrombocytosis presented with generalized seizure. DSA revealed Cognard Type III dAVF in the superior wall of the left transverse sinus, which was fed by a single artery (the left occipital artery [OA]) and drained into a single vein (the left temporal cortical vein), without drainage into a venous sinus. Since transarterial embolization was considered challenging due to the tortuosity of the left OA, surgical interruption of the shunt was performed by craniotomy. After excising the feeding artery, we were unable to observed dAVF on intraoperative DSA. However, IA-ICG videoangiography revealed the remaining shunt, which was fed by the collateral route from the feeding artery. The shunting point and draining vein were then surgically resected to eliminate the shunt. The shunt was not observed during the second IA-ICG videoangiography conducted after resection. Conclusion: ICG videoangiography is a better method compared with DSA in terms of visualizing fine vascular lesions. In contrast to the typical intravenous administration, selective IA-ICG can be repeatedly injected at a minimal dose. IA-ICG is a useful intraoperative tool that can be used to evaluate the elimination of the dAVF.

  87. tRNA cleavage: a new insight. International-journal Peer-reviewed

    Sherif Rashad, Kuniyasu Niizuma, Teiji Tominaga

    Neural regeneration research 15 (1) 47-52 2020/01

    DOI: 10.4103/1673-5374.264447  

    ISSN:1673-5374

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    Over the past decades, tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others, holding more than half of all modifications occurring in RNA molecules. Moreover, tRNA was discovered to be a source of various small noncoding RNA species, such as the stress induced angiogenin cleaved tRNA halves (tiRNA) or the miRNA like tRNA derived fragments. tRNA cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species, including mammals. Under cellular stress conditions, tRNA undergoes conformational changes and angiogenin cleaves it into 3' and 5' halves. 5'tiRNA halves were shown to repress protein translations. tRNA cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis, however some data hints to the opposite; that tiRNA are cytotoxic or at least related to apoptosis initiation. tRNA cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and mitochondria. In this review, we will highlight the biology of tRNA cleavage, show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.

  88. 時間で追う脳虚血の病態と治療:(1)急性期 脳卒中急性期バイオマーカーとしてのtRNA代謝産物の臨床的有用性

    石田 朋久, 井上 敬, 佐々木 慶介, 井上 智夫, 江面 正幸, 上之原 広司, 阿部 高明, 新妻 邦泰, 冨永 悌二

    脳循環代謝 31 (1) 57-57 2019/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  89. 超選択的Wada testによる血管解剖と機能解剖のハイブリッド評価 Peer-reviewed

    大沢 伸一郎, 鈴木 匡子, 新妻 邦泰, 浮城 一司, 柿沼 一雄, 上利 大, 神 一敬, 斎藤 竜太, 金森 政之, 中里 信和, 冨永 悌二

    脳血管内治療 4 (Suppl.) S383-S383 2019/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  90. A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction. International-journal Peer-reviewed

    Ahmed Mansour, Sherif Rashad, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    Journal of neurosurgery 1-13 2019/10/18

    DOI: 10.3171/2019.7.JNS19212  

    ISSN:0022-3085

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    OBJECTIVE: Cerebral hyperperfusion (CHP) is associated with considerable morbidity. Its pathophysiology involves disruption of the blood-brain barrier (BBB) with subsequent events such as vasogenic brain edema and ischemic and/or hemorrhagic complications. Researchers are trying to mimic the condition of CHP; however, a proper animal model is still lacking. In this paper the authors report a novel surgically induced CHP model that mimics the reported pathophysiology of clinical CHP including BBB breakdown, white matter (WM) injury, inflammation, and cognitive impairment. METHODS: Male Sprague-Dawley rats were subjected to unilateral common carotid artery (CCA) occlusion and contralateral CCA stenosis. Three days after the initial surgery, the stenosis of CCA was released to induce CHP. Cortical regional cerebral blood flow was measured using laser speckle flowmetry. BBB breakdown was assessed by Evans blue dye extravasation and matrix metalloproteinase-9 levels. WM injury was investigated with Luxol fast blue staining. Cognitive function was assessed using the Barnes circular maze. Other changes pertaining to inflammation were also assessed. Sham-operated animals were prepared and used as controls. RESULTS: Cerebral blood flow was significantly raised in the cerebral cortex after CHP induction. CHP induced BBB breakdown evident by Evans blue dye extravasation, and matrix metalloproteinase-9 was identified as a possible culprit. WM degeneration was evident in the corpus callosum and corpus striatum. Immunohistochemistry revealed macrophage activation and glial cell upregulation as an inflammatory response to CHP in the striatum and cerebral cortex. CHP also caused significant impairments in spatial learning and memory compared with the sham-operated animals. CONCLUSIONS: The authors report a novel CHP model in rats that represents the pathophysiology of CHP observed in various clinical scenarios. This model was produced without the use of pharmacological agents; therefore, it is ideal to study the pathology of CHP as well as to perform preclinical drug trials.

  91. てんかん外科に必要な術中マッピング 超選択的Wada testによるオーダーメイド的脳機能評価 Peer-reviewed

    大沢 伸一郎, 鈴木 匡子, 浮城 一司, 柿沼 一雄, 上利 大, 浅黄 優, 新妻 邦泰, 三木 俊, 神 一敬, 中里 信和, 冨永 悌二

    臨床神経生理学 47 (5) 358-358 2019/10

    Publisher: (一社)日本臨床神経生理学会

    ISSN:1345-7101

    eISSN:2188-031X

  92. Circumferential wall enhancement in evolving intracranial aneurysms on magnetic resonance vessel wall imaging. Peer-reviewed

    Omodaka S, Endo H, Niizuma K, Fujimura M, Inoue T, Endo T, Sato K, Sugiyama SI, Tominaga T

    Journal of neurosurgery 131 1262-1268 2019/10

    DOI: 10.3171/2018.5.JNS18322  

    ISSN:0022-3085

  93. Arterial blood pressure correlates with 90-day mortality in sepsis patients: a retrospective multicenter derivation and validation study using high-frequency continuous data. International-journal Peer-reviewed

    Naoya Kobayashi, Atsuhiro Nakagawa, Daisuke Kudo, Tsukasa Ishigaki, Haruya Ishizuka, Kohji Saito, Yutaka Ejima, Toshihiro Wagatsuma, Hiroaki Toyama, Tomohiro Kawaguchi, Kuniyasu Niizuma, Kokichi Ando, Kenji Kurotaki, Michio Kumagai, Shigeki Kushimoto, Teiji Tominaga, Masanori Yamauchi

    Blood pressure monitoring 24 (5) 225-233 2019/10

    DOI: 10.1097/MBP.0000000000000398  

    ISSN:1359-5237

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    OBJECTIVE: To identify the outcome of patients with sepsis using high-frequency blood pressure data. MATERIALS AND METHODS: This retrospective observational study was conducted at a university hospital ICU (derivation study) and at two urban hospitals (validation study) with data from adult sepsis patients who visited the centers during the same period. The area under the curve (AUC) of blood pressure falling below threshold was calculated. The predictive 90-day mortality (primary endpoint) area under threshold (AUT) and critical blood pressure were calculated as the maximum area under the curve of the receiver operating characteristic curve (AUCROC) and the threshold minus average AUT (derivation study), respectively. For the validation study, the derived 90-day mortality AUCROC (using critical blood pressure) was compared with Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and APACHE III. RESULTS: Derivation cohort (N = 137): the drop area from the mean blood pressure of 70 mmHg at 24-48 hours most accurately predicted 90-day mortality [critical blood pressure, 67.8 mmHg; AUCROC, 0.763; 95% confidence interval (CI), 0.653-0.890]. Validation cohort (N = 141): the 90-day mortality AUCROC (0.776) compared with the AUCROC for SOFA (0.711), SAPSII (0.771), APACHE II (0.745), and APACHE III (0.710) was not significantly different from the critical blood pressure 67.8 mmHg (P = 0.420). CONCLUSION: High-frequency arterial blood pressure data of the period and extent of blood pressure depression can be useful in predicting the clinical outcomes of patients with sepsis.

  94. 超選択的Wada testによるオーダーメイド的脳機能評価 Peer-reviewed

    大沢 伸一郎, 鈴木 匡子, 新妻 邦泰, 浮城 一司, 柿沼 一雄, 上利 大, 神 一敬, 中里 信和, 冨永 悌二

    てんかん研究 37 (2) 693-693 2019/09

    Publisher: (一社)日本てんかん学会

    ISSN:0912-0890

    eISSN:1347-5509

  95. Genetic analysis of ring finger protein 213 (RNF213) c.14576G>A polymorphism in patients with vertebral artery dissection: a comparative study with moyamoya disease. International-journal Peer-reviewed

    Ryosuke Tashiro, Miki Fujimura, Hiroyuki Sakata, Hidenori Endo, Yasutake Tomata, Mika Sato-Maeda, Kuniyasu Niizuma, Teiji Tominaga

    Neurological research 41 (9) 811-816 2019/09

    DOI: 10.1080/01616412.2019.1615726  

    ISSN:0161-6412

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    Background: Intracranial vertebral artery dissection (VAD) and moyamoya disease (MMD) are rare cerebrovascular diseases, both of which have an ethnic predominance in the East Asian population. Disruption of the internal elastic lamina and subsequent rupture of the medial layer result in intracranial VAD. MMD is a chronic occlusive cerebrovascular disease of unknown etiology, in which the medial layer and internal elastic lamina of the intracranial arteries are significantly compromised. Recent genetic studies found ring finger protein 213 (RNF213) to be an important susceptibility gene for MMD in East Asian patients, but the association between VAD and RNF213 has not been investigated. . Methods: We investigated polymorphism of the RNF213 gene (c.14576G>A) in genomic DNA of 24 patients with intracranial VAD in comparison with 58 patients with definitive MMD and 48 healthy controls. Results: Although RNF213 gene polymorphism (c.14576G>A) was evident in 69% of the MMD patients (40/58), none of the patients with intracranial VAD had this characteristic polymorphism (0/24, p < 0.001). The incidence of RNF213 c.14576G>A polymorphism was 4.2% in healthy controls (2/48). After adjustment by age and sex, the incidence of RNF213 c.14576G>A was significantly lower in intracranial VAD patients (p = 0.021) than that in MMD patients. Conclusions: In contrast to MMD patients, the prevalence of RNF213 c.14576G>A polymorphism was significantly lower in patients with intracranial VAD. The RNF213 gene polymorphism may preferentially affect the cerebrovascular lesion in the anterior circulation, which is originated from the primitive internal carotid arteries. The genetic background underlying intracranial VAD should be elucidated in future studies. Abbreviations: VAD: vertebral artery dissection; MMD: moyamoya disease; RNF213: ring finger protein 213; CAD: carotid artery dissection.

  96. Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases. International-journal Peer-reviewed

    Osada Y, Shibahara I, Nakagawa A, Sakata H, Niizuma K, Saito R, Kanamori M, Fujimura M, Suzuki S, Tominaga T

    British journal of neurosurgery 34 (6) 1-6 2019/09

    DOI: 10.1080/02688697.2019.1667482  

    ISSN:0268-8697

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    Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

  97. tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells. International-journal Peer-reviewed

    Alaa Elkordy, Sherif Rashad, Heba Shehabeldeen, Eikan Mishima, Kuniyasu Niizuma, Takaaki Abe, Teiji Tominaga

    Brain research 1714 8-17 2019/07/01

    DOI: 10.1016/j.brainres.2019.02.019  

    ISSN:0006-8993

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    The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA). To study tiRNA generation in an in vitro model of ischemic-reperfusion injury, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which detects 1-methyladenosine (m1A) modification of tRNA. We demonstrated that oxygen-glucose deprivation induced tRNA cleavage and tiRNA generation. Time course analysis showed a dramatic up-regulation of tiRNA generation by oxygen-glucose deprivation (OGD) which started a few minutes after reperfusion. Minocycline, a neuroprotective antibiotic, treatment protected PC12 cells against OGD-reperfusion cell damage resulting in a marked down-regulation of the generated tiRNA. Our findings show that cleavage of tRNA and tiRNA generation in rat neuronal PC12 cells occurs with reperfusion injury and the detection of tiRNA could be used as a potential cell damage marker and treatment effect indicator for this type of injury.

  98. What does computational fluid dynamics tell us about intracranial aneurysms? A meta-analysis and critical review. International-journal Peer-reviewed

    Khalid M Saqr, Sherif Rashad, Simon Tupin, Kuniyasu Niizuma, Tamer Hassan, Teiji Tominaga, Makoto Ohta

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 40 (5) 271678X19854640-1039 2019/06/18

    DOI: 10.1177/0271678X19854640  

    ISSN:0271-678X

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    Despite the plethora of published studies on intracranial aneurysms (IAs) hemodynamic using computational fluid dynamics (CFD), limited progress has been made towards understanding the complex physics and biology underlying IA pathophysiology. Guided by 1733 published papers, we review and discuss the contemporary IA hemodynamics paradigm established through two decades of IA CFD simulations. We have traced the historical origins of simplified CFD models which impede the progress of comprehending IA pathology. We also delve into the debate concerning the Newtonian fluid assumption used to represent blood flow computationally. We evidently demonstrate that the Newtonian assumption, used in almost 90% of studies, might be insufficient to describe IA hemodynamics. In addition, some fundamental properties of the Navier-Stokes equation are revisited in supplementary material to highlight some widely spread misconceptions regarding wall shear stress (WSS) and its derivatives. Conclusively, our study draws a roadmap for next-generation IA CFD models to help researchers investigate the pathophysiology of IAs.

  99. Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia. Peer-reviewed

    Faheem H, Mansour A, Elkordy A, Rashad S, Shebl M, Madi M, Elwy S, Niizuma K, Tominaga T

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 64 206-213 2019/04

    DOI: 10.1016/j.jocn.2019.04.012  

    ISSN:0967-5868

  100. Transsphenoidal Removal of Retroclival Chondroma with Pituitary Transposition Manifesting as Repeated Subarachnoid Hemorrhage: A Case Report. Peer-reviewed

    Ogawa Y, Niizuma K, Tominaga T

    Journal of neurological surgery. Part A, Central European neurosurgery 80 (3) 228-232 2019/02

    DOI: 10.1055/s-0038-1677452  

    ISSN:2193-6315

  101. Identification of HLA-DRB1*04:10 allele as risk allele for Japanese moyamoya disease and its association with autoimmune thyroid disease: A case-control study. International-journal Peer-reviewed

    Ryosuke Tashiro, Kuniyasu Niizuma, Seik-Soon Khor, Katsushi Tokunaga, Miki Fujimura, Hiroyuki Sakata, Hidenori Endo, Hidetoshi Inoko, Koetsu Ogasawara, Teiji Tominaga

    PloS one 14 (8) e0220858 2019

    DOI: 10.1371/journal.pone.0220858  

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    BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology. Growing evidence suggest its involvement of autoimmune and genetic mechanisms in the pathogenesis of MMD. This study aims to clarify the association between HLA allele and MMD. METHODS: Case-control study: the DNA of 136 MMD patients in Japan was extracted and the genotype of human leukocyte antigen (HLA) from this DNA was determined by super-high-resolution single-molecule sequence-based typing using next-generation sequencing. Next, the frequency of each HLA allele (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1) was compared with those in the Japanese control database. In addition, haplotype estimation was performed using the expectation maximization algorithm. RESULTS: The frequencies of the HLA-DRB1*04:10 allele (4.77% vs. 1.47% in the control group; P = 1.7 × 10-3; odds ratio [OR] = 3.35) and of the HLA-DRB1*04:10-HLA-DQB1*04:02 haplotype (haplotype frequency 4.41% vs. 1.35% in the control group; P = 2.0 × 10-3; OR = 3.37) significantly increased. The frequency of thyroid diseases, such as Graves' disease and Hashimoto thyroiditis, increased in HLA-DRB1*04:10-positive MMD patients compared with that in HLA-DRB1*04:10-negative MMD patients. CONCLUSIONS: HLA-DRB1*04:10 is a risk allele and HLA-DRB1*04:10-HLA-DQB1*04:02 a risk haplotype for MMD. In addition, HLA-DRB1*04:10 is associated with thyroid disease in MMD patients.

  102. Incidence and Risk Factors of the Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis for Adult Moyamoya Disease. International-journal Peer-reviewed

    Ryosuke Tashiro, Miki Fujimura, Masayuki Kameyama, Shunji Mugikura, Hidenori Endo, Yohei Takeuchi, Yasutake Tomata, Kuniyasu Niizuma, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland) 47 (3-4) 178-187 2019

    DOI: 10.1159/000500802  

    ISSN:1015-9770

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    OBJECTIVE: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical management for adult moyamoya disease (MMD) patients, but local cerebral hyperperfusion (CHP) and cerebral ischemia are potential complications of this procedure. Recent hemodynamic analysis of the acute stage after revascularization surgery for MMD revealed a more complex and unique pathophysiological condition, the so-called "watershed shift (WS) phenomenon," which is defined as a paradoxical decrease in the cerebral blood flow (CBF) at the adjacent cortex near the site of local CHP. The objective of this study was to clarify the exact incidence, clinical presentation, and risk factors of the WS phenomenon after direct revascularization surgery for adult MMD. PATIENTS AND METHODS: Among 74 patients with MMD undergoing STA-MCA anastomosis for 78 affected hemispheres, 60 adult patients comprising 64 hemispheres underwent serial quantitative CBF analysis by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography after revascularization surgery. The local CBF was quantitatively measured at the site of anastomosis and the adjacent cortex before surgery, as well as on 1 and 7 days after surgery. Then, we investigated the incidence, clinical presentation, and risk factors of the WS phenomenon. RESULTS: The WS phenomenon was evident in 7 patients (7/64 hemispheres; 10.9%) after STA-MCA anastomosis for adult MMD. None of the patients developed neurological deterioration due to the WS phenomenon, but 1 patient developed reversible ischemic change on diffusion-weighted imaging at the site of the WS phenomenon. Multivariate analysis revealed that a lower preoperative CBF value was significantly associated with the occurrence of the WS phenomenon (20.3 ± 7.70 mL/100 g/min in WS-positive group vs. 31.7 ± 8.81 mL/100 g/min in WS-negative group, p= 1.1 × 10-2). CONCLUSIONS: The incidence of the WS phenomenon was as high as 10.9% after STA-MCA anastomosis for adult MMD. The clinical outcome of the WS phenomenon is generally favorable, but there is a potential risk for perioperative cerebral infarction. Thus, we recommend routine CBF measurement in the acute stage after revascularization surgery for adult MMD to avoid surgical complications, such as local CHP and cerebral ischemia, caused by the WS phenomenon. Concomitant detection of the WS phenomenon with local CHP is clinically important because blood pressure reduction to counteract local CHP may have to be avoided in the presence of the WS phenomenon.

  103. Mechanical Thrombectomy for Acute Ischemic Stroke Arising from Thrombus of the Left Superior Pulmonary Vein Stump after Left Pneumonectomy: A Case Report. Peer-reviewed

    Sonobe S, Yoshida M, Niizuma K, Tominaga T

    NMC case report journal 6 (1) 17-20 2019/01

    DOI: 10.2176/nmccrj.cr.2018-0163  

  104. Significance of Quantitative Cerebral Blood Flow Measurement in the Acute Stage after Revascularization Surgery for Adult Moyamoya Disease: Implication for the Pathological Threshold of Local Cerebral Hyperperfusion. International-journal Peer-reviewed

    Masayuki Kameyama, Miki Fujimura, Ryosuke Tashiro, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Shunji Mugikura, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland) 48 (3-6) 217-225 2019

    DOI: 10.1159/000504835  

    ISSN:1015-9770

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    OBJECTIVE: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a standard surgical procedure for adult patients with moyamoya disease (MMD) and plays a role in preventing ischemic and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is a potential complication of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the exact threshold of the pathological increase in postoperative cerebral blood flow (CBF) is unclear. Thus, we analyzed local CBF in the acute stage after revascularization surgery for adult MMD to predict CHP syndrome under modern perioperative management. MATERIALS AND METHODS: Fifty-nine consecutive adult MMD patients, aged 17-66 years old (mean 43.1), underwent STA-MCA anastomosis with indirect pial synangiosis for 65 affected hemispheres. All patients were perioperatively managed by strict blood pressure control (systolic pressure of 110-130 mm Hg) to prevent CHP syndrome. Local CBF at the site of anastomosis was quantitatively measured using the autoradiographic method by N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. We defined CHP phenomenon as a local CBF increase over 150% compared to the preoperative value. Then, we investigated the correlation between local hemodynamic change and the development of CHP syndrome. RESULTS: After 65 surgeries, 5 patients developed CHP syndrome, including 2 patients with delayed intracerebral hemorrhage (3.0%), 1 with symptomatic subarachnoid hemorrhage (1.5%), and 2 with focal neurological deterioration without hemorrhage. The CBF increase ratio was significantly higher in patients with CHP syndrome (270.7%) than in patients without CHP syndrome (135.2%, p = 0.003). Based on receiver operating characteristic analysis, the cutoff value for the pathological postoperative CBF increase ratio was 184.5% for CHP syndrome (sensitivity = 83.3%, specificity =  94.2%, area under the curve [AUC] value  =  0.825) and 241.3% for hemorrhagic CHP syndrome (sensitivity =  75.0%, specificity =  97.2%, AUC value  =  0.742). CONCLUSION: Quantitative measurement of the local CBF value in the early postoperative period provides essential information to predict CHP syndrome after STA-MCA anastomosis in patients with adult MMD. The pathological threshold of hemorrhagic CHP syndrome was as high as 241.3% by the local CBF increase ratio, but 2 patients (3.0%) developed delayed intracerebral hemorrhage in this series that were managed following the intensive perioperative management protocol. Thus, we recommend routine CBF measurement in the acute stage after direct revascularization surgery for adult MMD and satisfactory blood pressure control to avoid the deleterious effects of CHP.

  105. Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels as a Biomarker of Acute Intracerebral Hemorrhage. Peer-reviewed

    Inoue T, Ishida T, Inoue T, Saito A, Ezura M, Uenohara H, Fujimura M, Sato K, Endo T, Omodaka S, Endo H, Niizuma K, Tominaga T

    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (2) 490-494 2018/11

    Publisher: Elsevier BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2018.10.027  

    ISSN:1052-3057

  106. ラット上矢静脈洞血栓症モデルにおける、脳血流変化の観察

    濱崎 亮, 新妻 邦泰, Rashad Sherif, 清水 宏明, 冨永 悌二

    脳循環代謝 30 (1) 114-114 2018/10

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  107. Cord Compression Caused by a Tangled and Warped Lumbar Catheter After Lumboperitoneal Shunt Placement. Peer-reviewed

    Sato K, Endo T, Sakata H, Inoue T, Niizuma K, Tominaga T

    Neurospine 2018/10

    DOI: 10.14245/ns.1836114.057  

    ISSN:2586-6583

  108. Quantitative Characterization of Carotid Plaque Components Using MR Apparent Diffusion Coefficients and Longitudinal Relaxation Rates at 3T: A Comparison With Histology. International-journal Peer-reviewed

    Ota H, Tamura H, Itabashi R, Yazawa Y, Nakamura Y, Hisamatsu K, Takamatsu M, Endo H, Niizuma K, Enomoto Y, Nagasaka T, Kajita K, Watanabe M, Yoshimura S, Yuan C

    Journal of magnetic resonance imaging : JMRI 48 (6) 1657-1667 2018/10

    DOI: 10.1002/jmri.26216  

    ISSN:1053-1807

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    BACKGROUND: There is limited evidence of parametric MR mapping to characterize carotid plaques associated with cerebral ischemic events. PURPOSE: To explore the apparent diffusion coefficients (ADCs) and longitudinal relaxation rates (R1 ) of carotid plaques, including areas of hemorrhage, lipid-rich/necrotic core (LR/NC) without hemorrhage, and fibrous tissue (Fbr) STUDY TYPE: Prospective. SUBJECTS: Twelve patients who underwent carotid endarterectomy. FIELD STRENGTH/SEQUENCE: R1 was measured using double angle Look-Locker acquisition on 3T systems. Single-shot spin-echo echo-planar imaging with fat suppression and outer-volume suppression (OVS-DWEPI) with b values of 10 and 500 s/mm2 was used for diffusion-weighted imaging. ASSESSMENT: A phantom study using diluted gadolinium solutions and polyvinyl alcohol solutions was used to validate the two protocols. Regions of interest (ROIs) were manually outlined on MR images for areas of LR/NC, hemorrhage, and Fbr based on histological cross-sections. Pixel-based R1 and ADC values in the ROIs were plotted for each component. The probability density function of the plots determined the optimum contours to separate the three components in the ADC-R1 plane. The LR/NC, hemorrhage, and Fbr regions were mapped on MR images based on the above results and compared to histological results. STATISTICAL TESTS: The R1 values of the phantom measurements were tested using Bland-Altman analysis. The accuracies of the MRI classification were calculated. RESULTS: R1 values <8 s-1 calculated using our method agreed with those calculated using an inversion-recovery fast-spin-echo sequence (error, ≤0.1 s-1 ). ADC values obtained using OVS-DWEPI were 4.1% higher than those obtained using standard echo-planar imaging. LR/NC (R1 , 0.4-1.2 s-1 ; ADC, 0-1.5 μm2 /ms), hemorrhage (R1  ≥ 1.5 s-1 ; ADC, 0.5-1.5 μm2 /ms), and Fbr (R1 , 0.2-0.8 s-1 ; ADC, 1.5-2.9 μm2 /ms) were separated on the plots. The accuracies of MRI classification were LR/NC, 0.86; hemorrhage, 0.79; and Fbr, 0.77. CONCLUSION: The combination of ADC and R1 values measured using our method enabled differentiation among LR/NC, hemorrhage, and Fbr. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1657-1667.

  109. A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rats. International-journal Peer-reviewed

    Ahmed Mansour, Kuniyasu Niizuma, Sherif Rashad, Akira Sumiyoshi, Rie Ryoke, Hidenori Endo, Toshiki Endo, Kenichi Sato, Ryuta Kawashima, Teiji Tominaga

    Journal of neurosurgery 131 (3) 892-902 2018/09/07

    DOI: 10.3171/2018.3.JNS172274  

    ISSN:0022-3085

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    OBJECTIVE: The cognitive deficits of vascular dementia and the vasoocclusive state of moyamoya disease have often been mimicked with bilateral stenosis/occlusion of the common carotid artery (CCA) or internal carotid artery. However, the cerebral blood flow (CBF) declines abruptly in these models after ligation of the CCA, which differs from "chronic" cerebral hypoperfusion. While some modified but time-consuming techniques have used staged occlusion of both CCAs, others used microcoils for CCA stenosis, producing an adverse effect on the arterial endothelium. Thus, the authors developed a new chronic cerebral hypoperfusion (CCH) model with cognitive impairment and a low mortality rate in rats. METHODS: Male Sprague-Dawley rats were subjected to unilateral CCA occlusion and contralateral induction of CCA stenosis (modified CCA occlusion [mCCAO]) or a sham operation. Cortical regional CBF (rCBF) was measured using laser speckle flowmetry. Cognitive function was assessed using a Barnes circular maze (BCM). MRI studies were performed 4 weeks after the operation to evaluate cervical and intracranial arteries and parenchymal injury. Behavioral and histological studies were performed at 4 and 8 weeks after surgery. RESULTS: The mCCAO group revealed a gradual CBF reduction with a low mortality rate (2.3%). White matter degeneration was evident in the corpus callosum and corpus striatum. Although the cellular density declined in the hippocampus, MRI revealed no cerebral infarctions after mCCAO. Immunohistochemistry revealed upregulated inflammatory cells and angiogenesis in the hippocampus and cerebral cortex. Results of the BCM assessment indicated significant impairment in spatial learning and memory in the mCCAO group. Although some resolution of white matter injury was observed at 8 weeks, the animals still had cognitive impairment. CONCLUSIONS: The mCCAO is a straightforward method of producing a CCH model in rats. It is associated with a low mortality rate and could potentially be used to investigate vascular disease, moyamoya disease, and CCH. This model was verified for an extended time point of 8 weeks after surgery.

  110. 選択的後大脳動脈Wada testによる海馬機能評価

    大沢 伸一郎, 岩崎 真樹, 鈴木 匡子, 新妻 邦泰, 松本 康史, 神 一敬, 中里 信和, 冨永 悌二

    てんかん研究 36 (2) 420-420 2018/09

    Publisher: (一社)日本てんかん学会

    ISSN:0912-0890

    eISSN:1347-5509

  111. Stress-induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells. International-journal Peer-reviewed

    Alaa Elkordy, Eikan Mishima, Kuniyasu Niizuma, Yasutoshi Akiyama, Miki Fujimura, Teiji Tominaga, Takaaki Abe

    Journal of neurochemistry 146 (5) 560-569 2018/09

    DOI: 10.1111/jnc.14321  

    ISSN:0022-3042

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    Transfer RNA (tRNA) plays a role in stress response programs involved in various pathological conditions including neurological diseases. Under cell stress conditions, intracellular tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived fragments or tRNA-derived stress-induced RNA (tiRNA). Generated tiRNA contributes to the cell stress response and has potential cell protective effects. However, tiRNA generation under stress conditions in neuronal cells has not been fully elucidated. To examine angiogenin-mediated tiRNA generation in neuronal cells, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which specifically and sensitively detects tiRNA. Oxidative stress induced by arsenite and hydrogen peroxide caused tRNA cleavage and tiRNA generation in PC12 cells. We also demonstrated that oxygen-glucose deprivation, which is an in vitro model of ischemic-reperfusion injury, induced tRNA cleavage and tiRNA generation. In these stress conditions, the amount of generated tiRNA was associated with the degree of morphological cell damage. Time course analysis indicated that generation of tiRNA was prior to severe cell damage and cell death. Angiogenin over-expression did not influence the amount of tiRNA in normal culture conditions; however, it significantly increased tiRNA generation induced by cell stress conditions. Our findings show that angiogenin-mediated tiRNA generation can be induced in neuronal cells by different cell stressors, including ischemia-reperfusion. Additionally, detection of tiRNA could be used as a potential cell damage marker in neuronal cells. Cover Image for this issue: doi: 10.1111/jnc.14191.

  112. Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge. International-journal Peer-reviewed

    Valen-Sendstad K, Bergersen AW, Shimogonya Y, Goubergrits L, Bruening J, Pallares J, Cito S, Piskin S, Pekkan K, Geers AJ, Larrabide I, Rapaka S, Mihalef V, Fu W, Qiao A, Jain K, Roller S, Mardal KA, Kamakoti R, Spirka T, Ashton N, Revell A, Aristokleous N, Houston JG, Tsuji M, Ishida F, Menon PG, Browne LD, Broderick S, Shojima M, Koizumi S, Barbour M, Aliseda A, Morales HG, Lefèvre T, Hodis S, Al-Smadi YM, Tran JS, Marsden AL, Vaippummadhom S, Einstein GA, Brown AG, Debus K, Niizuma K, Rashad S, Sugiyama SI, Owais Khan M, Updegrove AR, Shadden SC, Cornelissen BMW, Majoie CBLM, Berg P, Saalfield S, Kono K, Steinman DA

    Cardiovascular engineering and technology 9 (4) 544-564 2018/09

    DOI: 10.1007/s13239-018-00374-2  

    ISSN:1869-408X

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    PURPOSE: Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline. METHODS: 3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods, boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters. RESULTS: A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability. CONCLUSIONS: Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters.

  113. Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation. International-journal Peer-reviewed

    Berg P, Voß S, Saalfeld S, Janiga G, Bergersen AW, Valen-Sendstad K, Bruening J, Goubergrits L, Spuler A, Cancelliere NM, Steinman DA, Pereira VM, Chiu TL, Tsang ACO, Chung BJ, Cebral JR, Cito S, Pallarès J, Copelli G, Csippa B, Paál G, Fujimura S, Takao H, Hodis S, Hille G, Karmonik C, Elias S, Kellermann K, Khan MO, Marsden AL, Morales HG, Piskin S, Finol EA, Pravdivtseva M, Rajabzadeh-Oghaz H, Paliwal N, Meng H, Seshadhri S, Howard M, Shojima M, Sugiyama SI, Niizuma K, Sindeev S, Frolov S, Wagner T, Brawanski A, Qian Y, Wu YA, Carlson KD, Dragomir-Daescu D, Beuing O

    Cardiovascular engineering and technology 9 (4) 565-581 2018/09

    DOI: 10.1007/s13239-018-00376-0  

    ISSN:1869-408X

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    PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. RESULTS: Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

  114. Metabolomic Analysis of Mouse Brain after a Transient Middle Cerebral Artery Occlusion by Mass Spectrometry Imaging. Peer-reviewed

    Abe T, Niizuma K, Kanoke A, Saigusa D, Saito R, Uruno A, Fujimura M, Yamamoto M, Tominaga T

    Neurologia medico-chirurgica 58 (9) 384-392 2018/09

    DOI: 10.2176/nmc.oa.2018-0054  

    ISSN:0470-8105

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    We performed metabolomic analyses of mouse brain using a transient middle cerebral artery occlusion (tMCAO) model with Matrix Assisted Laser Desorption/Ionization (MALDI)-mass spectrometry imaging (MSI) to reveal metabolite changes after cerebral ischemia. We selected and analyzed three metabolites, namely creatine (Cr), phosphocreatine (P-Cr), and ceramides (Cer), because these metabolites contribute to cell life and death. Eight-week-old male C57BL/6J mice were subjected to tMCAO via the intraluminal blockade of the middle cerebral artery (MCA) and reperfusion 60 min after the induction of ischemia. Each mouse was randomly assigned to one of the three groups; the groups were defined by the survival period after reperfusion: control, 1 h, and 24 h. Corrected samples were analyzed using MALDI-MSI. Results of MSI analysis showed the presence of several ionized substances and revealed spatial changes in some metabolites identified as precise substances, including Cr, P-Cr, Cer d18:1/18:0, phosphatidylcholine, L-glutamine, and L-histidine. Cr, P-Cr, and Cer d18:1/18:0 were changed after tMCAO, and P-Cr and Cer d18:1/18:0 accumulated over time in ischemic cores and surrounding areas following ischemia onset. The upregulation of P-Cr and Cer d18:1/18:0 was detected 1 h after tMCAO when no changes were evident on hematoxylin and eosin staining and immunofluorescence assay. P-Cr and Cer d18:1/18:0 can serve as neuroprotective therapies because they are biomarker candidates for cerebral ischemia.

  115. [Surgical Planning for a Giant Pituitary Adenoma Based on Evaluation of the Fine Feeding System and Angioarchitecture:A Case Report]. Peer-reviewed

    Aburakawa D, Ogawa Y, Sato K, Niizuma K, Tominaga T

    No shinkei geka. Neurological surgery 46 (8) 691-697 2018/08

    DOI: 10.11477/mf.1436203795  

    ISSN:0301-2603

  116. Biphasic Development of Focal Cerebral Hyperperfusion After Revascularization Surgery for Adult Moyamoya Disease Associated With Autosomal Dominant Polycystic Kidney Disease. International-journal Peer-reviewed

    Tashiro R, Fujimura M, Endo H, Endo T, Niizuma K, Tominaga T

    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 (11) 3256-3260 2018/08

    DOI: 10.1016/j.jstrokecerebrovasdis.2018.07.024  

    ISSN:1052-3057

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    BACKGROUND: Cerebral hyperperfusion (CHP) syndrome is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), but its biphasic and delayed development is extremely rare. CASE REPORT: A 47-year-old woman with autosomal dominant kidney disease (ADPKD) presented with transient ischemic attacks due to MMD, and underwent left STA-MCA anastomosis. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (123IMP-SPECT) 1 day after surgery revealed asymptomatic CHP at the site of anastomosis. Strict blood pressure control and minocycline hydrochloride relieved CHP at postoperative day 7. However, 2 days later, the patient complained of sensory aphasia, and 123IMP-SPECT demonstrated significant focal CHP at the site of anastomosis accompanying high-intensity signal on magnetic resonance (MR) imaging of fluid attenuated inversion recovery (FLAIR) in her left temporal lobe near the site of anastomosis. We continued strict blood pressure control and additionally administered free radical scavenger (Edaravone) and antiepileptic agents, which gradually improved sensory aphasia. MR imaging and 123IMP-SPECT also confirmed the amelioration of the FLAIR-high lesion and focal CHP in her left temporal lobe. Two months later, the patient underwent right STA-MCA anastomosis without complications. CONCLUSIONS: Although the underlying mechanism is unknown, biphasic development of focal CHP after revascularization surgery in an MMD patient with ADPKD is unique. Due to the potential vulnerability of the systemic vessels in ADPKD, it is conceivable that intrinsic vascular wall fragility in MMD could be enhanced by ADPKD and have partly led to this rare complication.

  117. Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia Peer-reviewed

    Sherif Rashad, Kuniyasu Niizuma, Daisuke Saigusa, Xiaobo Han, Mika Sato-Maeda, Ritsumi Saito, Akira Uruno, Miki Fujimura, Shuntaro Ikawa, Masayuki Yamamoto, Teiji Tominaga

    Neuroscience 384 188-202 2018/08/01

    Publisher: Elsevier Ltd

    DOI: 10.1016/j.neuroscience.2018.05.015  

    ISSN:1873-7544 0306-4522

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    Sphingosine-1-phosphate (S1P) is a sphingolipid molecule produced by the action of sphingosine kinases (SphK) on sphingosine. It possesses various intracellular functions through its interactions with intracellular proteins or via its action on five G-protein-coupled cell membrane receptors. Following transient global cerebral ischemia (tGCI), only the CA1 subregion of the hippocampus undergoes apoptosis. In this study, we evaluated S1P levels and S1P-processing enzyme expression in different hippocampal areas following tGCI in rats. We found that S1P was upregulated earlier in CA3 than in CA1. This was associated with upregulation of SphK1 in both regions however, SphK2 was downregulated quickly in CA3. S1P lyase was also downregulated in CA3, but not in CA1. Spinster 2, the S1P exporter, was upregulated early in both regions, but was quickly downregulated in CA3. Together, these effects explain the variable levels of S1P in the CA1 and CA3 areas and indicate that S1P levels play a role in the preferential resistance of the CA3 subregion to tGCI-induced ischemia. FTY720 did not improve neuronal survival in the CA1 subregion, indicating that these effects were due to intracellular S1P accumulation. In conclusion, the findings suggest that intracellular S1P levels affect neuronal cell fate following tGCI.

  118. Paradoxical Association of Symptomatic Local Vasogenic Edema with Global Cerebral Hypoperfusion after Direct Revascularization Surgery for Adult Moyamoya Disease. International-journal Peer-reviewed

    Tashiro R, Fujimura M, Mugikura S, Niizuma K, Endo H, Endo T, Tominaga T

    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 (8) e172-e176 2018/08

    DOI: 10.1016/j.jstrokecerebrovasdis.2018.03.002  

    ISSN:1052-3057

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    BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard treatment for Moyamoya disease (MMD). Cerebral hyperperfusion syndrome is a potential complication of this procedure and can cause local vasogenic edema and/or delayed intracerebral hemorrhage. Cerebral hypoperfusion is a contradictory postoperative pathophysiological condition implicated in MMD, but its association with symptomatic local vasogenic edema has not been reported. CASE REPORT: A 31-year-old woman with MMD underwent left STA-MCA anastomosis 3 months after a minor completed stroke in bilateral hemispheres. Eight hours after the operation, the patient developed neurological deterioration of dysarthria and mono-paresis in her right hand. Magnetic resonance (MR) angiography showed apparently patent STA-MCA bypass, whereas MR imaging of fluid-attenuated inversion recovery demonstrated a local high-signal-intensity lesion at the vascular territory supplied by the bypass. The apparent diffusion coefficient value was significantly increased in this lesion, suggesting local vasogenic edema formation. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography revealed global hypoperfusion in the left hemisphere. The administration of a free-radical scavenger and antiepileptic agent gradually relieved her symptoms, and MR imaging 1 month after surgery confirmed the complete disappearance of local vasogenic edema. CONCLUSIONS: Vasogenic edema may be associated not only with cerebral hyperperfusion but also with hypoperfusion after STA-MCA anastomosis for MMD. Although the exact mechanism of this rare association is unknown, the intrinsic vulnerability of intracranial vascular wall structures and the increased vascular permeability in MMD may partly explain the paradoxical association of hypoperfusion and local vasogenic edema.

  119. Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis. Peer-reviewed

    Rashad S, Niizuma K, Sato-Maeda M, Fujimura M, Mansour A, Endo H, Ikawa S, Tominaga T

    Brain research 1699 54-68 2018/07

    DOI: 10.1016/j.brainres.2018.06.029  

    ISSN:0006-8993

  120. Mid-term prognosis of non-functioning pituitary adenomas with high proliferative potential: really an aggressive variant? Peer-reviewed

    Yoshikazu Ogawa, Hidefumi Jokura, Kuniyasu Niizuma, Teiji Tominaga

    Journal of Neuro-Oncology 137 (3) 543-549 2018/05/01

    Publisher: Springer New York LLC

    DOI: 10.1007/s11060-017-2740-1  

    ISSN:1573-7373 0167-594X

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    Pituitary adenomas with high proliferation rate and rapid growth are well known, but the clinical characteristics, prognosis, and treatment algorithm remain unclear. The clinical characteristics and mid-term prognosis of patients with non-functioning pituitary adenomas with high proliferative potential were retrospectively investigated. This study identified 53 patients with Ki-67 labeling index of &gt  3% among 845 patients with non-functioning pituitary adenoma (6.3%) initially treated by surgery. Prophylactic treatment was not applied for patients with residual tumor, but salvage treatment was performed if tumor progression was identified within the follow-up period. Twenty-two patients remained progression-free, whereas 31 patients suffered tumor progression. Comparison of gross total removal (n = 22) and non-total removal (n = 31) groups showed significantly longer progression-free period in the former group (P &lt 0.001). As salvage treatment gamma knife radiosurgery was applied for 11 patients resulting in 10 patients remaining progression-free and regrowth in 1 patient. Fractionated irradiation was applied for 10 patients, resulting in 2 patients remaining progression-free, deaths in 5 patients including 3 of transformation to pituitary carcinoma, dementia in 1 patient caused by frontal lobe dysfunction, and progression in 2 patients requiring additional surgery and gamma knife radiosurgery. Temozolomide was administered in 2 patients, resulting in deaths in both patients including 1 transformation to pituitary carcinoma. Total removal and gamma knife radiosurgery can result in good outcome. However, the prognosis is extremely poor for patients inadequate for gamma knife radiosurgery. Development of new salvage treatments is essential.

  121. Accelerating Cell Therapy for Stroke in Japan: Regulatory Framework and Guidelines on Development of Cell-Based Products. International-journal Peer-reviewed

    Kiyohiro Houkin, Hideo Shichinohe, Koji Abe, Teruyo Arato, Mari Dezawa, Osamu Honmou, Nobutaka Horie, Yasuo Katayama, Kohsuke Kudo, Satoshi Kuroda, Tomohiro Matsuyama, Ichiro Miyai, Izumi Nagata, Kuniyasu Niizuma, Ken Sakushima, Masanori Sasaki, Norihiro Sato, Kenji Sawanobori, Satoshi Suda, Akihiko Taguchi, Teiji Tominaga, Haruko Yamamoto, Toru Yamashita, Toshiki Yoshimine

    Stroke 49 (4) e145-e152-e152 2018/04

    DOI: 10.1161/STROKEAHA.117.019216  

    ISSN:0039-2499

  122. Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms Peer-reviewed

    Sherif Rashad, Shin-Ichiro Sugiyama, Kuniyasu Niizuma, Kenichi Sato, Hidenori Endo, Shunsuke Omodaka, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga

    Journal of Neurosurgery 128 (3) 723-730 2018/03/01

    Publisher: American Association of Neurological Surgeons

    DOI: 10.3171/2016.10.JNS161695  

    ISSN:1933-0693 0022-3085

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    OBJECTIVE: Risk factors for aneurysm rupture have been extensively studied, with several factors showing significant correlations with rupture status. Several studies have shown that aneurysm shape and hemodynamics change after rupture. In the present study the authors investigated a static factor, the bifurcation angle, which does not change after rupture, to understand its effect on aneurysm rupture risk and hemodynamics. METHODS: A hospital database was retrospectively reviewed to identify patients with cerebral aneurysms treated surgically or endovascularly in the period between 2008 and 2015. After acquiring 3D rotational angiographic data, 3D stereolithography models were created and computational fluid dynamic analysis was performed using commercially available software. Patient data (age and sex), morphometric factors (aneurysm volume and maximum height, aspect ratio, bifurcation angle, bottleneck ratio, and neck/parent artery ratio), and hemodynamic factors (inflow coefficient and wall shear stress) were statistically compared between ruptured and unruptured groups. RESULTS: Seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Univariate analysis showed aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with a ruptured status. Logistic regression analysis showed that aspect ratio and bifurcation angle were significant predictors of a ruptured status. Bifurcation angle was inversely correlated with inflow coefficient (p &lt 0.0005), which in turn correlated directly with mean (p = 0.028) and maximum (p = 0.014) wall shear stress (WSS) using Pearson's correlation coefficient, whereas aspect ratio was inversely correlated with mean (0.012) and minimum (p = 0.018) WSS. CONCLUSIONS: Bifurcation angle and aspect ratio are independent predictors for aneurysm rupture. Bifurcation angle, which does not change after rupture, is correlated with hemodynamic factors including inflow coefficient and WSS, as well as rupture status. Aneurysms with the hands-up bifurcation configuration are more prone to rupture than aneurysms with other bifurcation configurations.

  123. Clinical Characteristics of Lumbosacral Spinal Dural Arteriovenous Fistula (DAVF)–Comparison with Thoracic DAVF Peer-reviewed

    Toshiki Endo, Takumi Kajitani, Tomoo Inoue, Kenichi Sato, Kuniyasu Niizuma, Hidenori Endo, Yasushi Matsumoto, Teiji Tominaga

    World Neurosurgery 110 e383-e388 2018/02/01

    Publisher: Elsevier Inc.

    DOI: 10.1016/j.wneu.2017.11.002  

    ISSN:1878-8769 1878-8750

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    Objective: Spinal dural arteriovenous fistula (DAVF) occurs at any spinal level, but the clinical characteristics of lumbosacral DAVF have not been well documented. The purpose of this study was to evaluate clinical characteristics of lumbosacral DAVF and compare these features with those in thoracic DAVF. Methods: Twenty-five consecutive patients with 16 thoracic and 9 lumbosacral DAVFs were included (mean age, 63.9 years 20 men). All patients presented with progressive myelopathy. Preoperative and postoperative neurologic deficits were compared between thoracic and lumbosacral DAVF groups. Using magnetic resonance imaging, the extent of T2 high-intensity areas and signal flow voids were documented. Follow-up after surgical interventions ranged from 6 to 96 months (mean, 38.1 months). Results: Preoperatively, patients suffering lumbosacral DAVF tended to be more severely disabled compared with thoracic DAVF patients. Lumbosacral DAVF patients exhibited diminished patellar (P = 0.04) and Achilles tendon reflexes (P &lt 0.01), while most thoracic DAVF patients exhibited hyperreflexia. In magnetic resonance imaging, signal flow voids around the spinal cord were evident in only 4 of 9 lumbosacral DAVF patients (P = 0.012). Rather, a serpentine signal flow void of the filum terminale was a hallmark of lumbosacral DAVFs to distinguish them from thoracic DAVFs. In the lumbosacral DAVF group, postoperative improvements were significantly better in micturition function (P = 0.02). Conclusions: In lumbosacral DAVF, postoperative micturition function recovery was superior to thoracic DAVF. Intradural lumbar signal flow void is indicative of lumbosacral DAVF. For appropriate management, it is important to recognize these differences between lumbosacral and thoracic DAVF.

  124. Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya disease: Involvement of intrinsic immune reaction in its pathogenesis. International-journal Peer-reviewed

    Miki Fujimura, Taku Fujimura, Aya Kakizaki, Mika Sato-Maeda, Kuniyasu Niizuma, Yasutake Tomata, Setsuya Aiba, Teiji Tominaga

    Brain research 1679 39-44 2018/01/15

    DOI: 10.1016/j.brainres.2017.11.013  

    ISSN:0006-8993

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    Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, intrinsic immune reactions such as autoimmune response has been implicated in the pathogenesis of MMD. Recently, the RING finger protein 213 (RNF213) was found to be an important risk gene for MMD, and is predominantly expressed in blood cells and the spleen. Thus, we hypothesized that patients with MMD represent an intrinsic autoimmune status mediated by M2-polarized macrophages, which play an important role in tissue remodeling and angiogenesis. We compared the serum level of soluble (s)CD163, an activating marker for CD163+ M2-polarized macrophages that has been implicated in a variety of autoimmune disorders, between MMD patients and healthy controls. We also analyzed serum levels of CXCL5, an augmented cytokines that has been correlated with the severity of autoimmune diseases. As a result, the serum sCD163 levels of MMD patients (281,465 pg/ml) were significantly higher than those of healthy controls (174,842 pg/ml) (p = .004). The serum CXCL5 levels of MMD patients (679.02 pg/ml) were significantly higher than those of healthy controls (401.79 pg/ml) (p = .046). There were no differences in the serum sCD163 and CXCL5 levels between each genotype of the RNF213 polymorphism (wild-type or variant) among MMD patients. Although this is a pilot study and further validation with larger number of samples is necessary, our results indicate that patients with MMD may have increased autoimmune activity, and our results shed light on the pathogenesis of MMD via CD163+ M2-polarized macrophages.

  125. Efficacy and safety of REVIVE SE thrombectomy device for acute ischemic stroke: River Japan (reperfuse ischemic vessels with endovascular recanalization device in Japan) Peer-reviewed

    Nobuyuki Sakai, Shinzo Ota, Yasushi Matsumoto, Rei Kondo, Tetsu Satow, Michiya Kubo, Tomoyuki Tsumoto, Yukiko Enomoto, Taketo Kataoka, Hirotoshi Imamura, Kenichi Todo, Mikito Hayakawa, Hiroshi Yamagami, Kazunori Toyoda, Yasushi Ito, Kenji Sugiu, Yuji Matsumaru, Shinichi Yoshimura, Tomoyuki Kono, Taku Hoshi, Sho Murase, Hidemitsu Adachi, Shinsuke Sato, Yohei Mineharu, Mikiya Beppu, Kampei Shimizu, Teishiki Shibata, Katsunori Asai, Ryushi Kondo, Kenichi Sato, Ichiro Suzuki, Kuniyasu Niizuma, Morio Nagahata, Yuichiro Tsurusaki, So Tokunaga, RIVER JAPAN Investigators

    Neurologia Medico-Chirurgica 58 (4) 164-172 2018

    Publisher: Japan Neurosurgical Society

    DOI: 10.2176/nmc.oa.2017-0145  

    ISSN:1349-8029 0470-8105

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    REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≤2a. Secondary endpoints were clot migration/embolization recanalization without symptomatic intracranial hemorrhage (ICH) at 24 hsymptomatic ICH good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≤10) at day 90 device-or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years males 46.9% middle cerebral artery (MCA) occlusion 83.7% median NIHSS score 17). A post-procedure TICI score ≤2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9-85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4-76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device-or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS.

  126. Embolization of ruptured arteriovenous malformations in the cerebellopontine angle cistern Peer-reviewed

    Hidenori Endo, Shin-ichiro Osawa, Yasushi Matsumoto, Toshiki Endo, Kenichi Sato, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    Neurosurgical Review 41 (1) 173-182 2018/01/01

    Publisher: Springer Verlag

    DOI: 10.1007/s10143-017-0832-1  

    ISSN:1437-2320 0344-5607

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    Among brainstem arteriovenous malformations (AVMs), there exist small AVMs predominantly located in the cerebellopontine angle cistern (CPAC) with minimal extension into the pial surface of the brainstem. However, previous studies of CPAC AVMs did not particularly discuss the role of embolization in the treatment of these lesions. This study was conducted to clarify the effectiveness and validity of embolization in the treatment of CPAC AVMs. We retrospectively reviewed five patients with CPAC AVMs who underwent endovascular treatment. These patients were treated with embolization followed by open surgery or gamma knife (GK) radiosurgery. Radiological findings and clinical course for these patients were then assessed. All five patients presented with a hemorrhage. Angiography revealed that the main feeder contained a dilated pontine perforating artery in all cases. Embolization through the dilated pontine perforating artery effectively reduced shunt flow within the nidus or obliterated associated aneurysms. Magnetic resonance imaging showed infarction on the lateral pons in four patients, one of which developed transient mild dizziness and mild ataxia of the right side. Subsequent open surgery was performed in three patients, and GK radiosurgery was performed in two patients without complications. At the end of the follow-up period, all patients demonstrated favorable outcomes. Postoperative rebleeding did not occur in any of the patients. Disappearance of the AVM was confirmed in four patients, except in the one patient treated with GK. Although ischemic complications should be noted, embolization of CPAC AVMs may be an appropriate treatment option to reduce the risk of subsequent surgery or radiosurgery.

  127. Application of Muse Cell Therapy to Stroke. Peer-reviewed

    Niizuma K, Borlongan CV, Tominaga T

    Advances in experimental medicine and biology 1103 167-186 2018

    DOI: 10.1007/978-4-431-56847-6_9  

    ISSN:0065-2598

  128. Patient with Recurrent Anterior Cerebral Artery Dissecting Aneurysm After Stent-Assisted Coil Embolization Successfully Treated with A3-A3 Anastomosis Peer-reviewed

    Yoshiharu Takahashi, Hidenori Endo, Toshiki Endo, Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    World Neurosurgery 109 77-81 2018/01/01

    Publisher: Elsevier Inc.

    DOI: 10.1016/j.wneu.2017.09.128  

    ISSN:1878-8769 1878-8750

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    Background With recent advances in endovascular devices and techniques, the use of endovascular treatment has been reported for intracranial dissecting aneurysms. However, the efficacy of this endovascular approach for intracranial dissection is still unknown. We report the case of a patient with a recurrent anterior cerebral artery (ACA) dissecting aneurysm after endovascular treatment. Case Description A 67-year-old woman underwent stent-assisted coil embolization for a ruptured ACA dissecting aneurysm of the left A2 segment. Aneurysmal dilatation was completely occluded after embolization. However, follow-up angiography 40 days after treatment showed compaction of the coil mass and reenlargement of the aneurysm. Open surgery was performed, considering the risk of rebleeding from the recurrent dissecting aneurysm. A3-A3 anastomosis followed by trapping of the coiled aneurysm along with the stent was successfully performed through the interhemispheric approach. The postoperative course was uneventful, and angiography 6 months after surgery revealed disappearance of the aneurysm and patency of the A3-A3 anastomosis. Conclusions Stent-assisted coil embolization for an ACA dissecting aneurysm may not be curative, and the coiled aneurysm may recur within a short time period. Microsurgical bypass trapping can be considered as the alterative or salvage treatment because of curability. Revascularization surgery, such as A3-A3 anastomosis, should be performed before trapping to avoid ischemic complications.

  129. 新規過灌流ラットモデルにおける血液脳関門破綻機序に関しての検討

    古山 陽佑, 新妻 邦泰, Ahmed Mansor, 清水 宏明, 冨永 悌二

    脳循環代謝 29 (1) 175-175 2017/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  130. 神経アポトーシスにおけるS1Pシグナル伝達 虚血性細胞死に対する抵抗性と脆弱性への関連(S1P signaling in neuronal apoptosis: links to resistance and vulnerability to ischemic cell death)

    Rashad Sherif, 新妻 邦泰, 三枝 大輔, 韓 笑波, 前田 美香, 藤村 幹, 井川 俊太郎, 冨永 悌二

    脳循環代謝 29 (1) 215-215 2017/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  131. Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning Peer-reviewed

    Yoshikazu Ogawa, Kuniyasu Niizuma, Teiji Tominaga

    CLINICAL NEUROLOGY AND NEUROSURGERY 162 36-40 2017/11

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.clineuro.2017.09.005  

    ISSN:0303-8467

    eISSN:1872-6968

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    Objectives: Craniopharyngioma is a slow-growing tumor, but long-term tumor control with maintenance of quality of life is sometimes very difficult to achieve, and hypothalamic disturbance should be strictly avoided in the treatment. However, management of the pituitary gland and/or pituitary stalk varies among surgeons and institutions. Patients and methods: This retrospective review identified 44 patients, 24 males and 20 females with craniopharyngiomas who were initially treated by surgery through the extended transsphenoidal approach with pituitary stalk sectioning at a single institute. If the tumor bed involved the posterior lobe of the pituitary gland, pituitary stalk, anterior and/or mid portion of the third ventricle floor, these structures were removed en-bloc together with the tumor. The closest attention was paid to preserve fine arteries running along the surface of optic chiasm and the lateral walls of the third ventricle. Surgical outcome and changes in postoperative endocrinological status were investigated. Results: Gross total removal was achieved in 40 of 44 patients (91%), and all patients could discharge without autonomic and/or thermal disturbances. Tumor remnants were identified with tight adhesion to the perforating arteries in 2 cases, tight adhesion to mammillary bodies in 1, and optic chiasm in 1. Administration of antidiuretic hormone could be discontinued in 23 of 44 patients (52.3%) with improved diabetes insipidus (DI), although no patient could discontinue glucocorticoid administration. Preservation of thyroid function was achieved in another 23 of 44 patients (52.3%), and recovery from DI was correlated with preservation of thyroid function (p = 0.016). Conclusion: Pituitary dysfunction is partially reversible even with pituitary stalk sectioning. Regrowth of tumor in the anterior and/or mid portion of the third ventricle floor including pituitary stalk can possibly be prevented by aggressive tumor removal, and co-achievement of long-term tumor control with maintenance of quality of life could be possible to preserve the lateral wall of the third ventricle.

  132. Intra-operative hemorrhage due to hyperperfusion during direct revascularization surgery in an adult patient with moyamoya disease: a case report Peer-reviewed

    Hiroki Uchida, Hidenori Endo, Miki Fujimura, Toshiki Endo, Kuniyasu Niizuma, Teiji Tominaga

    NEUROSURGICAL REVIEW 40 (4) 679-684 2017/10

    Publisher: SPRINGER

    DOI: 10.1007/s10143-017-0868-2  

    ISSN:0344-5607

    eISSN:1437-2320

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    Hemorrhagic complication is one of the notable surgical complications of the revascularization surgery for moyamoya disease (MMD). Cerebral hyperperfusion (CHP) has been considered as the underlying cause of this complication. It mostly occurs several days after surgery, but the intra-operative hemorrhage immediately after bypass has not been reported previously. A 21-year-old woman presented right thalamic hemorrhage and was diagnosed as having MMD by cerebral angiography. In light of the location of the hemorrhage at the vascular territory of posterior circulation and the manifestation of transient ischemic attack during the follow-up period, she underwent revascularization surgery to prevent future ischemic attack and rebleeding. Superficial temporal artery (STA) was uneventfully anastomosed to the temporal M4 branch of the middle cerebral artery in an end-to-side manner. A few minutes after the completion of the anastomosis, hemorrhage occurred in the fissure adjacent to the site of anastomosis. Indocyanine green (ICG) video angiography just before hemorrhage showed focal early filling through the STA graft with early venous filling around the site of the anastomosis. The bleeding was controlled by immediate hypotensive therapy (systolic blood pressure 117 to 91 mmHg). The mean blood flows of the STA graft measured by ultrasonic flowmetry before and after hypotensive therapy were 52.8 and 24.2 ml/min, respectively. Single-photon emission computed tomography (SPECT) on the next day after surgery showed focal hyperperfusion in the surgical side. Intra-operative ultrasonic flowmetry, ICG, and postoperative SPECT would explain that CHP was the potential cause of the hemorrhagic complication. This is the first case describing intra-operative hemorrhagic complication during revascularization surgery for MMD. Surgeons need to be aware of this rare complication and its management method.

  133. Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex Peer-reviewed

    Mika Sato-Maeda, Miki Fujimura, Sherif Rashad, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Shuntaro Ikawa, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 (9) 1904-1911 2017/09

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.032  

    ISSN:1052-3057

    eISSN:1532-8511

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    The RING finger protein 213 (RNF213) is an important susceptibility gene for moyamoya disease (MMD) and is also implicated in other types of intracranial major artery stenosis/occlusion (ICAS); however, the role of RNF213 in the development of ICAS including MMD is unclear. The constitutive expression of the RNF213 gene is relatively weak in brain tissue, while information regarding the expression patterns of the RNF213 gene under cerebral ischemia, which is one of characteristic pathologies associated with ICAS, is currently limited. Our objective was to address this critical issue, and we investigated Rnf213 mRNA expression in rat brains after 5 minutes of transient global cerebral ischemia (tGCI) by occluding the common carotid arteries coupled with severe hypotension. Rnf213 gene expression patterns were investigated with in situ RNA hybridization and a real-time polymerase chain reaction (PCR) from 1 to 72 hours after tGCI. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the hippocampus CA1 sub-region 48 hours after tGCI. The significant induction of the Rnf213 gene was also evident in the ischemic cortex. Double staining of Rnf213 mRNA with NeuN immunohistochemistry revealed Rnf213 hybridization signal expression exclusively in neurons. The real-time PCR analysis confirmed the induction of the Rnf213 gene after tGCI. The up-regulation of the Rnf213 gene in vulnerable neurons in the hippocampus CA1 after tGCI suggests its involvement in forebrain ischemia, which is an underlying pathology of MMD. Further investigations are needed to elucidate its exact role in the pathophysiology of ICAS including MMD.

  134. Endovascular Treatment for carotid blowout syndrome after radiation for esophageal cancer: A case report Peer-reviewed

    Shigefumi Takahashi, Tomohiro Kawaguchi, Kuniyasu Niizuma, Atsuhiro Nakagawa, Miki Fujimura, Takenori Ogawa, Yukio Katori, Teiji Tominaga

    Neurological Surgery 45 (9) 791-798 2017/09/01

    Publisher: Igaku-Shoin Ltd

    DOI: 10.11477/mf.1436203594  

    ISSN:1882-1251 0301-2603

    eISSN:1882-1251

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    Here, we discuss a case of carotid blowout syndrome successfully treated with endovascular parent artery occlusion. A 71-year-old woman underwent treatment for esophageal cancer resection, followed by 50-Gy radiotherapy. 19 years prior. Due to local recurrence, she underwent 66- and 72-Gy radiation treatments at 2 and 4 years after the initial treatment, respectively. Afterward, tracheostomy and enterostomy were performed. This time, she was transported to our emergency department because of acute eruptive bleeding from the tracheal tube. As her vitals indicated shock, emergency endovascular treatment was performed. Digital subtraction angiography revealed that the common carotid artery in the left-sided of the neck had a pseudoaneurysm extruding to the pharyngeal cavity, which was considered to be the lesion responsible for the acute rupture. She was diagnosed as having carotid blowout syndrome. Balloon test occlusion showed that the cross flow via the anterior and posterior communicating arteries was sufficient, so parent artery occlusion was chosen for bleeding control. Carotid bifurcation was preserved to keep the collateral circulation via the external carotid artery. The patient was discharged 22 days after treatment, without any neurological deficits. Although injured vessel removal with high-flow bypass was an ideal treatment to achieve bleeding control without ischemic complication, endovascular treatment can be an efficient second-best treatment. To minimize the risk of late ischemic complications, flow preservation via carotid bifurcation might be important.

  135. Navigation-guided clipping of a de novo aneurysm associated with superficial temporal artery-middle cerebral artery bypass combined with indirect pial synangiosis in a patient with moyamoya disease Peer-reviewed

    Daiki Aburakawa, Miki Fujimura, Kuniyasu Niizuma, Hiroyuki Sakata, Hidenori Endo, Teiji Tominaga

    NEUROSURGICAL REVIEW 40 (3) 517-521 2017/07

    Publisher: SPRINGER

    DOI: 10.1007/s10143-017-0866-4  

    ISSN:0344-5607

    eISSN:1437-2320

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    De novo aneurysms associated with superficial temporal artery (STA)-middle cerebral artery (MCA) bypass are an extremely rare complication of direct revascularization surgery for moyamoya disease (MMD). The basic pathology of MMD includes fragility of the intracranial arterial wall characterized by medial layer thinness and waving of the internal elastic lamina. However, the incidence of newly formed aneurysms at the site of anastomosis currently remains unknown. Among 317 consecutive direct/indirect combined revascularization surgeries performed for MMD, we encountered a 52-year-old woman manifesting a de novo aneurysm adjacent to the site of anastomosis 11 years after successful STA-MCA bypass with encephalo-duro-myo-synangiosis (EDMS). Although the patient remained asymptomatic, the aneurysm gradually increased in diameter to more than 6 mm with the formation of a daughter sac, and a computational fluid dynamic study revealed low wall shear stress at the aneurysm dome. The patient underwent microsurgical clipping of the aneurysm using a neuro-navigation system that permitted the minimally invasive dissection of the temporal muscle flap used for EDMS at the site of the aneurysm without affecting pial synangiosis. The aneurysm was successfully occluded using a titanium clip without complications. The postoperative course was uneventful, and the patient was discharged without neurological deficits. De novo aneurysms associated with STA-MCA bypass for MMD may be safely treated with microsurgical clipping, even in cases initially managed by a combined revascularization procedure that includes complex pial synangiosis. We recommend the application of the neuro-navigation system for the maximum preservation of pial synangiosis during this procedure.

  136. Uneven cerebral hemodynamic change as a cause of neurological deterioration in the acute stage after direct revascularization for moyamoya disease: cerebral hyperperfusion and remote ischemia caused by the 'watershed shift' Peer-reviewed

    Xian-kun Tu, Miki Fujimura, Sherif Rashad, Shunji Mugikura, Hiroyuki Sakata, Kuniyasu Niizuma, Teiji Tominaga

    NEUROSURGICAL REVIEW 40 (3) 507-512 2017/07

    Publisher: SPRINGER

    DOI: 10.1007/s10143-017-0845-9  

    ISSN:0344-5607

    eISSN:1437-2320

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    Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is the standard surgical treatment for moyamoya disease (MMD). The main potential complications of this treatment are cerebral hyperperfusion (CHP) syndrome and ischemia, and their managements are contradictory to each other. We retrospectively investigated the incidence of the simultaneous manifestation of CHP and infarction after surgery for MMD. Of the 162 consecutive direct revascularization surgeries performed for MMD, we encountered two adult cases (1.2%) manifesting the simultaneous occurrence of symptomatic CHP and remote infarction in the acute stage. A 47-year-old man initially presenting with infarction developed CHP syndrome (aphasia) 2 days after left STA-MCA anastomosis, as assessed by quantitative single-photon emission computed tomography (SPECT). Although lowering blood pressure ameliorated his symptoms, he developed cerebral infarction at a remote area in the acute stage. Another 63-year-old man, who initially had progressing stroke, presented with aphasia due to focal CHP in the left temporal lobe associated with acute infarction at the tip of the left frontal lobe 1 day after left STA-MCA anastomosis, when SPECT showed a paradoxical decrease in cerebral blood flow (CBF) in the left frontal lobe despite a marked increase in CBF at the site of anastomosis. Symptoms were ameliorated in both patients with the normalization of CBF, and there were no further cerebrovascular events during the follow-up period. CHP and cerebral infarction may occur simultaneously not only due to blood pressure lowering against CHP, but also to the 'watershed shift' phenomenon, which needs to be elucidated in future studies.

  137. Circumferential Wall Enhancement on Magnetic Resonance Imaging is Useful to Identify Rupture Site in Patients with Multiple Cerebral Aneurysms Peer-reviewed

    Shunsuke Omodaka, Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Toshiki Endo, Kenichi Sato, Shin-ichiro Sugiyama, Takashi Inoue, Teiji Tominaga

    Neurosurgery 2017/06/06

    DOI: 10.1093/neuros/nyx267  

  138. Fine morphological evaluation of hypothalamus in patients with hyperphagia Peer-reviewed

    Yoshikazu Ogawa, Kuniyasu Niizuma, Teiji Tominaga

    ACTA NEUROCHIRURGICA 159 (5) 865-871 2017/05

    Publisher: SPRINGER WIEN

    DOI: 10.1007/s00701-017-3112-5  

    ISSN:0001-6268

    eISSN:0942-0940

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    Various metabolic diseases induced by eating disorders are some of the most serious and difficult problems for modern public healthcare. However, little is known about hyperphagia, partly because of the lack of a clear definition. Several basic studies have analyzed eating habits using endocrinological or neurophysiological approaches, which have suggested a controlled balance between the hunger and satiety centers in the central nervous system. However, more detailed neuro-radiologic evaluations have not been achieved for the hypothalamus, and evaluations were limited only to the floor of the third ventricles. Fine structures of hypothalamic morphology were investigated using high-resolution magnetic resonance imaging in seven patients with hypothalamo-pituitary tumors, who suffered from preoperative hyperphagia-induced severe obesity and metabolic disorders. Body mass index (BMI) varied from 22.4 to 40.5 kg/m(2) (mean 32.8 kg/m(2)). Clinical data were compared with the data of nine patients without hyperphagia and seven healthy volunteers. Morphological evaluation was possible in all patients and control subjects, and patients with hyperphagia had significantly shortened maximum distances between the ependymal layers of the lateral wall of the third ventricle and fornixes (hyperphagia group right side 0.30 mm, left side 0.23 mm vs. patients without hyperphagia group right side 1.60, left side 1.53 vs. healthy group right side 1.73 mm, left side 1.85 mm) (p &lt; 0.01). Two patients achieved postoperative improvement in both clinical and neuro-radiological findings. Eating and metabolic disorders are related to strong dysfunction of the medial nuclei of the hypothalamus in patients with hypothalamo-pituitary tumors. We report the first case of dynamic improvement from hyperphagia, with both symptomatic and neuro-radiological findings.

  139. Embolization of the choroidal artery in the treatment of cerebral arteriovenous malformations Peer-reviewed

    Alaa Elkordy, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Ryushi Kondo, Kuniyasu Niizuma, Toshiki Endo, Miki Fujimura, Teiji Tominaga

    JOURNAL OF NEUROSURGERY 126 (4) 1114-1122 2017/04

    Publisher: AMER ASSOC NEUROLOGICAL SURGEONS

    DOI: 10.3171/2016.2.JNS152370  

    ISSN:0022-3085

    eISSN:1933-0693

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    OBJECTIVE The anterior and posterior choroidal arteries are often recruited to supply arteriovenous malformations (AVMs) involving important paraventricular structures, such as the basal ganglia, internal capsule, optic radiation, lateral geniculate body, and medial temporal lobe. Endovascular embolization through these arteries is theoretically dangerous because they supply eloquent territories, are of small caliber, and lack collaterals. This study aimed to investigate the safety and efficacy of embolization through these arteries. METHODS This study retrospectively reviewed 13 patients with cerebral AVMs who underwent endovascular embolization through the choroidal arteries between 2006 and 2014. Embolization was performed as a palliative procedure before open surgery or Gamma Knife radiosurgery. Computed tomography and MRI were performed the day after embolization to assess any surgical complications. The incidence and type of complications and their association with clinical outcomes were analyzed. RESULTS Decreased blood flow was achieved in all patients after embolization. Postoperative CT detected no hemorrhagic complications. In contrast, postoperative MRI detected that 4 of the 13 patients (30.7%) developed infarctions: 3 patients after embolization through the anterior choroidal artery, and 1 patient after embolization through the lateral posterior choroidal artery. Two of the 4 patients in whom embolization was from the cisternal segment of the anterior choroidal artery (proximal to the plexal point) developed symptomatic infarction of the posterior limb of the internal capsule, 1 of whom developed morbidity (7.7%). The treatment-related mortality rate was 0%. Additional treatment was performed in 12 patients: open surgery in 9 and Gamma Knife radiosurgery in 3 patients. Complete obliteration was confirmed by angiography at the last follow-up in 10 patients. Recurrent bleeding from the AVMs did not occur in any of the cases during the follow-up period. CONCLUSIONS Ischemic complications are possible following the embolization of cerebral AVMs through the choroidal artery, even with modern neurointerventional devices and techniques. Although further study is needed, embolization through the choroidal artery may be an appropriate treatment option when the risk of surgery or radiosurgery is considered to outweigh the risk of embolization.

  140. Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model Peer-reviewed

    Hiroki Uchida, Kuniyasu Niizuma, Yoshihiro Kushida, Shohei Wakao, Teiji Tominaga, Cesario V. Borlongan, Mari Dezawa

    STROKE 48 (2) 428-435 2017/02

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1161/STROKEAHA.116.014950  

    ISSN:0039-2499

    eISSN:1524-4628

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    Background and Purpose Multilineage-differentiating stress-enduring (muse) cells are endogenous nontumorigenic stem cells with pluripotency harvestable as pluripotent marker SSEA-3(+) cells from the bone marrow from cultured bone marrow-mesenchymal stem cells. After transplantation into neurological disease models, muse cells exert repair effects, but the exact mechanism remains inconclusive. Methods We conducted mechanism-based experiments by transplanting serum/xeno-free cultured-human bone marrow-muse cells into the perilesion brain at 2 weeks after lacunar infarction in immunodeficient mice. Results Approximately 28% of initially transplanted muse cells remained in the host brain at 8 weeks, spontaneously differentiated into cells expressing NeuN (approximate to 62%), MAP2 (approximate to 30%), and GST-pi (approximate to 12%). Dextran tracing revealed connections between host neurons and muse cells at the lesioned motor cortex and the anterior horn. Muse cells extended neurites through the ipsilateral pyramidal tract, crossed to contralateral side, and reached to the pyramidal tract in the dorsal funiculus of spinal cord. Muse-transplanted stroke mice displayed significant recovery in cylinder tests, which was reverted by the human-selective diphtheria toxin. At 10 months post-transplantation, human-specific Alu sequence was detected only in the brain but not in other organs, with no evidence of tumor formation. Conclusions Transplantation at the delayed subacute phase showed muse cells differentiated into neural cells, facilitated neural reconstruction, improved functions, and displayed solid safety outcomes over prolonged graft maturation period, indicating their therapeutic potential for lacunar stroke.

  141. Efficacy of Revascularization Surgery for the Adult Patients with Hemorrhagic-onset Moyamoya Disease Peer-reviewed

    Miki Fujimura, Hidenori Endo, Kuniyasu Niizuma, Teiji Tominaga

    Japanese Journal of Neurosurgery 26 (2) 112-116 2017/02

    Publisher: The Japanese Congress of Neurological Surgeons

    DOI: 10.7887/jcns.26.112  

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    <p>  Moyamoya disease is a chronic cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Increasing evidence suggests that surgical revascularization such as direct extracranial-intracranial bypass has potential roles not only for preventing ischemic stroke, but also for reducing the risk of re-bleeding in adult patients with hemorrhagic-onset. Based on these observations, we performed direct/indirect combined revascularization surgery for eleven affected hemispheres of ten adult patients presenting with intracranial hemorrhage. The results of revascularization surgeries were favorable in all patients, and no patient suffered cerebrovascular event during the follow-up period.</p>

  142. Impact of bifurcation angle and inflow coefficient on rupture risk of bifurcation type basilar artery top aneurysms

    Rashad Sherif, Sugiyama Shin-ichiro, Niizuma Kuniyasu, Tominaga Teiji

    Transactions of Japanese Society for Medical and Biological Engineering 55 (5) 412-412 2017

    Publisher: Japanese Society for Medical and Biological Engineering

    DOI: 10.11239/jsmbe.55Annual.412  

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    <p>Risk factors for aneurysm rupture have been studied extensively in the past, with several factors showing significant correlations with rupture status. We analysed seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Patient data (age and sex), morphometric factors (aneurysm maximum height and volume, aspect ratio, bifurcation angle, bottleneck ratio, and neck-parent artery ratio) and hemodynamic factors (inflow coefficient and wall shear stress) were compared between ruptured and unruptured groups, and statistically analyzed. Aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with the rupture status on univariate analysis. Logistic regression analysis showed that aspect ratio and bifurcation angle were predictors of rupture. Bifurcation angle correlated inversely with inflow coefficient which in turn correlated directly with wall shear stress on Pearson's correlation coefficient Bifurcation angle and aspect ratio were independent predictors for aneurysm rupture.</p>

  143. Text-mining-analysis about outcome in sepsis patients Peer-reviewed

    Kobayashi Naoya, Nakagawa Atsuhiro, Ishigaki Tsukasa, Kudo Daisuke, Niitsuma Kuniyasu, Kawaguchi Tomohiro, Tominaga Teiji, Yamauchi Masanori

    Nihon Shuchu Chiryo Igakukai zasshi 24 (6) 631-632 2017

    Publisher: The Japanese Society of Intensive Care Medicine

    DOI: 10.3918/jsicm.24_631  

  144. Prediction of the initiation of cerebral aneurysms -Progress over view FY2016- Peer-reviewed

    Niizuma K, Yati T, Sugiyama SI, Nakagawa A, Tominaga T

    Proc 3rd Int Symp Multidiscipl Comput Anat A03-KB001 2017

  145. De Novo Development of Moyamoya Disease in an Adult Female with a Genetic Variant of the RNF-213 Gene: Case Report Peer-reviewed

    Ryosuke Tashiro, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Hiroyuki Sakata, Mika Sato-Maeda, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 (1) E8-E11 2017/01

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2016.09.035  

    ISSN:1052-3057

    eISSN:1532-8511

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    Background: The de novo development of moyamoya disease (MMD) in adults is extremely rare, with only 2 cases being previously reported. Furthermore, the mechanisms underlying the progression of adult MMD have not been elucidated yet. Case report: A transient ischemic attack occurred in a 46-year-old woman, owing to progressive MMD. Magnetic resonance (MR) angiography performed 7 years before the diagnosis of MMD did not detect any steno-occlusive changes in the major intracranial vessels, including the internal carotid artery (ICA) and the middle cerebral artery (MCA). However, during the last 2 years, serial MR angiography revealed the gradual progression of left MCA stenosis and ultimately showed apparent stenosis of the bilateral terminal ICA to proximal MCA. Catheter angiography confirmed the definitive diagnosis of MMD. A genetic analysis of RING-finger protein (RNF)-13, an MMD susceptibility gene, revealed that not only the patient, but also her sister, brother, and daughter had the heterozygous variant of the RNF-213 gene. Because of hemodynamic compromise with ischemic symptoms, the patient underwent revascularization surgery on the affected hemisphere, without complications. She had no cerebrovascular event in the postoperative follow-up period of 8 months, and there was no evidence of the further progression of MMD. Conclusion: We herein present the entire clinical course of the de novo development of MMD in a female adult. Newly developed MMD in an adult patient with a characteristic variant of the RNF-213 gene appears to be unique. Key Words: Moyamoya disease-de novo-development-adult-RNF-213 gene. (C) 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  146. Daughter Sac Formation Related to Blood Inflow Jet in an Intracranial Aneurysm Peer-reviewed

    Sin-ichiro Sugiyama, Hidenori Endo, Shunsuke Omodaka, Toshiki Endo, Kuniyasu Niizuma, Sherif Rashad, Toshio Nakayama, Kenichi Funamoto, Makoto Ohta, Teiji Tominaga

    WORLD NEUROSURGERY 96 396-402 2016/12

    Publisher: ELSEVIER SCIENCE INC

    DOI: 10.1016/j.wneu.2016.09.040  

    ISSN:1878-8750

    eISSN:1878-8769

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    OBJECTIVE: We performed a hemodynamic study of an intracranial aneurysm with a newly developed daughter sac during observation to investigate the role of hemodynamics on the formation of a daughter sac. METHODS: A 75-year-old man underwent magnetic resonance angiography that revealed a large internal carotid artery aneurysm with inflow jet inside the aneurysm. The aneurysm was stable for 18 months, but a new daughter sac developed at the tip of the aneurysm during the next 6 months. The daughter sac seemed to be related to the inflow jet on magnetic resonance angiography. Aneurysm geometries before and after daughter sac formation were reconstructed using the longitudinal data of magnetic resonance angiography. Computational fluid dynamic simulations were conducted under the patient-specific pulsatile inlet conditions measured by magnetic resonance velocimetry. RESULTS: The hemodynamic simulation revealed that the inflow jet impinged on 2 sites of the aneurysm: the right side of the aneurysmal dome and the tip of the aneurysm. The flow impingement caused elevation of pressure at both sites. However, the daughter sac formed at the latter site surrounded by the basal cistern but did not form at the former site that was in contact with the right temporal lobe. CONCLUSIONS: Blood inflow jet caused local elevation of pressure, and the formation of the daughter sac occurred at the site with high pressure but without the surrounding structure, which may cancel the perpendicular wall tension.

  147. 食道癌・咽頭癌に関連する感染性仮性総頸動脈破裂の一治療例

    新妻 邦泰, 川口 奉洋, 佐々木 貴史, 藤村 幹, 小川 武則, 香取 幸夫, 松本 康史, 冨永 悌二

    脳血管内治療 1 (Suppl.) S208-S208 2016/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  148. カテーテル先端が離断した二例の検討 Peer-reviewed

    福間 一樹, 重畠 裕也, 矢澤 由加子, 板橋 亮, 鈴木 一郎, 新妻 邦泰, 近藤 竜史, 松本 康史

    脳血管内治療 1 (Suppl.) S215-S215 2016/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  149. Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization Peer-reviewed

    Shin-ichiro Sugiyama, Kuniyasu Niizuma, Kenichi Sato, Sherif Rashad, Misaki Kohama, Hidenori Endo, Toshiki Endo, Yasushi Matsumoto, Makoto Ohta, Teiji Tominaga

    STROKE 47 (10) 2541-2547 2016/10

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1161/STROKEAHA.116.013555  

    ISSN:0039-2499

    eISSN:1524-4628

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    Background and Purpose-Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms. Methods-We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a followup of &gt; 1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics. Results-Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density &lt; 30% were independent and significant predictors for the recanalization of coiled aneurysms. Additional investigation revealed that a small branch angle formed by the basilar artery and the posterior cerebral artery increased blood flow into the aneurysm. Conclusions-The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.

  150. Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula Peer-reviewed

    Hiroyuki Sakata, Miki Fujimura, Kenichi Sato, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 25 (10) E200-E204 2016/10

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2016.07.042  

    ISSN:1052-3057

    eISSN:1532-8511

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    Cerebral proliferative angiopathy (CPA), which is characterized by diffuse vascular abnormalities with intermingled normal brain parenchyma, is a rare clinical entity distinct from classical cerebral arteriovenous malformations. Its pathology at initial state and subsequent course of progression has totally been undetermined. We herein presented a case of a child who was initially diagnosed with deep-seated arteriovenous fistula (AVF), and ultimately developed symptomatic CPA-like vascular lesion over a long period of clinical follow-up. A 7-month-old boy was incidentally found to have an AVF in the right basal ganglia and conservatively followed up. Serial magnetic resonance angiograms revealed the gradual proliferation and enlargement of pial and medullary vessels surrounding the AVF. Seven years later, he had a transient ischemic attack followed by intraventricular hemorrhage. A catheter angiogram showed a diffuse large vascular malformation composed of 2 distinct structures, including AVF in the right basal ganglia and the surrounding proliferated pial and medullary arteries in the right hemisphere. Single-photon emission computed tomography with N-isopropyl[123I]-p-iodoamphetamine revealed apparent hemodynamic compromise on the right hemisphere. Targeted embolization of the pseudoaneurysm originating from the right A1 perforator was performed to prevent rebleeding without complications. The patient had no further cerebrovascular events. Perinidal hypoperfusion induced by a deep-seated AVF could be one of the underlying pathologies of progressive angiogenic activity. This is the first case showing the development of abnormal hemispheric vascular networks mimicking CPA, which offers insight into the pathogenesis of this new entity. (C) 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  151. Long-term follow-up of pediatric moyamoya disease treated by combined direct-indirect revascularization surgery: single institute experience with surgical and perioperative management Peer-reviewed

    Sherif Rashad, Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Teiji Tominaga

    NEUROSURGICAL REVIEW 39 (4) 615-622 2016/10

    Publisher: SPRINGER

    DOI: 10.1007/s10143-016-0734-7  

    ISSN:0344-5607

    eISSN:1437-2320

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    Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that mainly presents in children as cerebral ischemia. Prompt treatment with either a direct or indirect revascularization procedure is necessary for children with MMD in order to prevent repeated ischemic events. We herein present our experience with combined direct and indirect bypass surgery for the treatment of pediatric MMD as well as our uniquely designed perioperative protocol. Twenty-three patients with MMD, aged between 2 and 16 years old (mean 9.36), underwent 38 combined bypass procedures between 2008 and 2015. All patients underwent single superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with encephalo-duro-myo-synangiosis (EDMS). The perioperative management protocol was stratified into two unique eras: the first era with normotensive care and the second era with strict blood pressure control (systolic 100-130 mmHg) and routine aspirin administration. Patients were followed after surgery for a period ranging between 3 and 131 months (mean 77 months) in yearly clinical and radiological follow-ups. Three postoperative complications were observed: two cases of cerebral hyperperfusion (2/38, 5.3 %) and one case of perioperative minor stroke (1/38, 2.6 %), two of which were in the first era. No strokes, either ischemic or hemorrhagic, were observed in the follow-up period, and the activity of daily living as shown by the modified Rankin Scale improved in 20 patients, with no deterioration being observed in any of our patients. STA-MCA bypass with EDMS is safe and effective for the management of pediatric MMD and provides long-term favorable outcomes. Perioperative care with blood pressure control combined with the administration of aspirin may reduce the potential risk of surgical complications.

  152. Ischemic pituitary adenoma apoplexy-Clinical appearance and prognosis after surgical intervention Peer-reviewed

    Yoshikazu Ogawa, Kuniyasu Niizuma, Shunji Mugikura, Teiji Tominaga

    CLINICAL NEUROLOGY AND NEUROSURGERY 148 142-146 2016/09

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.clineuro.2016.07.013  

    ISSN:0303-8467

    eISSN:1872-6968

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    Background: Several retrospective investigations have recommended more passive surgical indications for intratumoral hemorrhage of pituitary adenomas due to probable spontaneous resolution. However, no definitive analyses have compared pituitary adenomas with hemorrhagic apoplexy and intratumoral hemorrhage without evident apoplectic symptoms or pituitary adenoma infarction. Methods: This study retrospectively identified 43 patients with symptomatic pituitary apoplexy among 1067 patients with pituitary adenomas initially treated by surgery at a single institute between April 2005 and May 2015, with 27 cases of hemorrhagic (2.53%) and 16 cases of ischemic apoplexy (1.50%). The inclusion criteria involved evident and sudden onset of symptoms and simultaneous histological confirmation as hemorrhagic or ischemic pituitary apoplexy. Diagnostic differentiation with magnetic resonance (MR) imaging was performed to examine the agreement between MR imaging and histological findings, and the clinical appearance and mid-term prognosis were compared for ischemic pituitary apoplexy and hemorrhagic apoplexy. Results: Diagnostic matching with MR imaging could be performed in 41 of 43 patients (25 with hemorrhagic and 16 with ischemic apoplexy). Agreement with the histological finding was found in 32 of 41 patients overall (78%), 23 of 25 patients with hemorrhagic apoplexy (92%), and 9 of 16 patients with ischemic apoplexy (56%). The main reason for diagnostic discrepancy was thought to be the difficulty in identifying ischemic lesion. All patients in the ischemic group suffered progression of symptoms from initial onset including various cranial nerve palsies, aseptic meningitis, and decreased level of consciousness, whereas the hemorrhagic group suffered progression in 4 of 27 patients. Ischemic group showed a statistically stronger tendency to disease progression than the hemorrhagic group (P &lt; 0.001). Endocrinological examinations showed 4 patients required no hormone supplement therapies but the other 11 patients had persistent hypopituitarism and required hormone supplementation in the ischemic group, whereas 2 of 25 patients required hormone supplementation in the hemorrhagic group. Endocrinological recovery showed a significant difference between the ischemic group and hemorrhagic group (P &lt; 0.01). Conclusions: Ischemic pituitary adenoma apoplexy has a more severe clinical course than hemorrhagic apoplexy. Development of preoperative diagnostic technology to differentiate ischemic from hemorrhagic apoplexy is required to improve the low rate of agreement between the histological and MR imaging findings in patients with ischemic apoplexy. (C) 2016 Elsevier B.V. All rights reserved.

  153. Quantitative Assessment of Circumferential Enhancement along the Wall of Cerebral Aneurysms Using MR Imaging Peer-reviewed

    S. Omodaka, H. Endo, K. Niizuma, M. Fujimura, T. Inoue, K. Sato, S. -I. Sugiyama, T. Tominaga

    AMERICAN JOURNAL OF NEURORADIOLOGY 37 (7) 1262-1266 2016/07

    Publisher: AMER SOC NEURORADIOLOGY

    DOI: 10.3174/ajnr.A4722  

    ISSN:0195-6108

    eISSN:1936-959X

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    BACKGROUND AND PURPOSE: The incidence of wall enhancement of cerebral aneurysms on vessel wall MR imaging has been described as higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms, but the difference in the degree of enhancement between ruptured and unruptured aneurysms is unknown. We compared the degree of enhancement between ruptured and unruptured intracranial aneurysms by using quantitative MR imaging measures. MATERIALS AND METHODS: We performed quantitative analyses of circumferential enhancement along the wall of cerebral aneurysms in 28 ruptured and 76 unruptured consecutive cases by using vessel wall MR imaging. A 3D-T1-weighted fast spin-echo sequence was obtained before and after contrast media injection, and the wall enhancement index was calculated. We then compared characteristics between ruptured and unruptured aneurysms. RESULTS: The wall enhancement index was significantly higher in ruptured than in unruptured aneurysms (1.70 1.06 versus 0.89 +/- 0.88, respectively; P = .0001). The receiver operating characteristic curve analysis found that the most reliable cutoff value of the wall enhancement index to differentiate ruptured from unruptured aneurysms was 0.53 (sensitivity, 0.96; specificity, 0.47). The wall enhancement index remained significant in the multivariate logistic regression analysis (P &lt; .0001). CONCLUSIONS: Greater circumferential enhancement along the wall of cerebral aneurysms correlates with the ruptured state. A quantitative evaluation of circumferential enhancement by using vessel wall MR imaging could be useful in differentiating ruptured from unruptured intracranial aneurysms.

  154. Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease Peer-reviewed

    Atsushi Kanoke, Miki Fujimur, Kuniyasu Niizuma, Taku Fujimura, Aya Kakizaki, Akira Ito, Hiroyuki Sakata, Mika Sato-Maeda, Shigeo Kure, Teiji Tominaga

    BRAIN RESEARCH 1642 1-9 2016/07

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2016.03.009  

    ISSN:0006-8993

    eISSN:1872-6240

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    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD; however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p &lt; 0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD. (C) 2016 Elsevier B.V. All rights reserved.

  155. Prediction of the initiation of cerebral aneurysms -Progress over view FY2015- Peer-reviewed

    Niizuma K, Yati T, Sugiyama SI, Nakagawa A, Tominaga T

    Proc 2nd Int Symp Multidiscipl Comput Anat A03-KB001 2016

  156. Transient middle cerebral artery occlusion in mice induces neuronal expression of RNF213, a susceptibility gene for moyamoya disease Peer-reviewed

    Mika Sato-Maeda, Miki Fujimura, Atsushi Kanoke, Yuiko Morita-Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    BRAIN RESEARCH 1630 50-55 2016/01

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2015.10.055  

    ISSN:0006-8993

    eISSN:1872-6240

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    Although recent genome-wide and locus-specific association studies revealed that the RING finger protein 213 (RNF213) gene is an important susceptibility gene for moyamoya disease (MMD), the exact mechanism by which the genetic alteration of RNF213 contributes to the development of MMD has not yet been elucidated. A quantitative reverse transcription polymerase chain reaction (PCR) analysis revealed that the constitutive expression of the RNF213 gene was very low in adult and embryonic brain tissue. However, information regarding the temporal and spatial expression patterns of the RNF213 gene under the condition of cerebral ischemia, which is one of characteristic pathologies associated with MMD, is currently limited. In order to address this critical issue, Rnf213 mRNA expression was investigated in mouse brains subjected to 60 min of transient middle cerebral artery occlusion (tMCAO). Male C57BL6/j mice underwent tMCAO through the intraluminal blockade of MCA. Expression of the Rnf213 gene in the tMCAO brain was investigated with in situ RNA hybridization and a real-time PCR analysis from 1 to 72 h after tMCAO. In situ RNA hybridization revealed a significant increase in Rnf213 mRNA levels in the cerebral cortex supplied by the affected MCA, especially at the penumbra area, as early as 6 h after tMCAO, and these levels had increased further by 24 h. Rnf213 gene expression remained unchanged in the non-ischemic hemisphere or control specimens. Double staining of Rnf213 mRNA with NeuN immunohistochemisty revealed Rnf213 hybridization signal expression mostly in neurons. The real-time PCR analysis confirmed induction of the Rnf213 gene after tMCAO. Therefore, the Rnf213 gene was up-regulated in the ischemic brain, especially at the penumbra area, 6 h after tMCAO. Early increases in RNF213 gene expression in neurons after tMCAO indicate its involvement in cerebral ischemia, which is an underlying pathology of MMD. Further investigation is required to clarify its exact role in the pathophysiology of MMD. (C) 2015 Elsevier B.V. All rights reserved.

  157. Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation Peer-reviewed

    Hiroki Uchida, Takahiro Morita, Kuniyasu Niizuma, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Hiroyuki Sakata, Yoshiya Matsuzaka, Hajime Mushiake, Teiji Tominaga, Cesario V. Borlongan, Mari Dezawa

    STEM CELLS 34 (1) 160-173 2016/01

    Publisher: WILEY-BLACKWELL

    DOI: 10.1002/stem.2206  

    ISSN:1066-5099

    eISSN:1549-4918

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    Objective: Muse cells reside as pre-existing pluripotent-like stem cells within the fibroblasts, are nontumorigenic, exhibit differentiation capacity into triploblastic-lineage cells, and replenish lost cells when transplanted in injury models. Cell fate and function of human skin fibroblast-derived Muse cells were evaluated in a rat stroke model. Methods: Muse cells (30,000), collected by pluripotent surface marker stage-specific embryonic antigen-3, were injected stereotaxically into three deposits within the rat ischemic cortex at 2 days after transient middle cerebral artery occlusion, and the cells' biological effects were examined for more than 84 days. Results: Muse cells spontaneously and promptly committed to neural/neuronal-lineage cells when cocultured with stroke brain slices. Muse-transplanted stroke rats exhibited significant improvements in neurological and motor functions compared to control groups at chronic days 70 and 84, without a reduction in the infarct size. Muse cells survived in the host brain for up to 84 days and differentiated into NeuN (similar to 65%), MAP-2 (similar to 32%), calbindin (similar to 28%), and GST-pi (similar to 25%)-positive cells in the cortex, but glial fibrillary acidic protein-positive cells were rare. Tumor formation was not observed. Muse cells integrated into the sensory-motor cortex, extended their neurites into cervical spinal cord, and displayed normalized hind limb somatosensory evoked potentials. Interpretation: Muse cells are unique from other stem cells in that they differentiate with high ratio into neuronal cells after integration with host brain microenvironment, possibly reconstructing the neuronal circuit to mitigate stroke symptoms. Human fibroblast-derived Muse cells pose as a novel source of transplantable stem cells, circumventing the need for gene manipulations, especially when contemplating autologous cell therapy for stroke.

  158. Difference in Transcranial Doppler Velocity and Patient Age between Proximal and Distal Middle Cerebral Artery Vasospasms after Aneurysmal Subarachnoid Hemorrhage. International-journal Peer-reviewed

    Misaki Kohama, Shinichiro Sugiyama, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Toshiki Endo, Makoto Ohta, Yasushi Matsumoto, Miki Fujimura, Teiji Tominaga

    Cerebrovascular diseases extra 6 (2) 32-9 2016

    DOI: 10.1159/000447330  

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    BACKGROUND: Transcranial Doppler (TCD) is used to monitor cerebral vasospasm after subarachnoid hemorrhage (SAH), but its diagnostic ability is reported to be limited. Therefore, the purpose of this study was to investigate the relationship between the diagnosability of TCD and the localization of the vasospasm. METHODS: This retrospective study included 20 patients who presented with symptomatic vasospasm after SAH. All 20 patients underwent daily TCD examinations and cerebral angiography after the onset of delayed cerebral ischemia. We defined positive findings on TCD as a maximum flow velocity >200 cm/s or as a mean flow velocity >120 cm/s at the horizontal part of the middle cerebral artery (MCA). We also examined the site of vasospasm on cerebral angiography. RESULTS: Fourteen patients had true-positive findings on TCD examination, and cerebral angiography showed diffuse vasospasm involving the horizontal segment of the MCA. However, 6 patients had false-negative findings on TCD examination, and cerebral angiography showed vasospasm localized at the distal part of the MCA (the insular and/or cortical segments). The patients with proximal vasospasm were significantly younger than those with distal vasospasm. Blood flow velocity at initial TCD and the increase in velocity at the onset of vasospasm were lower and smaller, respectively, in the distal vasospasm group. CONCLUSIONS: In patients with cerebral vasospasm localized at the distal part of the MCA, flow velocity at the horizontal segment of the MCA did not increase to the level we defined as positive. To avoid such false negatives, a slight increase in velocity on TCD should be considered as positive in distal vasospasm cases, especially in older patients.

  159. Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously Peer-reviewed

    Shin-ichiro Sugiyama, Hidenori Endo, Kuniyasu Niizuma, Toshiki Endo, Kenichi Funamoto, Makoto Ohta, Teiji Tominaga

    COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2016 2386031-2386031 2016

    Publisher: HINDAWI PUBLISHING CORP

    DOI: 10.1155/2016/2386031  

    ISSN:1748-670X

    eISSN:1748-6718

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    This was a proof-of-concept computational fluid dynamics (CFD) study designed to identify atherosclerotic changes in intracranial aneurysms. We selected 3 patients with multiple unruptured aneurysms including at least one with atherosclerotic changes and investigated whether an image-based CFD study could provide useful information for discriminating the atherosclerotic aneurysms. Patient-specific geometries were constructed from three-dimensional data obtained using rotational angiography. Transient simulations were conducted under patient-specific inlet flow rates measured by phase-contrast magnetic resonance velocimetry. In the postanalyses, we calculated time-averaged wall shear stress (WSS), oscillatory shear index, and relative residence time (RRT). The volume of blood flow entering aneurysms through the neck and the mean velocity of blood flow inside aneurysms were examined. We applied the age-of-fluid method to quantitatively assess the residence of blood inside aneurysms. Atherosclerotic changes coincided with regions exposed to disturbed blood flow, as indicated by low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The mean velocities of blood inside atherosclerotic aneurysms were lower than those inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older than that in nonatherosclerotic aneurysms, especially near the wall. This proof-of-concept study demonstrated that CFD analysis provided detailed information on the exchange and residence of blood that is useful for the diagnosis of atherosclerotic changes in intracranial aneurysms.

  160. Risk factors for meningitis after craniotomy in patients with subarachnoid hemorrhage due to anterior circulation aneurysms rupture Peer-reviewed

    Takashi Inoue, Hiroaki Shimizu, Miki Fujimura, Kenichi Sato, Hidenori Endo, Kuniyasu Niizuma, Hiroyuki Sakata, Teiji Tominaga

    CLINICAL NEUROLOGY AND NEUROSURGERY 139 302-306 2015/12

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.clineuro.2015.10.029  

    ISSN:0303-8467

    eISSN:1872-6968

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    Objectives: Postoperative meningitis is a serious complication occurring after neurosurgical interventions. However, few investigations have focused specifically on the risk factors that predispose patients to meningitis after major craniotomy. This study identified the risk factors for postoperative meningitis after neurovascular surgery, and investigated the relationship between postoperative meningitis and clinical outcome. Patients and methods: A total of 148 consecutive patients with subarachnoid hemorrhage (SAH) who underwent clipping surgery through a pterional approach within 72 h between January 2007 and September 2011 were retrospectively analyzed. The treatment strategy of our hospital for patients with SAH was based on the findings of digital subtraction angiography in the acute phase. Coil embolization was firstly considered, and clipping through craniotomy if indicated was performed as soon as possible. Prophylactic antibiotics were administered before beginning craniotomy and for at least 3 days after. Hydrocortisone was used to prevent hyponatremia if allowed by the medical condition of the patient. Intrathecal administration of nicardipine hydrochloride was given if required for vasospasm treatment. Meningitis was clinically diagnosed from the blood samplings and cerebrospinal fluid (CSF) examinations. Data were collected from the electronic and paper charts. The status of modified Rankin scale (mRS) 0-2 at discharge was defined as favorable outcome. Results: A total of 14 patients (9.5%) had meningitis during this study period. Symptomatic vasospasm was detected in 33 patients (22.3%), and 12 patients (8.1%) had permanent neurological deficits caused by vasospasm. Overall, 109 patients (73.6%) had favorable outcome. The longer duration of drainage placement, presence of CSF leakage, and intrathecal administration of vasodilatory agent showed significantly higher incidence of postoperative meningitis in univariate analysis (p = 0.0093, 0.0017, and 0.0090, respectively). The proportion of favorable outcome patients at discharge (mRS 0-2) was significantly lower in patients with postoperative meningitis (35.7%) than in patients without it (77.6%) (p = 0.0004). The duration of in-hospital stay was significantly longer in patients with postoperative meningitis (median 58.5, range 28-115 days) than in patients without it (median 38.5, range 19-149 days) (p &lt; 0.001). Multivariate logistic regression analysis showed that only presence of CSF leakage was associated with postoperative meningitis (p = 0.0299). Conclusion: Meningitis after surgery is still a serious complication that requires preventative intervention. The clinical outcome of patients with postoperative meningitis after neurovascular surgery is not still satisfactory. (C) 2015 Elsevier B.V. All rights reserved.

  161. A Case of Small Middle Cerebral Artery (M1) Aneurysm with Rapid Enlargement Peer-reviewed

    Miki Fujimura, Kuniyasu Niizuma, Teiji Tominaga

    Japanese Journal of Neurosurgery 24 (12) 878-882 2015/12

    DOI: 10.7887/jcns.24.878  

  162. Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities Peer-reviewed

    Hiroki Uchida, Hiroyuki Sakata, Miki Fujimura, Kuniyasu Niizuma, Yoshihiro Kushida, Mari Dezawa, Teiji Tominaga

    BRAIN RESEARCH 1629 318-328 2015/12

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2015.10.039  

    ISSN:0006-8993

    eISSN:1872-6240

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    Small subcortical infarcts account for 25% of all ischemic strokes. Although once considered to be a small vessel disease with a favorable outcome, recent studies have reported relatively poor long-term prognoses following small subcortical infarcts. Limited pre-clinical modeling has hampered understanding of the etiology and development of treatments for this disease. Therefore, we attempted to develop a new experimental model of small subcortical infarcts in mice to investigate pathophysiological changes in the corticospinal tract and assess long-term behavioral performance. The vasoconstrictor peptide, endothlin-1 (ET-1), in combination with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), were injected into the internal capsule of mice. Histological and behavioral tests were performed 0-8 weeks after the injection. The ET-1/L-NAME injection resulted in severe neurological deficits that continued for up to 8 weeks. The loss of axons and myelin surrounded by reactive gliosis was identified in the region of the injection, in which the vasoconstriction of microvessels was also observed. Moreover, a tract-tracing study revealed an interruption in axonal flow at the internal capsule. The present model of small subcortical infarcts is unique and novel due to the reproduction of neurological deficits that continue for a long period, up to 8 weeks, as well as the use of mice as experimental animals. The reproducibility, simplicity, and easy adoptability make the present model highly appealing for use in further pre-clinical studies on small subcortical infarcts. (C) 2015 Elsevier B.V. All rights reserved.

  163. Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides Peer-reviewed

    Eikan Mishima, Daisuke Jinno, Yasutoshi Akiyama, Kunihiko Itoh, Shinnosuke Nankumo, Hisato Shima, Koichi Kikuchi, Yoichi Takeuchi, Alaa Elkordy, Takehiro Suzuki, Kuniyasu Niizuma, Sadayoshi Ito, Yoshihisa Tomioka, Takaaki Abe

    PLOS ONE 10 (11) e0143756-e0143756 2015/11

    Publisher: PUBLIC LIBRARY SCIENCE

    DOI: 10.1371/journal.pone.0143756  

    ISSN:1932-6203

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    The biological roles of RNA modifications are still largely not understood. Thus, developing a method for detecting RNA modifications is important for further clarification. We developed a method for detecting RNA modifications called immuno-northern blotting (INB) analysis and herein introduce its various capabilities. This method involves the separation of RNAs using either polyacrylamide or agarose gel electrophoresis, followed by transfer onto a nylon membrane and subsequent immunoblotting using antibodies against modified nucleosides for the detection of specific modifications. We confirmed that INB with the antibodies for 1-methyladenosine (m1A), N6-methyladenosine (m6A), pseudouridine, and 5-methylcytidine (m(5)C) showed different modifications in a variety of RNAs from various species and organelles. INB with the anti-m(5)C antibody revealed that the antibody cross-reacted with another modification on DNA, suggesting the application of this method for characterization of the antibody for modified nucleosides. Additionally, using INB with the antibody for m1A, which is a highly specific modification in eukaryotic tRNA, we detected tRNA-derived fragments known as tiRNAs under the cellular stress response, suggesting the application for tracking target RNA containing specific modifications. INB with the anti-m(6)A antibody confirmed the demethylation of m(6)A by the specific demethylases fat mass and obesity-associated protein (FTO) and ALKBH5, suggesting its application for quantifying target modifications in separated RNAs. Furthermore, INB demonstrated that the knockdown of FTO and ALKBH5 increased the m(6)A modification in small RNAs as well as in mRNA. The INB method has high specificity, sensitivity, and quantitative capability, and it can be employed with conventional experimental apparatus. Therefore, this method would be useful for research on RNA modifications and metabolism.

  164. Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients with Ruptured Supraclinoid Internal Carotid Artery Aneurysms Peer-reviewed

    Hidenori Endo, Miki Fujimura, Hiroaki Shimizu, Takashi Inoue, Kenichi Sato, Kuniyasu Niizuma, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (10) 2358-2368 2015/10

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2015.06.028  

    ISSN:1052-3057

    eISSN:1532-8511

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    Background: Bypass with parent artery trapping is an alternative treatment method for ruptured internal carotid artery (ICA) aneurysms when clipping or coiling is contraindicated. However, the efficacy and safety of this strategy during the acute stage of subarachnoid hemorrhage (SAH) is undetermined. Methods: A retrospective review of 955 consecutive patients presenting SAH between 2006 and 2014 identified 17 patients with ruptured ICA aneurysms treated by bypass with parent artery trapping within 72 hours after the bleeding (bypass group). The 26 cases with ruptured posterior communicating artery aneurysms treated with clipping during the same period were defined as a control group (clipping group). Postoperative cerebral blood flow (CBF) was evaluated by single photon emission computed tomography (SPECT). We analyzed the postoperative hemodynamic status, surgical complications, and the clinical outcomes. Results: Postoperative rebleeding did not occur in any of the cases. CBF in the first postoperative week in the bypass group was lower than that in the clipping group (P = .0165). This CBF decrease improved in the second postoperative week and did not differ from that of the clipping group. The incidence of acute ischemic complications was significantly higher in the bypass group (P = .0284), but the incidence of delayed cerebral ischemia did not differ between the 2 groups. The incidence of favorable outcomes at 6 months was 82.4% in the bypass group and 81% in the clipping group. Conclusions: Although the transient CBF decrease with acute ischemic complications should be noted, acute bypass with parent artery trapping is safe and effective for unclippable/uncoilable ruptured ICA aneurysms.

  165. Temporal profile of the vascular anatomy evaluated by 9.4-tesla magnetic resonance angiography and histological analysis in mice with the R4859K mutation of RNF213, the susceptibility gene for moyamoya disease Peer-reviewed

    Atsushi Kanoke, Miki Fujimura, Kuniyasu Niizuma, Akira Ito, Hiroyuki Sakata, Mika Sato-Maeda, Yuiko Morita-Fujimura, Shigeo Kure, Teiji Tominaga

    BRAIN RESEARCH 1624 497-505 2015/10

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2015.07.039  

    ISSN:0006-8993

    eISSN:1872-6240

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    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology. Recent genome-wide and locus-specific association studies identified the RNF213 gene (RNF213) as an important susceptibility gene of MMD among East Asian populations; however, the mechanism by which an abnormality in RNF213 leads to MMD has not yet been elucidated. Therefore, we herein generated Rnf213-knock-in mice (RNF213-KI) expressing a missense mutation in mouse Rnf213, p. R4828K, on Exon 61, corresponding to human RNF213, p. R4859K, on Exon 60, in MMD patients, and investigated whether they developed MMD. We assessed the temporal profile of intracranial arteries by 9.4-T magnetic resonance angiography (MRA) continuously in the same mouse up to 64 weeks of age. The ratios of the outer diameter of the internal carotid artery (ICA)/basilar artery (BA) and middle cerebral artery (MCA)/BA were evaluated histopathologically. The common carotid arteries (CCA) were sectioned and arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. The results obtained showed that RNF213-KI grew normally, with no significant difference being observed in MBA findings or the anatomy of the circle of Willis between homozygous RNF213-KI and wild-type (Wt) littermates. Furthermore, no significant difference was noted in the diameter of the intracranial vasculature (ICA/BA; p= 0.82, MCA/BA; p =0.27) or in vascular remodeling after CCA ligation. Therefore, RNF213-KI did not spontaneously develop MMD. Multiple secondary insults such as environmental factors may contribute to the onset of MMD in addition to genetic factors. (c) 2015 Elsevier B.V. All rights reserved.

  166. Use of actuator-driven pulsed water jet in brain and spinal cord cavernous malformations resection Peer-reviewed

    Toshiki Endo, Yoko Takahashi, Atsuhiro Nakagawa, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    Clinical Neurosurgery 11 394-403 2015/09/01

    Publisher: Lippincott Williams and Wilkins

    DOI: 10.1227/NEU.0000000000000867  

    ISSN:0148-396X 0069-4827

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    Background: A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. OBJECTIVE: To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. METHODS: Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. RESULTS: The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. CONCLUSION: The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function.

  167. Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection Peer-reviewed

    Toshiki Endo, Yoko Takahashi, Atsuhiro Nakagawa, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga

    OPERATIVE NEUROSURGERY 11 (3) 394-403 2015/09

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1227/NEU.0000000000000867  

    ISSN:2332-4252

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    BACKGROUND: A piezo actuator-driven pulsed water jet (ADPJ) system is a novel surgical instrument that enables dissection of tissue without thermal damage. It can potentially resect intra-axial lesions while preserving neurological function. OBJECTIVE: To report our first experience of applying an ADPJ system to brain and spinal cord cavernous malformations. METHODS: Four patients (2 women and 2 men, mean age 44.5 years) with brain (n = 3) and spinal cord (n = 1) cavernous malformations were enrolled in the study. All surgeries were performed with the aid of the ADPJ system. Postoperative neurological function and radiological findings were evaluated. RESULTS: The ADPJ system was useful in dissecting boundaries between the lesion and surrounding brain/spinal cord tissues. The pulsed water jet provided a clear surgical view and helped surgeons follow the margins. Water jet dissection peeled off the brain and spinal cord tissues from the lesion wall. Surrounding gliotic tissue was preserved. As a consequence, the cavernous malformations were successfully removed. Postoperative magnetic resonance imaging confirmed total removal of lesions in all cases. Preoperative neurological symptoms completely resolved in 2 patients. The others experienced partial recovery. No patients developed new postoperative neurological deficits; facial palsy temporarily worsened in 1 patient who underwent a suprafacial colliculus approach for the brainstem lesion. CONCLUSION: The ADPJ provided a clear surgical field and enabled surgeons to dissect boundaries between lesions and surrounding brain and spinal cord gliotic tissue. The ADPJ system is a feasible option for cavernous malformation surgery, enabling successful tumor removal and preservation of neurological function.

  168. High-grade Cerebral Arteriovenous Malformation Treated with Targeted Embolization of a Ruptured Site: Wall Enhancement of an Intranidal Aneurysm as a Sign of Ruptured Site Peer-reviewed

    Shunsuke Omodaka, Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Kenichi Sato, Yasushi Matsumoto, Teiji Tominaga

    NEUROLOGIA MEDICO-CHIRURGICA 55 (10) 813-817 2015/09

    Publisher: JAPAN NEUROSURGICAL SOC

    DOI: 10.2176/nmc.cr.2015-0052  

    ISSN:0470-8105

    eISSN:1349-8029

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    Partial targeted embolization of the ruptured site of cerebral arteriovenous malformations (AVMs) is considered effective to prevent rebleeding. The site of rupture is usually determined by morphological features, such as an intranidal aneurysm or a venous varix; however, the site can be difficult to identify in high-grade AVM with complicated angioarchitecture. The authors present a case of a 36-year-old woman with high-grade AVM presented with repeated hemorrhage. Cerebral angiography showed intranidal aneurysm, which was considered the ruptured site. The T-1-weighted imaging with gadolinium enhancement demonstrated linear enhancement along the outer surface of the thickened wall of the intranidal aneurysm, which could be supplementary information to identify the ruptured site. Obliteration of the intranidal aneurysm was successfully achieved by emergent targeted embolization using N-butyl cyanoacrylate. The patient recovered and regained an independent status. The patient underwent volume-staged radiosurgery and experienced no further hemorrhage during the 26 months follow-up. Targeted embolization of the ruptured site is considered effective to prevent rebleeding in high-grade cerebral AVMs. Wall enhancement of the intranidal aneurysm, in addition to the structural characteristics, could be helpful in identifying the site of rupture embedded in the complicated angioarchitecture.

  169. Ruptured Cerebral Microaneurysm Diagnosed by 3-Dimensional Fast Spin-Echo T1 Imaging with Variable Flip Angles Peer-reviewed

    Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Kenichi Sato, Takashi Inoue, Shin-ichiro Osawa, Teiji Tominaga

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (8) E231-E235 2015/08

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.jstrokecerebrovasdis.2015.04.031  

    ISSN:1052-3057

    eISSN:1532-8511

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    Cerebral microaneurysms, which are 2 mm or small in size, are a rare cause of subarachnoid hemorrhage (SAH). The authors present 2 cases with ruptured microaneurysms, in which 3-dimensional (3D) fast spin-echo T1 imaging with variable flip angles (CUBE T1) using gadolinium-diethylenetriaminepentaacetic acid (Gd) enhancement was useful in diagnosing the microaneurysms as the source of bleeding. Case 1 was a 61-year-old woman who had an SAH localized to the left Sylvian fissure. A small bulge (1.4 mm) at the bifurcation of left middle cerebral artery (MCA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was successfully treated by trapping of the lower division of the left M2 segment with superficial temporal artery-M3 bypass. The intraoperative findings indicated that the microaneurysm at the bifurcation of the left MCA was the ruptured site. Case 2 was a 41-year-old man who had a diffuse SAH. A small bulge (1.5 mm) at the inferolateral wall of the left internal carotid artery (ICA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was treated by trapping of the left ICA with external carotid artery-saphenous vein graft-M2 bypass without complications. The intraoperative findings indicated that the microaneurysm at the inferolateral wall of the left ICA was the ruptured site. CUBE T1 with Gd enhancement was useful as an adjunctive tool for the diagnosis of ruptured cerebral microaneurysms. This sequence might enable neurosurgeons to perform curative surgery with certainty for ruptured microaneurysms.

  170. Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia Peer-reviewed

    Yasuo Nishijima, Kuniyasu Niizuma, Miki Fujimura, Yosuke Akamatsu, Hiroaki Shimizu, Teiji Tominaga

    JOURNAL OF NEUROSURGERY 123 (1) 243-253 2015/07

    Publisher: AMER ASSOC NEUROLOGICAL SURGEONS

    DOI: 10.3171/2014.9.JNS14778  

    ISSN:0022-3085

    eISSN:1933-0693

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    OBJECT Numerous studies have attempted to reveal the pathophysiology of ischemic neuronal injury using a representative transient global cerebral ischemia (tGCI) model in rodents; however, most of them have used gerbil or rat models. Recent advances in transgene and gene-knockout technology have enabled the precise molecular mechanisms of ischemic brain injury to be investigated. Because the predominant species for the study of genetic mutations is the mouse, a representative mouse model of tGCI is of particular importance. However, simple mouse models of tGC1 are less reproducible; therefore, a more complex process or longer duration of ischemia, which causes a high mortality rate, has been used in previous tGCI models in mice. In this study, the authors aimed to overcome these problems and attempted to produce consistent unilateral delayed hippocampal CA1 neuronal death in mice. METHODS C57BL/6 mice were subjected to short-term unilateral cerebral ischemia using a 4-mm silicone-coated intraluminal suture to obstruct the origin of the posterior cerebral artery (PCA), and regional cerebral blood flow (rCBF) of the PCA territory was measured using laser speckle flowmetry. The mice were randomly assigned to groups of different ischemic durations and histologically evaluated at different time points after ischemia. The survival rate and neurological score of the group that experienced 15 minutes of ischemia were also evaluated. RESULTS Consistent neuronal death was observed in the medial CA1 subregion 4 days after 15 minutes of ischemia in the group of mice with a reduction in rCBF of &lt; 65% in the PCA territory during ischemia. Morphologically degenerated cells were mostly positive for terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling and cleaved caspase 3 staining 4 days after ischemia. The survival rates of the mice 24 hours (n = 24), 4 days (n = 15), and 7 days (n = 7) after being subjected to 15 minutes of ischemia were 95.8%, 100%, and 100%, respectively, and the mice had slight motor deficits. CONCLUSIONS The authors established a model of delayed unilateral hippocampal neuronal death in C57BL16 Mice by inducing ischemia in the PCA territory using an intraluminal suture method and established inclusion criteria for PCA-territory rCBF monitored by laser speckle flowmetry. This model may be useful for investigating the precise molecular mechanisms of ischemic brain injury.

  171. Analysis of Rupture during Follow-up of Unruptured Aneurysm Peer-reviewed

    Shinya KOYAMA, Mizuho INOUE, Hiroki UCHIDA, Kuniyasu NIIZUMA, Atsushi SAITO, Hiroyuki KON, Tatsuya SASAKI, Michiharu NISHIJIMA

    Neurological Surgery 43 (6) 523-529 2015/06/10

    DOI: 10.11477/mf.1436203064  

  172. Blood Pressure Lowering and Minocycline Administration as Secure and Effective Postoperative Management after Revascularization Surgery for Moyamoya Disease Peer-reviewed

    Miki FUJIMURA, Kuniyasu NIIZUMA, Hidenori ENDO, Kenichi SATO, Takashi INOUE, Teiji TOMINAGA

    Surgery for Cerebral Stroke 43 (2) 136-140 2015/03

    Publisher: None

    DOI: 10.2335/scs.43.136  

    ISSN:0914-5508

    eISSN:1880-4683

  173. Quantitative analysis of early postoperative cerebral blood flow contributes to the prediction and diagnosis of cerebral hyperperfusion syndrome after revascularization surgery for moyamoya disease Peer-reviewed

    Miki Fujimura, Kuniyasu Niizuma, Hidenori Endo, Kenichi Sato, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

    NEUROLOGICAL RESEARCH 37 (2) 131-138 2015/02

    Publisher: MANEY PUBLISHING

    DOI: 10.1179/1743132814Y.0000000432  

    ISSN:0161-6412

    eISSN:1743-1328

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    Objective: Cerebral hyperperfusion syndrome (HPS) is a potential complication of extracranial-intracranial (EC-IC) bypass for moyamoya disease; however, the pathological threshold of the early cerebral blood flow (CBF) increases after EC-IC bypass has yet to be determined. The purpose of this study is to evaluate the predictive and diagnostic values of early quantitative CBF analysis for the detection of HPS after EC-IC bypass for moyamoya disease. Methods: We quantitatively evaluated regional CBF at the site of the anastomosis in 23 patients with moyamoya disease aged between 18 and 66 years (mean, 39.6) before and 1 day after superficial temporal artery-middle cerebral artery anastomosis by an auto-radiographic method using N-isopropyl-p-[I-123] iodoamphetamine single-photon emission computed tomography. Results: Regional CBF 1 day after surgery was significantly higher in patients with HPS (n = 5; mean, 54.6 ml/100 g/minutes) than in patients without HPS (n = 18; mean, 40.5 ml/100 g/minutes) (P = 0.038). The postoperative/preoperative CBF ratio was significantly higher in patients with HPS (1.84) than in patients without HPS (1.34) (P = 0.044). Multivariate analyses showed that the regional CBF value 1 day after surgery (P = 0.036) and operating on the left hemisphere (P = 0.026) significantly correlated with HPS. All patients with HPS developed symptoms and/or intracerebral hemorrhage more than 2 days after EC-IC bypass. Receiver operating characteristic analysis indicated that the cutoff value of pathological postoperative CBF increase was 46.1 ml/100 g/minutes (sensitivity = 80%, specificity = 77.8%, AUC value = 0.81). Conclusion: Quantitative analysis of early postoperative CBF is useful for predicting and diagnosing HPS after revascularization surgery for moyamoya disease.

  174. Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease Peer-reviewed

    Akira Ito, Miki Fujimura, Kuniyasu Niizuma, Atsushi Kanoke, Hiroyuki Sakata, Yuiko Morita-Fujimura, Atsuo Kikuchi, Shigeo Kure, Teiji Tominaga

    BRAIN RESEARCH 1594 310-320 2015/01

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2014.11.014  

    ISSN:0006-8993

    eISSN:1872-6240

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    Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology that is characterized by the development of abnormal vascular networks at the base of the brain. Recent genome-wide studies identified RNF213 as an important MMD susceptibility gene. However, the exact mechanism by which the RNF213 abnormality leads to MMD remains unknown. Thus, we sought to clarify the role of RNF213 in angiogenesis under ischemic conditions using conventional RNF213 knockout mice. We assessed the infarction volume, cerebral edema, and vascular density in the ischemic brain after transient middle cerebral artery occlusion (tMCAO). To further evaluate systemic angiogenesis following chronic ischemia, we investigated blood flow recovery using laser speckle flowmetry, the severity of ambulatory impairments, and vascular density in the hind-limb after permanent femoral artery ligation. Results were compared between homozygous RNF213 knockout mice (RNF213 -/-) and wild-type littermates (Wt). No significant differences were observed in infarction volume or the formation of edema following tMCAO, or in vascular density 28 days after tMCAO between RNF213 -/- and Wt. Blood flow recovery was significantly improved in RNF213 -/- from 3 to 28 days after femoral artery ligation, and angiogenesis as shown by vascular density in the hind-limb was significantly enhanced in RNF213 -/- at 28 days. The amelioration of ambulatory impairments was also evident in RNF213 -/-. Angiogenesis was enhanced in mice lacking RNF213 after chronic hind-limb ischemia, which suggested the potential role of the RNF213 abnormality in the development of pathological vascular networks in chronic ischemia. (C) 2014 Elsevier B.V. All rights reserved.

  175. 動脈硬化性変化をきたした未破裂脳動脈瘤5例の検討 Peer-reviewed

    杉山 慎一郎, 遠藤 英徳, 新妻 邦泰, 清水 宏明, 長嶺 義秀, 藤原 悟, 冨永 悌二

    東北脳血管障害研究会学術集会記録集 36回 186-204 2014/12

    Publisher: None

    ISSN:1880-9278

  176. Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility gene Peer-reviewed

    Shinya Sonobe, Miki Fujimura, Kuniyasu Niizuma, Taku Fujimura, Sadanori Furudate, Yasuo Nishijima, Shigeo Kure, Teiji Tominaga

    NEUROREPORT 25 (18) 1442-1446 2014/12

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1097/WNR.0000000000000289  

    ISSN:0959-4965

    eISSN:1473-558X

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    Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology. Recent genetic studies have identified RNF213 as an important susceptibility gene for MMD. To evaluate the role of RNF213 in vascular remodeling, RNF213 knockout mice (RNF213-/-) and their wild-type littermates (WT) were subjected to common carotid artery ligation to induce vascular hyperplasia. We examined the vascular expression of matrix metalloproteinase (MMP)-9, known to be increased in MMD. MMP-9 expression was significantly higher in RNF213-/- mice than in wild-type mice 1 and 7 days after common carotid artery ligation. The vascular wall was significantly thinner in RNF213-/- mice at 14 days. The increased vascular expression of MMP-9 and subsequent vascular wall thinning in RNF213-/-mice could reflect the early characteristic of MMD, consistent with the recently proposed constrictive remodeling theory. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

  177. Maximum Preservation of the Media in Carotid Endarterectomy Peer-reviewed

    Kuniyasu Niizuma, Hiroaki Shimizu, Takashi Inoue, Mika Watanabe, Teiji Tominaga

    NEUROLOGIA MEDICO-CHIRURGICA 54 (10) 812-818 2014/10

    Publisher: JAPAN NEUROSURGICAL SOC

    DOI: 10.2176/nmc.tn.2014-0202  

    ISSN:0470-8105

    eISSN:1349-8029

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    Carotid endarterectomy (CEA) is intended to remove atheromatous plaque by dissecting a plane between the intima and the media (circular medial fibers), but this may not be the optimal dissection plane. The present technique is based on identifying the plane that divides the media from the plaque, so preserving the media on the adventitia as much as possible. This plane is more difficult to find and follow than the easy-to-dissect plane usually located between the media and the adventitia, because the plaque invades the media and so the dividing plane is located within the media. In this prospective observational study, CEA was performed in 22 patients to histologically examine the excised plaques and small samples of the whole arterial wall, and evaluate the clinical outcomes. Plaque had invaded the luminal part of the media in the whole arterial wall sample of 80% of cases. Thin medial layers covering &gt; 80% of the surface of the plaque were found in 16 of 22 plaques (73%). Some atheromatous component was sometimes left in the preserved media, rather than completely removed with the media. No morbidity or mortality had occurred by discharge. Only 1 small ipsilateral infarction (4.5%) and no restenosis of greater than 50% were detected during the mean follow-up period of 7 years. Since the plaque usually invades the media, the optimum dissection plane may be located within the media, dividing it into two layers. The presence of some remnant atheromatous components in the preserved media was not associated with surgical complications or restenosis.

  178. Intraoperative Monitoring for Carotid Endarterectomy Using Regional Saturation of Oxygen, Motor Evoked Potential and Somatosensory Evoked Potential: Reference to Necessity of Internal Shunt Peer-reviewed

    Shinya KOYAMA, Masashi CHONAN, Kuniyasu NIIZUMA, Hiroyuki KON, Makoto ABE, Shintaro MATSUO, Tatsuya SASAKI, Michiharu NISHIJIMA

    Surgery for Cerebral Stroke 42 (5) 340-346 2014/09

    DOI: 10.2335/scs.42.340  

  179. AVMに対する治療戦略 -血管内治療医の立場から- Peer-reviewed

    松本 康史, 近藤 竜史, 新妻 邦泰, 遠藤 英徳, 藤原 悟, 高橋 明, 冨永 悌二

    The Mt.Fuji Workshop on CVD 32 50-53 2014/08

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    ISBN:0289-8438

  180. SMTP-7, a new thrombolytic agent, decreases hemorrhagic transformation after transient middle cerebral artery occlusion under warfarin anticoagulation in mice Peer-reviewed

    Akira Ito, Kuniyasu Niizuma, Hiroaki Shimizu, Miki Fujimura, Keiji Hasumi, Teiji Tominaga

    BRAIN RESEARCH 1578 38-48 2014/08

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2014.07.004  

    ISSN:0006-8993

    eISSN:1872-6240

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    Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a new thrombolytic agent that exhibits anti-inflammatory effects. We previously demonstrated that the hemorrhagic transformation was fewer with SMTP-7 than with recombinant tissue plasminogen activator (rt-PA) following ischemia-reperfusion in animal models. We hypothesized that SMTP-7 may decrease hemorrhagic transformation after ischemia-reperfusion under the warfarin-treated condition. Transient middle cerebral artery occlusion (MCAO) was induced for 3 h using an intraluminal suture in warfarin-treated mice to produce hemorrhagic transformation. Warfarin was administered orally for a 24-h feeding period before MCAO through bottled drinking water (5 mg in 375 ml tap water), resulting in a mean INR of 5.6 +/- 0.2. Mice were treated with vehicle, rt-PA, or SMTP-7 5 h before reperfusion. Twenty percent of vehicle-treated and 50.0% of rt-PA-treated mice died 24 h after reperfusion, while all SMTP-7-treated mice survived. Hemorrhagic severity in SMTP-7-treated mice was significantly lower than that in rt-PA-treated mice. Neurological deficit was significantly lower in SMTP-7-treated mice than vehicle- and rt-PA-treated mice. These results indicate that SMTP-7 decreases mortality, hemorrhagic transformation, and neurological deficits, and can be a safe thrombolytic agent following MCAO under the warfarin-treated condition. (C) 2014 Elsevier B.V. All rights reserved.

  181. Development of a de novo arteriovenous malformation after bilateral revascularization surgery in a child with moyamoya disease Case report Peer-reviewed

    Miki Fujimura, Naoto Kimura, Masayuki Ezura, Kuniyasu Niizuma, Hiroshi Uenohara, Tem Tominaga

    JOURNAL OF NEUROSURGERY-PEDIATRICS 13 (6) 647-649 2014/06

    Publisher: AMER ASSOC NEUROLOGICAL SURGEONS

    DOI: 10.3171/2014.3.PEDS13610  

    ISSN:1933-0707

    eISSN:1933-0715

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    The development of a de novo arteriovenous malformation (AVM) in patients with moyamoya disease is extremely rare. A 14-year-old girl developed an AVM in the right occipital lobe during the 4-year postoperative period following successful bilateral revascularization surgeries. She suffered a transient ischemic attack with hemodynamic compromise of the bilateral hemispheres at the age of 10 years. Results of an initial examination by 1.5-T MRI and MR angiography satisfied the diagnostic criteria of moyamoya disease but failed to detect any vascular malformation. Bilateral direct and indirect revascularization surgeries in the anterior circulation relieved her symptoms, and she underwent MRI and MR angiography follow-up every year after surgery. Serial T2-weighted MRI revealed the gradual appearance of flow voids in the right occipital lobe during the follow-up period. Magnetic resonance angiography ultimately indicated the development of an AVM 4 years after these surgeries when catheter angiography confirmed the diagnosis of an AVM in the right occipital lobe. The AVM remained asymptomatic, and the patient remained free of cerebrovascular events during the time she was observed by the authors. Acquired AVM in moyamoya disease is extremely rare, with only 3 pediatric cases including the present case being reported in the literature. The development of a de novo AVM in a postoperative patient with moyamoya disease appears to be unique, and this case may provide insight into the dynamic pathology of AVMs.

  182. Coil embolization of the growing unruptured intracranial aneurysms for patients aged 80 years or older - important points and tips of the coil embolization in elderly patients Peer-reviewed

    Ichiro SUZUKI, Yasushi MATSUMOTO, Kuniyasu NIIZUMA, Ryushi KONDO, Hidenori ENDO, Satoru FUJIWARA, Akira TAKAHASHI, Hiroaki SHIMIZU, Teiji TOMINAGA

    JNET: Journal of Neuroendovascular Therapy 8 (1) 14-20 2014/03

    DOI: 10.5797/jnet.or.13036  

    ISSN:1882-4072

  183. Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance angiography and histopathological analysis in mice lacking RNF213: A susceptibility gene for moyamoya disease Peer-reviewed

    Shinya Sonobe, Miki Fujimura, Kuniyasu Niizuma, Yasuo Nishijima, Akira Ito, Hiroaki Shimizu, Atsuo Kikuchi, Natsuko Arai-Ichinoi, Shigeo Kure, Teiji Tominaga

    BRAIN RESEARCH 1552 64-71 2014/03

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.brainres.2014.01.011  

    ISSN:0006-8993

    eISSN:1872-6240

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    Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology. Recent genome-wide and locus-specific association studies identified RNF213 as an important MMD susceptibility gene. However, the exact mechanism by which an abnormality in RNF213 leads to MMD is unknown. To evaluate the role of RNF213 in the etiology of MMD, we generated RNF213-deficient mice (RNF213 -/-) by deleting exon 32 of RNF213 by the Cre-lox system, and investigated whether they developed MMD. The temporal profile of cervical/intracranial arteries was evaluated by 9.4-T magnetic resonance angiography (MRA). The anatomy of the circle of Willis was analyzed by a transcardiac injection of carbon black dye. The common carotid arteries (CCA) were sectioned and the arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. As a result, RNF213 -/- grew normally, and no significant difference was observed in MRA findings, the anatomy of the circle of Willis, or vascular wall thickness/thinness between RNF -/- and wild-type littermates (Wt.) under normal conditions until 64 weeks of age. However, Elastica-Masson staining demonstrated that both the intima and medial layer were significantly thinner after CCA ligation in RNF213 -/- than in Wt. after 14 days (P &lt;0.01). In conclusion, mice lacking the RNF213 gene did not spontaneously develop MMD, indicating that a functional loss of RNF213 did not sufficiently induce MMD. Suppression of vascular remodeling in RNF213 -/- requires further examination to clarify the role of RNF213. (c) 2014 Elsevier B.V. All rights reserved.

  184. Minocycline Prevents Focal Neurological Deterioration Due to Cerebral Hyperperfusion After Extracranial-Intracranial Bypass for Moyamoya Disease Peer-reviewed

    Miki Fujimura, Kuniyasu Niizuma, Takashi Inoue, Kenichi Sato, Hidenori Endo, Hiroaki Shimizu, Teiji Tominaga

    NEUROSURGERY 74 (2) 163-170 2014/02

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1227/NEU.0000000000000238  

    ISSN:0148-396X

    eISSN:1524-4040

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    BACKGROUND:Cerebral hyperperfusion (CHP) is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), and optimal postoperative management has not yet been established. Minocycline, a neuroprotective antibiotic agent, plays a role in blocking matrix metalloproteinase 9 (MMP-9), which contributes to edema formation and hemorrhagic conversion after cerebral ischemia-reperfusion. Patients with MMD have been shown to have increased serum MMP-9 levels.OBJECTIVE:To examine the effect of minocycline on the prevention of postoperative CHP after STA-MCA anastomosis for MMD.METHODS:N-isopropyl-p-[I-123]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 109 hemispheres in 86 consecutive patients with MMD (ages, 9-69 years; mean, 37.2 years). Postoperative systolic blood pressure was strictly maintained at lower than 130 mm Hg in all 109 surgeries. The most 60 recent hemispheres were managed by the intraoperative and postoperative intravenous administration of minocycline hydrochloride (200 mg/d). The incidence of focal neurological deterioration (FND) due to CHP was then compared with that in 36 patients undergoing 49 surgeries managed without minocycline.RESULTS:FND due to CHP was observed in 4 operated hemispheres in patients treated without minocycline (4/49, 8.16%), and in none in the minocycline-treated group (0/60) (P = .0241). Multivariate analysis revealed that minocycline administration (P &lt; .001), surgery on the left hemisphere (P = .031), and a smaller recipient artery diameter (P &lt; .001) significantly correlated with FND due to CHP.CONCLUSION:The administration of minocycline with strict blood pressure control may represent secure and effective postoperative management to prevent symptomatic CHP after STA-MCA anastomosis for MMD.ABBREVIATIONS:CBF, cerebral blood flowCHP, cerebral hyperperfusionEC-IC, extracranial-intracranialEDMS, encephaloduromyosynangiosisFND, focal neurological deterioration(123)I-IMP-SPECT,N-isopropyl-p-[I-123]iodoamphetamine single-photon emission computed tomographyMCA, middle cerebral arteryMMD, moyamoya diseaseMMP-9, matrix metalloproteinase 9MRA, magnetic resonance angiographySPECT, single-photon emission computed tomographySTA-MCA, superficial temporal artery-middle cerebral artery

  185. Hemodynamic analysis of intracranial aneurysms with atherosclerosis Peer-reviewed

    Shinichiro Sugiyama, K. Funamoto, T. Nakayama, K. Niizuma, T. Tominaga

    IFMBE Proceedings 43 738-740 2014

    Publisher: Springer Verlag

    DOI: 10.1007/978-3-319-02913-9_188  

    ISSN:1680-0737

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    Intracranial aneurysms can have atherosclerotic wall properties that may be important in predicting aneurysm history. This study aimed to investigate hemodynamic characteristics of atherosclerotic legions in intracranial aneurysms. We conducted computational fluid dynamic analyses of 30 aneurysms using patient-derived geometries and inlet flow rates. Among 30 aneurysms, seven atherosclerotic lesions with remarkable yellow lipid deposition were identified in five aneurysms. All seven atherosclerotic lesions were spatially agreed with the area exposed to stagnant blood flow. Univariate analysis revealed that male (P = 0.031), cigarette smoking (P = 0.047) and the exposure to stagnant blood flow (P = 0.024) are significantly related to atherosclerotic lesion formation on the aneurysmal wall. Of those variables that influenced atherogenesis, the variable male (P = 0.0046) and the exposure to stagnant flow (P = 0.0037) remained significant in the multivariate regression model. In conclusion, male sex and stagnant blood flow inside aneurysms were independent risk factors for atherosclerosis in intracranial aneurysms.

  186. Issues in Revascularization Surgery for Elderly Patients with Moyamoya Disease Peer-reviewed

    Miki FUJIMURA, Hiroaki SHIMIZU, Takashi INOUE, Kuniyasu NIIZUMA, Teiji TOMINAGA

    Surgery for Cerebral Stroke 42 (1) 37-41 2014/01

    DOI: 10.2335/scs.42.37  

    ISSN:0914-5508

  187. Cervical perimedullary arteriovenous shunts: A study of 22 consecutive cases with a focus on angioarchitecture and surgical approaches Peer-reviewed

    Toshiki Endo, Hiroaki Shimizu, Kenichi Sato, Kuniyasu Niizuma, Ryushi Kondo, Yasushi Matsumoto, Akira Takahashi, Teiji Tominaga

    Neurosurgery 75 (3) 238-249 2014

    Publisher: Lippincott Williams and Wilkins

    DOI: 10.1227/NEU.0000000000000401  

    ISSN:1524-4040 0148-396X

    eISSN:1524-4040

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    BACKGROUND:: Reports of cervical perimedullary arteriovenous shunt (PMAVS) are limited, and treatment strategies have not been established. OBJECTIVE:: To describe angioarchitecture and optimal treatment strategies for cervical PMAVS. METHODS:: We treated 22 patients with cervical PMAVS between 2000 and 2012 (8 women and 14 men age, 9-80 years). According to the classification, our patients included type IVa (4 patients), type IVb (16 patients), and type IVc (2 patients). Seventeen patients presented with subarachnoid hemorrhage. RESULTS:: A total of 41 shunting points were localized in 22 patients, of which 34 points were located ventral or ventrolateral to the spinal cord. The anterior spinal artery (ASA) contributed to the shunts in 16 patients. Aneurysm formation was identified in 8 patients. Endovascular treatment was attempted in 3 patients, resulting in complete obliteration in 1 patient (type IVc). Overall, 21 patients underwent open surgery. An anterior approach with corpectomy was elected for 2 patients the other 19 patients underwent the posterior approaches using indocyanine green videoangiography, intraoperative angiography, endoscopy (8 patients), and neuromonitoring. Twenty patients were rated as having a good recovery at 6 months after surgery. No recurrence was observed in any patients during the follow-up (mean, 59.7 months). CONCLUSION:: Shunting points of the cervical PMAVS were predominantly located ventral or ventrolateral to the spinal cord and were often fed by the ASA. Even for ventral lesions, posterior exposure assisted with neuromonitoring and endoscopy, and intraoperative angiography provided a view sufficient to understand the relationships between the shunts and the ASA and contributed to good surgical outcomes. Copyright © Congress of Neurological Surgeons.

  188. Signal changes on T2*-weighted magnetic resonance imaging from the acute to chronic phases in patients with subarachnoid hemorrhage Peer-reviewed

    Takashi Inoue, Shihomi Takada, Hiroaki Shimizu, Kuniyasu Niizuma, Miki Fujimura, Kenichi Sato, Hidenori Endo, Teiji Tominaga

    Cerebrovascular Diseases 36 (5-6) 421-429 2013/12

    DOI: 10.1159/000355897  

    ISSN:1015-9770 1421-9786

    eISSN:1421-9786

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    Background: Timing of the onset of subarachnoid hemorrhage (SAH) is important for treatment decision-making, especially as some patients visit hospital several weeks after the onset of SAH. T2*-weighted (T2*W) magnetic resonance (MR) imaging is regarded as a sensitive method for the detection of deoxyhemoglobin or hemosiderin deposits. This study investigated the characteristics of the abnormal low intensity changes on T2*W imaging in patients with SAH, how long the abnormal low intensity persisted, and whether the day of onset could be predicted based on the T2*W imaging changes. Methods: The study included patients treated for SAH associated with ruptured cerebral aneurysms, or who had previously suffered such SAH and were followed up at our hospital, between 2006 and 2007. MR imaging was performed using a whole-body 3.0-tesla MR scanner. All patients underwent gradient recalled echo (GRE) and echo planar (EP) T2*W imaging. The strength of the low intensity areas was evaluated as the following 5 grades: grade 0, no abnormal low intensity on both GRE and EP T2*W images grade 1, no abnormal intensity on GRE T2*W images and low intensity on EP T2*W images grade 2, spotty abnormal low intensity on both GRE and EP T2*W images grade 3, medium abnormal low intensity (&lt 5 mm) on both GRE and EP T2*W images, and grade 4, large abnormal low intensity (≥5 mm) on both GRE and EP T2*W images. Results: A total of 50 patients with 74 MR images were included during the study period. Abnormal low intensity on T2*W imaging was observed in all patients. The T2* score gradually decreased from the onset of SAH until day 90, showing a significant negative linear correlation (R2 = 0.25, p = 0.0002). On the other hand, the T2* score did not change after 1 year. The square correlation coefficient between the recorded and calculated days from the onset of SAH was 0.29 (p = 0.0107). The pure error was ±10 days. Conclusion: The T2* score gradually decreased until 90 days from the onset of SAH, but persisted for 16 years after the onset. We could predict the day of onset with pure error ±10 days in patients with SAH within 90 days of onset using our grading system for T2*W images. © 2013 S. Karger AG, Basel.

  189. Surgical Treatment of Spinal Extradural Arteriovenous Fistula With Parenchymal Drainage: Report on 5 Cases Peer-reviewed

    Kuniyasu Niizuma, Toshiki Endo, Kenichi Sato, Shihomi Takada, Takayuki Sugawara, Shigeki Mikawa, Teiji Tominaga

    NEUROSURGERY 73 (ONS Suppl 2) E287-E293 2013/12

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1227/NEU.0000000000000189  

    ISSN:0148-396X

    eISSN:1524-4040

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    BACKGROUND AND IMPORTANCE: Spinal extradural arteriovenous fistula (SEDAVF) with parenchymal drainage (type A) is a rare clinical entity that causes venous congestive myelopathy. Treatment includes endovascular and open microsurgical interventions. We reviewed the clinical records of patients treated for a type A SEDAVF to evaluate the feasibility of our treatment strategy. CLINICAL PRESENTATION: Between 2004 and 2010, 5 patients with a type A SEDAVF were treated at our institutes (4 men and 1 woman; mean age, 60 years). We performed endovascular transvenous embolization (TVE) when lesions were accessible transvenously; otherwise, microsurgical perimedullary drainer occlusion was performed. Follow-up ranged from 23 to 94 months (mean, 45.8 months). One patient was treated with TVE, and the remaining 4 were treated with microsurgical drainer occlusion. After a simple intradural drainer occlusion, an epidural venous lake was completely thrombosed in 2 patients. In 1 patient, postoperative angiography revealed that a part of the epidural component had persisted; however, the patient has been asymptomatic. In the remaining case with multiple intradural draining veins, sole drainer occlusion was not sufficient. A second surgery was required to meticulously coagulate the venous lake. As a consequence, parenchymal drainers disappeared. Overall, all patients stabilized or improved neurologically and experienced no recurrence. CONCLUSION: To treat a type A SEDAVF, either TVE or microsurgical intradural drainer occlusion can be used for satisfactory long-term results with minimal surgical risks. For a case with multiple intradural draining veins, detachment of the venous lake should be considered.

  190. Efficacy of fusion image for the preoperative assessment of anatomical variation of the anterior choroidal artery Peer-reviewed

    Yasuko Aoki, Hidenori Endo, Kuniyasu Niizuma, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

    Neurological Surgery 41 (12) 1075-1080 2013/12

    ISSN:0301-2603 1882-1251

    eISSN:1882-1251

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    We report two cases with internal carotid artery (ICA) aneurysms, in which fusion image effectively indicated the anatomical variations of the antenor choroidal artery (AchoA) Fusion image was obtained using fusion application software (Integrated Registration, Advantage Workstation VS4, GE Healthcare). When the artery passed through the choroidal fissure, it was diagnosed as AchoA Case 1 had an aneurysm at the left ICA Left internal carotid angiography (ICAG) showed that an artery arising from the aneurysmal neck supplied the medial occipital lobe Fusion image showed that this artery had a branch passing through the choroidal fissure, which was diagnosed as hyperplastic AchoA Case 2 had an aneurysm at the supraclinoid segment of the right ICA AchoA or postenor communicating artery (PcomA) were not detected by the right ICAG Fusion image obtained from 3D vertebral angiography (VAG) and MRI showed that the right AchoA arose from the nght PcomA Fusion image obtained from the right ICAG and the left VAG suggested that the aneurysm was located on the ICA where the PcomA regressed. Fusion image is an effective tool for assessing anatomical vanations of AchoA The present method is simple and quick for obtaining a fusion image that can be used in a real-time clinical setting.

  191. Stagnant Blood Flow in Intracranial Aneurysms: A Possible Association with Atherosclerosis

    Shin-ichiro Sugiyama, Toshio Nakayama, Kenichi Funamoto, Daichi Suzuki, Kuniyasu Niizuma, Makoto Ohta, Teiji Tominaga

    Tenth International Conference on Flow Dynamics Proceedings 592-593 2013/11

  192. Relative Residence Time Prolongation in Intracranial Aneurysms: A Possible Association With Atherosclerosis Peer-reviewed

    Shin-ichiro Sugiyama, Kuniyasu Niizuma, Toshio Nakayama, Hiroaki Shimizu, Hidenori Endo, Takashi Inoue, Miki Fujimura, Makoto Ohta, Akira Takahashi, Teiji Tominaga

    NEUROSURGERY 73 (5) 767-776 2013/11

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1227/NEU.0000000000000096  

    ISSN:0148-396X

    eISSN:1524-4040

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    BACKGROUND: Intracranial aneurysms can have atherosclerotic wall properties that may be important in predicting aneurysm history or estimating the potential risks of surgical treatments. OBJECTIVE: To investigate hemodynamic characteristics of atherosclerotic lesions in intracranial aneurysms using computational fluid dynamics. METHODS: Intraoperative video recordings of 30 consecutive patients with an unruptured middle cerebral artery aneurysm were examined to identify atherosclerotic lesions on an aneurysm wall. For computational fluid dynamics analyses, geometries of aneurysms and adjacent arteries were reconstructed from 3-dimensional rotational angiography. Transient simulations were conducted under patient-specific pulsatile inlet conditions measured by phase-contrast magnetic resonance velocimetry. Three hemodynamic wall parameters were calculated: time-averaged wall shear stress, oscillatory shear index, and relative residence time (RRT). Statistical analyses were performed to discriminate the risk factors of atherosclerotic lesion formation. RESULTS: Among 30 aneurysms, 7 atherosclerotic lesions with remarkable yellow lipid deposition were identified in 5 aneurysms. All 7 atherosclerotic lesions spatially agreed with the area with prolonged RRT. Univariate analysis revealed that male sex (P = .03), cigarette smoking (P = .047), and maximum RRT (P = .02) are significantly related to atherosclerotic lesion on the intracranial aneurysmal wall. Of those variables that influenced atherosclerotic lesion of the intracranial aneurysmal wall, male sex (P = .005) and maximum RRT (P = .004) remained significant in the multivariate regression model. CONCLUSION: The area with prolonged RRT colocalized with atherosclerotic change on the aneurysm wall. Male sex and maximum RRT were independent risk factors for atherogenesis in intracranial aneurysms.

  193. ガンマナイフ治療で経過良好であったeloquent areaの脳動静脈奇形の1例

    増山 祥二, 新妻 邦泰, 鈴木 保宏, 園部 真也, 鹿毛 敦志, 府川 修

    磐城共立病院医報 34 (1) 36-43 2013/09

  194. 経頭蓋刺激運動誘発電位の刺激閾値の術中変動に関する検討

    阿部 誠, 佐々木 達也, 昆 博之, 斎藤 敦志, 菊池 登志雄, 新妻 邦泰, 西嶌 美知春

    青森県立中央病院医誌 58 (3) 84-88 2013/09

  195. An operated case of a meningioma causing acute subdural hematoma Peer-reviewed

    Masashi Chonan, Kuniyasu Niizuma, Shinya Koyama, Hiroyuki Kon, Seiya Sannohe, Hidekachi Kurotaki, Hiroshi Midorikawa, Tatsuya Sasaki, Michiharu Nishijima

    Neurological Surgery 41 (3) 235-239 2013/03

    ISSN:0301-2603 1882-1251

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    We report a rare case of a meningioma causing acute hematoma A 67-year-old woman presented with sudden headache No evidence of trauma was seen. CT demonstrated a subdural hematoma in the convexity of the fronto-temporal lobe Magnetic resonance imaging showed marked signal heterogeneity in the convexity of the frontal lobe One week later, the patient underwent hematoma evacuation and tumor resection including the attached dura mater. The histological diagnosis was meningothelial meningioma The clot was connected directly to the tumor and the origin of the subdural hematoma was identified as the meningioma. Postoperative course was uneventful, and the headache improved Meningiomas have a relatively benign course but rarely present with hemorrhage Surgical exploration is the effective and recommended treatment.

  196. Concurrent dural and perimedullary arteriovenous fistulas at the craniocervical junction: Case series with special reference to angioarchitecture ; Clinical article Peer-reviewed

    Kenichi Sato, Toshiki Endo, Kuniyasu Niizuma, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Teiji Tominaga

    Journal of Neurosurgery 118 (2) 451-459 2013/02

    DOI: 10.3171/2012.10.JNS121028  

    ISSN:0022-3085 1933-0693

    eISSN:1933-0693

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    Object. Dural arteriovenous fistulas (DAVFs) and perimedullary arteriovenous fistulas (PAVFs) are uncommonly associated in the craniocervical junction. The purpose of this study was to describe the clinical and angiographic characteristics of such concurrent lesions. Methods. Authors reviewed 9 cases with a coexistent DAVF and PAVF at the craniocervical junction. Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were assessed. Results. All patients (male/female ratio 5:4 mean age 66.3 years) presented with subarachnoid hemorrhage. Angiography revealed that 8 patients had both a DAVF and PAVF on the same side, whereas 1 patient had 3 arteriovenous fistulas, 1 DAVF, and 1 PAVF on the right side and 1 DAVF on the left side. All of the fistulas shared dilated perimedullary veins (anterior spinal vein, 7 cases anterolateral spinal vein, 2 cases) as a main drainage route. The shared drainage route was rostrally directed in 8 of 9 cases. Eight patients exhibited an arterial aneurysm on the distal side of the feeding arteries to the PAVF, and the aneurysm in each case was intraoperatively confirmed as a bleeding point. One patient had ruptured venous ectasia at the perimedullary fistulous point. All patients underwent direct surgery via a posterolateral approach. No recurrence was observed in the 4 patients who underwent postoperative angiography, and no rebleeding event was recorded among any of the 9 patients during the follow-up period (mean 38.4 months). Conclusions. The similarity of the angioarchitecture and the close anatomical relationship between DAVF and PAVF at the craniocervical junction suggested that these lesions are pathogenetically linked. The pathophysiological mechanism and anatomical features of these lesions represent a unique vascular anomaly that should be recognized angiographically to plan a therapeutic strategy. © AANS, 2013.

  197. 高齢者の症候性脳血管攣縮 非高齢者との比較 Peer-reviewed

    井上 瑞穂, 高沢 弘樹, 大谷 啓介, 長南 雅志, 新妻 邦泰, 小山 新弥, 昆 博之, 緑川 宏, 佐々木 達也, 西嶌 美知春

    脳血管攣縮 28 42-45 2013/02

  198. Pulsed-liquid jet surgical device: Evolution from shock/bubble interaction to clinical application Peer-reviewed

    Nakagawa A, Ohtani K, Ogawa Y, Endo T, Iwasaki M, Niizuma K, Arafune T, Washio T, Kato T, Kudo D, Nakanishi C, Sakurai T, Kamiyama Y, Sato C, Yamada M, Nakano T, Yamashita S, Suzuki T, Tanaka Y, Hagiwara Y, Kunikata H, Kawamoto S, Tominaga T

    Proceedings of the Tenth International Conference on Flow Dynamics 568-569 2013

  199. Guidelines for the management of traumatic vascular disorders in head and neck - Pathogenesis, diagnosis and treatment - Peer-reviewed

    TATSUYA SASAKI, MASASHI CHONAN, KUNIYASU NIIZUMA, SHINYA KOYAMA, ATSUSHI SAITO, HIROYUKI KON, MICHIHARU NISHIJIMA, AKIRA SATOH

    Neurotraumatology 35 (2) 87-94 2012/12/30

  200. 経過観察中に破裂した未破裂脳動脈瘤の検討 Peer-reviewed

    小山 新弥, 眞野 唯, 長南 雅志, 新妻 邦泰, 昆 博之, 佐々木 達也, 西嶌 美知春

    東北脳血管障害研究会学術集会記録集 34回 153-166 2012/12

  201. 抗凝固療法中の慢性硬膜下血腫患者における塞栓・出血リスクスコアの検討 Peer-reviewed

    齊藤 元太, 佐々木 達也, 長南 雅志, 新妻 邦泰, 小山 新弥, 昆 博之, 西嶌 美知春

    Neurotraumatology 35 (2) 141-146 2012/12

  202. Childhood transverse sinus dural arteriovenous fistula treated with endovascular and direct surgery: A case report Peer-reviewed

    Kuniyasu Niizuma, Hiroyuki Sakata, Shinya Koyama, Hiroyuki Kon, Masashi Chonan, Tatsuya Sasaki, Michiharu Nishijima, Masayuki Ezura, Teiji Tominaga

    Neurological Surgery 40 (11) 1015-1020 2012/11

    ISSN:0301-2603 1882-1251

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    Infantile dural arteriovenous fistula is a rare cerebrovascular malformation carrying a poor prognosis with an anatomic cure of only 9%. Endovascular embolization is mainly selected to treat this entity, aiming to obtain normal development of the patients. We present a case of a 20-month-old girl with epilepsy. Digital subtraction angiography revealed a dural arteriovenous fistula involving the right transverse sinus. The artenovenous fistula was fed by multiple dural branches from the middle meningeal, occipital, meningohypophyseal. and anteroinferior cerebellar arteries. The right transverse sinus was transvenously embolized with platinum coils. Although the shunt flow remained, the patient was liberated from epilepsy. Nine months later, the patient suffered from a recurrence of epilepsy. Digital subtraction angiography demonstrated some increase in shunt flow. Right middle meningeal, occipital, posterior deep temporal, and tentorial arteries were transarterially embolized using N-butyl cyanoacrylate, followed by complete surgical resection of the nght transverse sinus. The shunt flow disappeared after surgery, and her epilepsy improved significantly. Our experience suggests that the combination of endovascular and surgical treatment is effective for recurrent infantile dural arteriovenous fistula.

  203. Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice Peer-reviewed

    Hiroyuki Sakata, Purnima Narasimhan, Kuniyasu Niizuma, Carolina M. Maier, Takuma Wakai, Pak H. Chan

    BRAIN 135 (11) 3298-3310 2012/11

    Publisher: OXFORD UNIV PRESS

    DOI: 10.1093/brain/aws259  

    ISSN:0006-8950

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    Transplantation of neural stem cells provides a promising therapy for stroke. Its efficacy, however, might be limited because of massive grafted-cell death after transplantation, and its insufficient capability for tissue repair. Interleukin 6 is a pro-inflammatory cytokine involved in the pathogenesis of various neurological disorders. Paradoxically, interleukin 6 promotes a pro-survival signalling pathway through activation of signal transducer and activator of transcription 3. In this study, we investigated whether cellular reprogramming of neural stem cells with interleukin 6 facilitates the effectiveness of cell transplantation therapy in ischaemic stroke. Neural stem cells harvested from the subventricular zone of foetal mice were preconditioned with interleukin 6 in vitro and transplanted into mouse brains 6 h or 7 days after transient middle cerebral artery occlusion. Interleukin 6 preconditioning protected the grafted neural stem cells from ischaemic reperfusion injury through signal transducer and activator of transcription 3-mediated upregulation of manganese superoxide dismutase, a primary mitochondrial antioxidant enzyme. In addition, interleukin 6 preconditioning induced secretion of vascular endothelial growth factor from the neural stem cells through activation of signal transducer and activator of transcription 3, resulting in promotion of angiogenesis in the ischaemic brain. Furthermore, transplantation of interleukin 6-preconditioned neural stem cells significantly attenuated infarct size and improved neurological performance compared with non-preconditioned neural stem cells. This interleukin 6-induced amelioration of ischaemic insults was abolished by transfecting the neural stem cells with signal transducer and activator of transcription 3 small interfering RNA before transplantation. These results indicate that preconditioning with interleukin 6, which reprograms neural stem cells to tolerate oxidative stress after ischaemic reperfusion injury and to induce angiogenesis through activation of signal transducer and activator of transcription 3, is a simple and beneficial approach for enhancing the effectiveness of cell transplantation therapy in ischaemic stroke.

  204. Neural Stem Cells Genetically Modified to Overexpress Cu/Zn-Superoxide Dismutase Enhance Amelioration of Ischemic Stroke in Mice Peer-reviewed

    Hiroyuki Sakata, Kuniyasu Niizuma, Takuma Wakai, Purnima Narasimhan, Carolina M. Maier, Pak H. Chan

    STROKE 43 (9) 2423-+ 2012/09

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1161/STROKEAHA.112.656900  

    ISSN:0039-2499

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    Background and Purpose-The harsh host brain microenvironment caused by production of reactive oxygen species after ischemic reperfusion injury offers a significant challenge to survival of transplanted neural stem cells (NSCs) after ischemic stroke. Copper/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We have investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted stem cells and accelerates amelioration of ischemic stroke. Methods-NSCs genetically modified to overexpress or downexpress SOD1 were administered intracerebrally 2 days after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from Days 0 to 28 after stroke. Results-Overexpression of SOD1 suppressed production of superoxide anions after ischemic reperfusion injury and reduced NSC death after transplantation. In contrast, downexpression of SOD1 promoted superoxide generation and increased oxidative stress-mediated NSC death. Transplantation of SOD1-overexpressing NSCs enhanced angiogenesis in the ischemic border zone through upregulation of vascular endothelial growth factor. Moreover, grafted SOD1-overexpressing NSCs reduced infarct size and improved behavioral performance compared with NSCs that were not genetically modified. Conclusions-Our findings reveal a strong involvement of SOD1 expression in NSC survival after ischemic reperfusion injury. We propose that conferring antioxidant properties on NSCs by genetic manipulation of SOD1 is a potential approach for enhancing the effectiveness of cell transplantation therapy in ischemic stroke. (Stroke. 2012;43:2423-2429.)

  205. 動脈瘤を形成せず、侵襲性アスペルギルス血管炎の破綻によりくも膜下出血を呈した1剖検例

    三木 康生, 冨山 誠彦, 今 智矢, 羽賀 理恵, 西嶌 春生, 鈴木 千恵子, 馬場 正之, 緑川 宏, 大谷 啓介, 長南 雅志, 新妻 邦泰, 小山 新弥, 昆 博之, 佐々木 達也, 西嶌 美知春, 三戸 聖也, 黒滝 日出一, 若林 孝一

    青森県立中央病院医誌 57 (3) 126-127 2012/09

    Publisher: None

    ISSN:0387-0138

  206. Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats Peer-reviewed

    Hiroyuki Sakata, Kuniyasu Niizuma, Hideyuki Yoshioka, Gab Seok Kim, Joo Eun Jung, Masataka Katsu, Purnima Narasimhan, Carolina M. Maier, Yasuhiro Nishiyama, Pak H. Chan

    JOURNAL OF NEUROSCIENCE 32 (10) 3462-3473 2012/03

    Publisher: SOC NEUROSCIENCE

    DOI: 10.1523/JNEUROSCI.5686-11.2012  

    ISSN:0270-6474

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    Transplantation of neural stem cells (NSCs) offers a novel therapeutic strategy for stroke; however, massive grafted cell death following transplantation, possibly due to a hostile host brain environment, lessens the effectiveness of this approach. Here, we have investigated whether reprogramming NSCs with minocycline, a broadly used antibiotic also known to possess cytoprotective properties, enhances survival of grafted cells and promotes neuroprotection in ischemic stroke. NSCs harvested from the subventricular zone of fetal rats were preconditioned with minocycline in vitro and transplanted into rat brains 6 h after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from days 0-28 after stroke. For in vitro experiments, NSCs were subjected to oxygen-glucose deprivation and reoxygenation. Cell viability and antioxidant gene expression were analyzed. Minocycline preconditioning protected the grafted NSCs from ischemic reperfusion injury via upregulation of Nrf2 and Nrf2-regulated antioxidant genes. Additionally, preconditioning with minocycline induced the NSCs to release paracrine factors, including brain-derived neurotrophic factor, nerve growth factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor. Moreover, transplantation of the minocycline-preconditioned NSCs significantly attenuated infarct size and improved neurological performance, compared with non-preconditioned NSCs. Minocycline-induced neuroprotection was abolished by transfecting the NSCs with Nrf2-small interfering RNA before transplantation. Thus, preconditioning with minocycline, which reprograms NSCs to tolerate oxidative stress after ischemic reperfusion injury and express higher levels of paracrine factors through Nrf2 up-regulation, is a simple and safe approach to enhance the effectiveness of transplantation therapy in ischemic stroke.

  207. 中枢神経系原発悪性リンパ腫のステロイド反応性に関する検討

    眞野 唯, 金森 政之, 井上 瑞穂, 新妻 邦泰, 成澤 あゆみ, 小山 新弥, 昆 博之, 久保 恒明, 黒滝 日出一, 佐々木 達也, 西嶌 美知春

    青森県立中央病院医誌 56 (4) 141-147 2011/12

  208. 放射線治療で28年間経過観察を行った斜台部髄膜腫の1例

    増山 祥二, 鈴木 保宏, 新妻 邦泰, 伊藤 明, 浅野 重之

    磐城共立病院医報 32 (1) 46-51 2011/11

  209. Consistent Injury to Medium Spiny Neurons and White Matter in the Mouse Striatum after Prolonged Transient Global Cerebral Ischemia Peer-reviewed

    Hideyuki Yoshioka, Kuniyasu Niizuma, Masataka Katsu, Hiroyuki Sakata, Nobuya Okami, Pak H. Chan

    JOURNAL OF NEUROTRAUMA 28 (4) 649-660 2011/04

    Publisher: MARY ANN LIEBERT INC

    DOI: 10.1089/neu.2010.1662  

    ISSN:0897-7151

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    A reproducible transient global cerebral ischemia (tGCI) mouse model has not been fully established. Although striatal neurons and white matter are recognized to be vulnerable to ischemia, their injury after tGCI in mice has not been elucidated. The purpose of this study was to evaluate injuries to striatal neurons and white matter after tGCI in C57BL/6 mice, and to develop a reproducible tGCI model. Male C57BL/6 mice were subjected to tGCI by bilateral common carotid artery occlusion (BCCAO). Mice whose cortical cerebral blood flow after BCCAO decreased to less than 13% of the pre-ischemic value were used. Histological analysis showed that at 3 days after 22 min of BCCAO, striatal neurons were injured more consistently than those in other brain regions. Quantitative analysis of cytochrome c release into the cytosol and DNA fragmentation in the striatum showed consistent injury to the striatum. Immunohistochemistry and Western blot analysis revealed that DARPP-32-positive medium spiny neurons, the majority of striatal neurons, were the most vulnerable among the striatal neuronal subpopulations. The striatum (especially medium spiny neurons) was susceptible to oxidative stress after tGCI, which is probably one of the mechanisms of vulnerability. SMI-32 immunostaining showed that white matter in the striatum was also consistently injured 3 days after 22 min of BCCAO. We thus suggest that this is a tGCI model using C57BL/6 mice that consistently produces neuronal and white matter injury in the striatum by a simple technique. This model can be highly applicable for elucidating molecular mechanisms in the brain after global ischemia.

  210. Hemosiderin Detected by T-2*-Weighted Magnetic Resonance Imaging in Patients With Unruptured Cerebral Aneurysms: Indication of Previous Bleeding? Peer-reviewed

    Shihomi Takada, Takashi Inoue, Kuniyasu Niizuma, Hiroaki Shimizu, Teiji Tominaga

    NEUROLOGIA MEDICO-CHIRURGICA 51 (4) 275-281 2011/04

    Publisher: JAPAN NEUROSURGICAL SOC

    DOI: 10.2176/nmc.51.275  

    ISSN:0470-8105

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    Previous bleeding from a cerebral aneurysm indicates a higher risk of rupture. Hemosiderin may be detected during aneurysm surgery or by preoperative imaging sensitive to hemosiderin. The detection of hemosiderin deposits by T-2*-weighted magnetic resonance (MR) imaging was evaluated in 49 patients with unruptured cerebral aneurysms who underwent open surgery. MR imaging was performed using 3.0 tesla MR scanner. Two sequences of T-2*-weighted imaging, and proton density images were obtained. Preliminary study in patients with old subarachnoid hemorrhage provided the definitions of likely pathological findings during surgery and on T-2*-weighted imaging due to previous hemorrhage. Hemosiderin deposits in the subarachnoid space were observed during surgery in 9 of the 49 patients, although no obvious rupture site was detected around the aneurysm wall. Size, presence of bleb, location, and number of aneurysms showed no significant difference between patients with and without hemosiderin deposition. Hypointense areas on T-2*-weighted imaging were recognized in four patients. The mean size of the aneurysms in these patients was 9.8 mm, significantly larger than those in other patients (p = 0.029). Hemosiderin deposits were observed during surgery in sites close to the lesions on T-2*-weighted imaging in two of these four patients. Hemosiderin deposits are not rare in patients with unruptured aneurysms, and preoperative T-2*-weighted imaging can detect such deposits.

  211. NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia Peer-reviewed

    Hideyuki Yoshioka, Kuniyasu Niizuma, Masataka Katsu, Nobuya Okami, Hiroyuki Sakata, Gab Seok Kim, Purnima Narasimhan, Pak H. Chan

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 31 (3) 868-880 2011/03

    Publisher: NATURE PUBLISHING GROUP

    DOI: 10.1038/jcbfm.2010.166  

    ISSN:0271-678X

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    Medium spiny neurons (MSNs) constitute most of the striatal neurons and are known to be vulnerable to ischemia; however, the mechanisms of the vulnerability remain unclear. Activated forms of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase (NOX), which require interaction between cytosolic and membrane-bound subunits, are among the major sources of superoxide in the central nervous system. Although increasing evidence suggests that NOX has important roles in neurodegenerative diseases, its roles in MSN injury after transient global cerebral ischemia (tGCI) have not been elucidated. To clarify this issue, C57BL/6 mice were subjected to tGCI by bilateral common carotid artery occlusion for 22 minutes. Western blot analysis revealed upregulation of NOX subunits and recruitment of cytosolic subunits to the cell membrane at early (3 to 6 hours) and late (72 hours) phases after tGCI. Taken together with immunofluorescent studies, this activation arose in MSNs and endothelial cells at the early phase, and in reactive microglia at the late phase. Pharmacological and genetic inhibition of NOX attenuated oxidative injury, microglial activation, and MSN death after tGCI. These findings suggest that NOX has pivotal roles in MSN injury after tGCI and could be a therapeutic target for brain ischemia. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 868-880; doi:10.1038/jcbfm.2010.166; published online 22 September 2010

  212. Transplanted Stem Cell-Secreted Vascular Endothelial Growth Factor Effects Poststroke Recovery, Inflammation, and Vascular Repair Peer-reviewed

    Nobutaka Horie, Marta P. Pereira, Kuniyasu Niizuma, Guohua Sun, Hadar Keren-Gill, Angelo Encarnacion, Mehrdad Shamloo, Scott A. Hamilton, Kewen Jiang, Stephen Huhn, Theo D. Palmer, Tonya M. Bliss, Gary K. Steinberg

    STEM CELLS 29 (2) 274-285 2011/02

    Publisher: WILEY-BLACKWELL

    DOI: 10.1002/stem.584  

    ISSN:1066-5099

    eISSN:1549-4918

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    Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after subacute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human vascular endothelial growth factor (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier integrity and suppression of inflammation was followed by a delayed spatiotemporal regulated increase in neovascularization. These events coincided with a bimodal pattern of functional recovery, with, an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multimodal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. STEM CELLS 2011;29:274-285

  213. 各種画像の三次元融合画像を用いた術前検討の有用性 Peer-reviewed

    新妻 邦泰, 井上 敬, 藤村 幹, 藤原 悟, 清水 宏明, 冨永 悌二

    東北脳血管障害研究会学術集会記録集 32回 11-15 2010/12

    ISSN:1880-9278

  214. Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood-brain barrier dysfunction in vivo Peer-reviewed

    Masataka Katsu, Kuniyasu Niizuma, Hideyuki Yoshioka, Nobuya Okami, Hiroyuki Sakata, Pak H. Chan

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 30 (12) 1939-1950 2010/12

    Publisher: NATURE PUBLISHING GROUP

    DOI: 10.1038/jcbfm.2010.45  

    ISSN:0271-678X

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    Hemoglobin (Hb) released from extravasated erythrocytes is implicated in brain edema after intracerebral hemorrhage (ICH). Hemoglobin is a major component of blood and a potent mediator of oxidative stress after ICH. Oxidative stress and matrix metalloproteinases (MMPs) are associated with blood-brain barrier (BBB) dysfunction. This study was designed to elucidate whether Hb-induced oxidative stress contributes to MMP-9 activation and BBB dysfunction in vivo. An intracerebral injection of Hb into rat striata induced increased hydroethidine (HEt) signals in parallel with MMP-9 levels. In situ gelatinolytic activity colocalized with oxidized HEt signals in vessel walls, accompanied by immunoglobulin G leakage and a decrease in immunoactivity of endothelial barrier antigen, a marker of endothelial integrity. Administration of a nonselective MMP inhibitor prevented MMP-9 levels and albumin leakage in injured striata. Moreover, reduction in oxidative stress by copper/zinc-superoxide dismutase (SOD1) overexpression reduced oxidative stress, MMP-9 levels, albumin leakage, and subsequent apoptosis compared with wild-type littermates. We speculate that Hb-induced oxidative stress may contribute to early BBB dysfunction and subsequent apoptosis, partly through MMP activation, and that SOD1 overexpression may reduce Hb-induced oxidative stress, BBB dysfunction, and apoptotic cell death. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1939-1950; doi:10.1038/jcbfm.2010.45; published online 31 March 2010

  215. Efficacy of Revascularization Surgery for Moyamoya Syndrome Associated With Graves&apos; Disease Peer-reviewed

    Hidenori Endo, Miki Fujimura, Kuniyasu Niizuma, Hiroaki Shimizu, Teiji Tominaga

    NEUROLOGIA MEDICO-CHIRURGICA 50 (11) 977-983 2010/11

    Publisher: JAPAN NEUROSURGICAL SOC

    DOI: 10.2176/nmc.50.977  

    ISSN:0470-8105

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    Appropriate management of moyamoya syndrome associated with Graves&apos; disease is undetermined because of the rarity of this combination Patients tend to present with cerebrovascular events such as transient ischemic attack (TIA) in a thyrotoxic state, which is relieved by proper antithyroid therapy Four patients with moyamoya syndrome associated with Graves&apos; disease were successfully treated with revascularization surgery on 5 hemispheres among 58 consecutive patients (2-62 years old, mean 34 4 years) with moyamoya disease in 80 hemispheres treated from March 2004 to May 2007 Three patients presented with TIA, and one patient presented with intracerebral hemorrhage Three patients were thyrotoxic at the onset of the cerebrovascular events All patients underwent revascularization surgery after normalization of thyroid function Euthyroid state was strictly maintained perioperatively One patient developed symptomatic cerebral hyperperfusion, which was resolved by blood pressure control Postoperative courses of the other patients were uneventful, and all 4 patients have remained neurologically stable after discharge Cerebrovascular reconstruction surgery is a successful treatment option for moyamoya syndrome associated with Graves&apos; disease Timing of surgery during the euthyroid state and perioperative management considering the thyroid function and the cerebral hemodynamic change are the keys to successful surgical treatment

  216. Reperfusion and Neurovascular Dysfunction in Stroke: from Basic Mechanisms to Potential Strategies for Neuroprotection Peer-reviewed

    Joo Eun Jung, Gab Seok Kim, Hai Chen, Carolina M. Maier, Purnima Narasimhan, Yun Seon Song, Kuniyasu Niizuma, Masataka Katsu, Nobuya Okami, Hideyuki Yoshioka, Hiroyuki Sakata, Christina E. Goeders, Pak H. Chan

    MOLECULAR NEUROBIOLOGY 41 (2-3) 172-179 2010/06

    Publisher: HUMANA PRESS INC

    DOI: 10.1007/s12035-010-8102-z  

    ISSN:0893-7648

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    Effective stroke therapies require recanalization of occluded cerebral blood vessels. However, reperfusion can cause neurovascular injury, leading to cerebral edema, brain hemorrhage, and neuronal death by apoptosis/necrosis. These complications, which result from excess production of reactive oxygen species in mitochondria, significantly limit the benefits of stroke therapies. We have developed a focal stroke model using mice deficient in mitochondrial manganese-superoxide dismutase (SOD2-/+) to investigate neurovascular endothelial damage that occurs during reperfusion. Following focal stroke and reperfusion, SOD2-/+ mice had delayed blood-brain barrier breakdown, associated with activation of matrix metalloproteinase and high brain hemorrhage rates, whereas a decrease in apoptosis and hemorrhage was observed in SOD2 overexpressors. Thus, induction and activation of SOD2 is a novel strategy for neurovascular protection after ischemia/reperfusion. Our recent study identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse SOD2 gene. During reperfusion, activation of STAT3 and its recruitment into the SOD2 gene were blocked, resulting in increased oxidative stress and neuronal apoptosis. In contrast, pharmacological activation of STAT3 induced SOD2 expression, which limits ischemic neuronal death. Our studies point to antioxidant-based neurovascular protective strategies as potential treatments to expand the therapeutic window of currently approved therapies.

  217. 松果体及び鞍上部に腫瘍を有しない多発性頭蓋内胚腫の一例

    新妻邦泰, 隈部俊宏, 斎藤竜太, 園田順彦, 渡辺みか, 冨永悌二

    Brain Tumor Pathology 28 (Suppl.) 113-113 2010/05

  218. 無症候性脳動脈瘤症例におけるT2*強調画像低信号領域の臨床的意義 Peer-reviewed

    高田 志保美, 井上 敬, 新妻 邦泰, 清水 宏明, 冨永 悌二

    東北脳血管障害研究会学術集会記録集 31回 43-50 2009/12

    ISSN:1880-9278

  219. CK2 Is a Novel Negative Regulator of NADPH Oxidase and a Neuroprotectant in Mice after Cerebral Ischemia Peer-reviewed

    Gab Seok Kim, Joo Eun Jung, Kuniyasu Niizuma, Pak H. Chan

    JOURNAL OF NEUROSCIENCE 29 (47) 14779-14789 2009/11

    Publisher: SOC NEUROSCIENCE

    DOI: 10.1523/JNEUROSCI.4161-09.2009  

    ISSN:0270-6474

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    NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. In this study, we identified casein kinase 2 (CK2) as a critical modulator of NADPH oxidase and elucidated the role of CK2 as a neuroprotectant after oxidative insults to the brain. We found that the protein levels of the catalytic subunits CK2 alpha and CK2 alpha&apos;, as well as the total activity of CK2, are significantly reduced after transient focal cerebral ischemia (tFCI). We also found this deactivation of CK2 caused by ischemia/reperfusion increases expression of Nox2 and translocation of p67(phox) and Rac1 to the membrane after tFCI. Interestingly, we found that the inactive status of Rac1 was captured by the catalytic subunit CK2 alpha under normal conditions. However, binding between CK2 alpha and Rac1 was immediately diminished after tFCI, and Rac1 activity was markedly increased after CK2 inhibition. Moreover, we found that deactivation of CK2 in the mouse brain enhances production of ROSs and neuronal cell death via increased NADPH oxidase activity. The increased brain infarct volume caused by CK2 inhibition was restored by apocynin, a NADPH oxidase inhibitor. This study suggests that CK2 can be a direct molecular target for modulation of NADPH oxidase activity after ischemic brain injury.

  220. Potential Role of PUMA in Delayed Death of Hippocampal CA1 Neurons After Transient Global Cerebral Ischemia Peer-reviewed

    Kuniyasu Niizuma, Hidenori Endo, Chikako Nito, D. Jeannie Myer, Pak H. Chan

    STROKE 40 (2) 618-625 2009/02

    Publisher: LIPPINCOTT WILLIAMS & WILKINS

    DOI: 10.1161/STROKEAHA.108.524447  

    ISSN:0039-2499

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    Background and Purpose-p53-upregulated modulator of apoptosis (PUMA), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and-independent forms of apoptosis. PUMA localizes to mitochondria and interacts with antiapoptotic Bcl-2 and Bcl-X(L) or proapoptotic Bax in response to death stimuli. Although studies have shown that PUMA is associated with pathomechanisms of cerebral ischemia, clearly defined roles for PUMA in ischemic neuronal death remain unclear. The purpose of this study was to determine potential roles for PUMA in cerebral ischemia. Methods-Five minutes of transient global cerebral ischemia (tGCI) were induced by bilateral common carotid artery occlusion combined with hypotension. Results-PUMA was upregulated in vulnerable hippocampal CA1 neurons after tGCI as shown by immunohistochemistry. In Western blot and coimmunoprecipitation analyses, PUMA localized to mitochondria and was bound to Bcl-XL and Bax in the hippocampal CA1 subregion after tGCI. PUMA upregulation was inhibited by pifithrin-alpha, a specific inhibitor of p53, suggesting that PUMA is partly controlled by the p53 transcriptional pathway after tGCI. Furthermore, reduction in oxidative stress by overexpression of copper/zinc superoxide dismutase, which is known to be protective of vulnerable ischemic hippocampal neurons, inhibited PUMA upregulation and subsequent hippocampal CA1 neuronal death after tGCI. Conclusions-These results imply a potential role for PUMA in delayed CA1 neuronal death after tGCI and that it could be a molecular target for therapy. (Stroke. 2009;40:618-625.)

  221. Transient global cerebral ischemia model in mice Peer-reviewed

    Kuniyasu Niizuma, Hidenori Endo, Chikako Nito, D. Jeannie Myer, Gab Seok Kim, Teiji Tominaga, Pak H. Chan

    Animal Models of Acute Neurological Injuries 115-125 2009

    Publisher: Humana Press

    DOI: 10.1007/978-1-60327-185-1_10  

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    The transient global ischemia model is used to analyze selective neuronal death in vulnerable regions including the CA1 subregion of the hippocampus and in certain cortical neurons. In this mouse global ischemia model, bilateral common carotid arteries are reversibly occluded, and the individual anatomical backgrounds are normalized by evaluating the patency of the posterior communicating artery. Using this evaluation, this model might be used for mouse strains with various genetic backgrounds. © 2009 Humana Press.

  222. Middle cerebral artery plaque imaging using 3-Tesla high-resolution MRI Peer-reviewed

    Kuniyasu Niizuma, Hiroaki Shimizu, Shihomi Takada, Teiji Tominaga

    JOURNAL OF CLINICAL NEUROSCIENCE 15 (10) 1137-1141 2008/10

    Publisher: CHURCHILL LIVINGSTONE

    DOI: 10.1016/j.jocn.2007.09.024  

    ISSN:0967-5868

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    Diagnosis of deep subcortical infarcts based on atherosclerosis of the middle cerebral artery (MCA) is important because this type of infarct is usually more aggressive than typical lacunar infarcts. However. current imaging techniques are of limited utility in the diagnosis of MCA plaques. Here, we report the use of 3-Tesla (3T) high-resolution moderate T-weighted imaging (HRT2WI) to detect MCA plaques in three patients with acute MCA perforator territory infarcts. MCA plaques were seen with HRT2WI in a patient with MCA stenosis, which was observed by magnetic resonance angiography (M RA). OF the two patients Without MCA stenosis (also confirmed by MRA), one had thin MCA plaques and the other had normal walls based on HRT2WI. Progression of symptoms occurred ill the patients with plaques. We conclude that 3T HRT2WI call identify plaque On MCA walls and has the potential to identify patients at risk for stroke progression or recurrence. (c) 2007 Elsevier Ltd. All rights reserved.

  223. Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A(2) signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion Peer-reviewed

    Chikako Nito, Hiroshi Kamada, Hidenori Endo, Kuniyasu Niizuma, D. Jeannie Myer, Pak H. Chan

    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 28 (10) 1686-1696 2008/10

    Publisher: NATURE PUBLISHING GROUP

    DOI: 10.1038/jcbfm.2008.60  

    ISSN:0271-678X

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    Cytosolic phospholipase A(2) (cPLA(2)) is a key enzyme that mediates arachidonic acid metabolism, which causes cerebral ischemia-induced oxidative injury, blood-brain barrier (BBB) dysfunction, and edema. Recent reports have shown that p38 mitogen-activated protein kinase (MAPK) is related to phosphorylation and activation of cPLA(2) and release of arachidonic acid. However, involvement of the p38 MAPK pathway in cPLA(2) activation and of reactive oxygen species in expression of p38 MAPK/cPLA(2) after ischemia-reperfusion injury in the brain remains unclear. To address these issues, we used a model of transient focal cerebral ischemia (tFCI) in rats. Western blot analysis showed a significant increase in expression of phospho-p38 MAPK and phospho-cPLA(2) in rat brain cortex after tFCI. Activity assays showed that both p38 MAPK and cPLA2 activation markedly increased 1 day after reperfusion. Intraventricular administration of SB203580 significantly suppressed activation and phosphorylation of cPLA(2) and attenuated BBB extravasation and subsequent edema. Moreover, overexpression of copper/zinc-superoxide dismutase remarkably diminished activation and phosphorylation of both p38 MAPK and cPLA(2) after reperfusion. These findings suggest that the p38 MAPK/cPLA(2) pathway may promote BBB disruption with secondary vasogenic edema and that superoxide anions can stimulate this pathway after ischemia-reperfusion injury.

  224. The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats Peer-reviewed

    Kuniyasu Niizuma, Hidenori Endo, Chikako Nito, D. Jeannie Myer, Gab Seok Kim, Pak H. Chan

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105 (42) 16368-16373 2008/10

    Publisher: NATL ACAD SCIENCES

    DOI: 10.1073/pnas.0806222105  

    ISSN:0027-8424

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    A brief period of global brain ischemia, such as that induced by cardiac arrest or cardiopulmonary bypass surgery, causes cell death in vulnerable hippocampal CA1 pyramidal neurons days after reperfusion. Although numerous factors have been suggested to account for this phenomenon, the mechanisms underlying it are poorly understood. We describe a cell death signal called the PIDDosome, a protein complex of p53-induced protein with a death domain (PIDD), receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (RAIDD), and procaspase-2. We induced 5 min of transient global cerebral ischemia (tGCI) using bilateral common carotid artery occlusion with hypotension. Western blot analysis showed that expression of twice-cleaved fragment of PIDD (PIDD-CC) increased in the cytosolic fraction of the hippocampal CA1 subregion and preceded procaspase-2 activation after tGCI. Caspase-2 cleaved Bid in brain homogenates. Co-immunoprecipitation and immunofluorescent studies demonstrated that PIDD-CC, RAIDD, and procaspase-2 were co-localized and bound directly, which indicates the formation of the PIDD death domain complex. Furthermore, we tested inhibition of PIDD expression by using small interfering RNA (siRNA) treatment that was initiated 48 h before tGCI. Administration of siRNA against PIDD decreased not only expression of PIDD-CC, but also activation of procaspase-2 and Bid, resulting in a decrease in histological neuronal damage and DNA fragmentation in the hippocampal CA1 subregion after tGCI. These results imply that PIDD plays an important role in procaspase-2 activation and delayed CA1 neuronal death after tGCI. We propose that PIDD is a hypothetical molecular target for therapy against neuronal death after tGCI.

  225. Induction of MMP-9 expression and endothelial injury by oxidative stress after spinal cord injury Peer-reviewed

    Fengshan Yu, Hiroshi Kamada, Kuniyasu Niizuma, Hidenori Endo, Pak H. Chan

    JOURNAL OF NEUROTRAUMA 25 (3) 184-195 2008/03

    Publisher: MARY ANN LIEBERT INC

    DOI: 10.1089/neu.2007.0438  

    ISSN:0897-7151

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    Matrix metalloproteinase-9 (MMP-9) activation plays an important role in blood - brain barrier (BBB) dysfunction after central nervous system injury. Oxidative stress is also implicated in the pathogenesis after cerebral ischemia and spinal cord injury (SCI), but the relationship between MMP-9 activation and oxidative stress after SCI has not yet been clarified. We examined MMP-9 expression after SCI using copper/zinc - superoxide dismutase (SOD1) transgenic (Tg) rats. Our results show that MMP-9 activity significantly increased after SCI in both SOD1 Tg rats and their wild-type (Wt) littermates, although the increase was less in the SOD1 Tg rats. This pattern of MMP-9 expression was further confirmed by immunostaining and Western blot analysis. In situ zymography showed that gelatinolytic activity increased after SCI in the Wt rats, while the increase was less in the Tg rats. Evans blue extravasation increased in both the Wt and Tg rats, but was less in the SOD1 Tg rats. Inhibitor studies showed that, with an intrathecal injection of SB-3CT ( a selective MMP-2/MMP-9 inhibitor), the MMP activity, Evans blue extravasation, and apoptotic cell death decreased after SCI. We conclude that increased oxidative stress after SCI leads to MMP-9 upregulation, BBB disruption, and apoptosis, and that overexpression of SOD1 in Tg rats decreases oxidative stress and further attenuates MMP-9 mediated BBB disruption.

  226. Problems with Fiber Tracking in Visualizing the White Matter Tract Peer-reviewed

    Kuniyasu Niizuma, Toshihiro Kumabe, Hiroaki Shimizu, Shuichi Higano, Shoki Takahashi, Teiji Tominaga

    脳神経外科ジャーナル 16 (6) 504-509 2007/06

    DOI: 10.7887/jcns.16.504  

    ISSN:0917-950X

  227. Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome Peer-reviewed

    Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Tominaga Tominaga

    JOURNAL OF CLINICAL NEUROSCIENCE 14 (1) 53-55 2007/01

    Publisher: CHURCHILL LIVINGSTONE

    DOI: 10.1016/j.jocn.2005.09.021  

    ISSN:0967-5868

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    A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. The parasitic cysts and glioblastoma were microsurgically removed. Histological examination of surgical specimens revealed neurocysticercosis between the normal brain tissue and glioblastoma. The clinical course and histological findings suggest that the parasitic infection and/or genetic changes contributed to the malignant transformation of the astrocytic tumour. (C) 2006 Published by Elsevier Ltd.

  228. Surgical treatment of paraventricular cavernous angioma: Fibre tracking for visualizing the corticospinal tract and determining surgical approach Peer-reviewed

    Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Shuichi Higano, Teiji Tominaga

    JOURNAL OF CLINICAL NEUROSCIENCE 13 (10) 1028-1032 2006/12

    Publisher: CHURCHILL LIVINGSTONE

    DOI: 10.1016/j.jocn.2004.11.025  

    ISSN:0967-5868

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    Surgical treatment of deep-seated lesions involving the corticospinal tract is one of the most challenging areas of contemporary neurosurgery, even given the recent development of radiological methods including three-dimensional anisotropy contrast magnetic resonance imaging (MRI) axonography. Fibre tracking using diffusion tensor imaging is another MRI technique that can be used to visualize anisotropy and the orientation of white matter tracts in the brain. We report herein a patient with a paraventricular cavernous angioma manifesting as hemiparesis caused by haemorrhage. Preoperative conventional MRI failed to determine the anatomical relationship between the paraventricular lesion and the corticospinal tract, whereas fibre tracking using free software (dTV for MR-DTI analysis) indicated that the corticospinal tract was displaced anterolaterally from the medial side. The paraventricular lesion was completely removed without damaging the corticospinal tract using a transcortical transventricular approach. Preoperative fibre tracking is useful in surgical planning for procedures involving deep-seated lesions adjacent to the corticospinal tract, and may avoid postoperative morbidity due to corticospinal tract injury. (c) 2006 Elsevier Ltd. All rights reserved.

  229. Usefulness of regional cerebral oxygen saturation monitoring in balloon test occlusion Peer-reviewed

    Kuniyasu Niizuma, Hideyuki Kamii, Yasushi Matsumoto, Ryushi Kondoh, Hiroaki Shimizu, Teiji Tominaga

    NEUROLOGICAL SURGERY 34 (7) 695-702 2006/07

    Publisher: IGAKU-SHOIN LTD

    DOI: 10.11477/mf.1436100253  

    ISSN:0301-2603

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    Purpose Recently, temporary balloon test occlusion (BTO) of the internal carotid artery (IC) has become a well accepted procedure for preoperative evaluation of patients with IC large aneurysms. However, it might be dangerous to move patients fitted with a balloon catheter to the room for single-photon emission computed tomography (SPECT). We attempted to clarify the usefulness of regional cerebral oxygen saturation (rSO(2)) monitoring during BTO, comparing cerebral blood flow (CBF) obtained from SPECT. Materials and Methods Eight patients with an IC large aneurysm underwent BTO with rSO(2) monitoring. Regions of interest in the SPECT were defined in the area below the rSO2 sensor of each hemisphere. Correlations among rSO(2), CBF, stump pressure and appearance of symptoms were discussed. Results The rSO(2) significantly reduced during BTO (74.1 +/- 1.2 to 60.4 +/- 2.7%, p &lt; 0.001). The individual decreases in rSO(2) correlated with decreases of CBF from SPECT (r=0.966, P &lt; 0.001). Four patients with A rSO(2) (baseline rSO(2) - rSO(2) during IC occlusion) less than 12 points had no symptoms, but 4 patients with A rSO(2) more than 14 points had some symptoms. The stump pressure had no correlation with CBF and rSO(2). Conclusions The rSO(2) significantly correlated with CBF from SPECT and related with appearance of symptoms. Our results revealed that rSO(2) monitoring was useful in BTO, and SPECT could be skipped in some cases. to determine the strategies for treatment of IC large aneurysms.

  230. くも膜下出血の周術期に使用した少量のヘパリンでII型ヘパリン起因性血小板減少症(HIT Type II)を発症し,アルガトロバン投与が有効であった1例 Peer-reviewed

    松本 康史, 近藤 竜史, 新妻 邦泰, 坪井 謙, 古井 英介, 江面 正幸, 高橋 明

    Therapeutic Research 26 (11) 2173-2177 2005/11

  231. PowerPointによるプレゼンテーション資料作成の効率化

    新妻 邦泰, 冨永 悌二

    Neurological Surgery 33 (8) 832-837 2005/08

  232. 傍側脳室部海綿状血管腫の1手術例 手術法決定におけるFiber Trackingの有用性 Peer-reviewed

    新妻 邦泰, 隈部 俊宏, 日向野 修一, 冨永 悌二

    新潟医学会雑誌 118 (10) 539-540 2004/10

  233. 膠芽腫と有鉤嚢虫症を合併したTurcot症候群の一例 Peer-reviewed

    新妻邦泰, 隈部俊宏, 藤村幹, 渡辺みか, 冨永悌二, 嘉山孝正

    Brain Tumor Pathology 21 (Suppl.) 52-52 2004/05

  234. Exclusively extradural arteriovenous malformation with neurogenic claudication - Case illustration Peer-reviewed

    K Niizuma, M Fujimura, T Takahashi, A Takahashi, M Watanabe, T Tominaga

    JOURNAL OF NEUROSURGERY 100 (4) 397-397 2004/04

    Publisher: AMER ASSOC NEUROLOGICAL SURGEONS

    ISSN:0022-3085

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    Case Illustration<br /> http://thejns.org/doi/pdf/10.3171/spi.2004.100.4.0397

Show all ︎Show first 5

Misc. 95

  1. 【脳動脈瘤の温故知新 現在までの治療を紡ぐ永久保存版】脳血管攣縮の最新治療

    遠藤 英徳, 新妻 邦泰, 冨永 悌二

    脳神経外科速報 33 (2) 208-210 2023/03

    Publisher: (株)メディカ出版

    ISSN:0917-1495

  2. [Stem Cell Therapy for Neurological Diseases].

    Kuniyasu Niizuma

    Brain and nerve = Shinkei kenkyu no shinpo 75 (2) 167-172 2023/02

    DOI: 10.11477/mf.1416202299  

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    Recently, regenerative medicine, a field of medicine which focuses on the repair or replacement of damaged or lost tissues, has been of great interest. Although stem cell therapies for neurological diseases are still controversial, recent studies demonstrated positive treatment effects. In this review, stem cell therapy mechanisms are described focusing on recent findings. Moreover, clinical trial results are also summarized.

  3. Cerebrovascular disease in children treated in our single institution

    君和田友美, 林俊哲, 佐藤健一, 新妻邦泰, 新妻邦泰, 冨永悌二

    小児の脳神経(Web) 48 (2) 2023

    ISSN:2435-824X

  4. 【計画的セレンディピティが医学・創薬を革新する!】脳梗塞治療の計画的セレンディピティ

    新妻 邦泰

    医学のあゆみ 282 (9) 817-821 2022/08

    Publisher: 医歯薬出版(株)

    ISSN:0039-2359

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    脳梗塞とは、脳を栄養する血管が閉塞あるいは狭窄することにより、その灌流領域に十分な酸素や栄養が供給されなくなり、結果として脳神経細胞が障害されてしまう疾患である。脳梗塞になると半数以上に後遺症が残存するが、近年は脳が傷つく前に閉塞した血管を再開通させる再開通療法により治療を受けることができた患者の成績が著しく向上している。ただし、脳が傷んだ後に再開通させてしまうと出血性変化が生じて状態が悪化するために厳しい時間制限があり、再開通療法を受けられる患者は10%程度である。Stachybotrys microspore triprenyl phenol(SMTP)化合物とは血栓溶解作用と抗炎症作用を併せ持つ化合物であり、出血性変化を抑制しながら再開通させることが期待できる新規薬剤であり、SMTP化合物を用いた脳梗塞治療の第II相治験まで終了した段階である。本稿では、SMTPの開発経過を概説するとともに、計画的セレンディピティについて考察する(SMTPの開発は"計画的ではない"セレンディピティの塊であったが…)。(著者抄録)

  5. 高拍出性心不全を呈し血管内治療を行った新生児2例

    熊井 萌, 君和田 友美, 佐藤 健一, 新妻 邦泰, 林 俊哲, 萩野 有正, 渡邉 達也, 室月 淳, 菊地 千歌, 五十嵐 あゆ子, 木村 正人, 田中 高志, 冨永 悌二

    小児の脳神経 47 (2) 242-242 2022/04

    Publisher: (一社)日本小児神経外科学会

    ISSN:0387-8023

    eISSN:2435-824X

  6. 言語症状に対する内観と失語型との対応 超選択的Wadaテストによる検討

    柿沼 一雄, 大沢 伸一郎, 細川 大瑛, 親富祖 まりえ, 太田 祥子, 浮城 一司, 石田 誠, 神 一敬, 中里 信和, 新妻 邦泰, 冨永 悌二, 鈴木 匡子

    高次脳機能研究 42 (1) 97-97 2022/03

    Publisher: (一社)日本高次脳機能障害学会

    ISSN:1348-4818

    eISSN:1880-6554

  7. 【脳梗塞-急性期治療の進歩と今後の課題】脳梗塞急性期の細胞療法の現状と展開

    新妻 邦泰

    カレントテラピー 40 (3) 257-262 2022/03

    Publisher: (株)ライフメディコム

    ISSN:0287-8445

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    tPA静注療法や血栓回収療法などの再開通療法の発達により、脳梗塞急性期治療は目覚ましい発展を遂げたが、治療可能時間枠が短いため、再開通療法の対象となる患者は10%程度にすぎない。そのため、大半の患者は脳梗塞が完成してしまうため、梗塞に陥った脳を再生させうる幹細胞治療に期待が集まっている。現在までに脳梗塞に対する幹細胞治療には確固たるエビデンスはないが、超急性期の幹細胞治療が有望と考えられており、他家製剤による治験が遂行されている。また、幹細胞による治療メカニズムも明らかになりつつあり、それに基づき最適化された治療法出現も期待される。われわれのグループは、生体内に存在し、さまざまな組織に分化する多能性と安全性を併せもつMuse細胞を用い、脳梗塞急性期あるいは亜急性期細胞治療の研究を重ね、治験にまで到達した。本稿では、急性期細胞治療につき概説するとともに、Muse細胞治療についても紹介する。(著者抄録)

  8. 【脊髄損傷の治療アップデート】Muse細胞を用いた脊髄損傷に対する治療

    遠藤 俊毅, 新妻 邦泰, 冨永 悌二

    関節外科 41 (3) 231-236 2022/03

    Publisher: (株)メジカルビュー社

    ISSN:0286-5394

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    <文献概要>骨髄由来の多能性幹細胞であるMuse細胞は,経静脈的に投与されると傷害組織に遊走し,その場に必要な細胞に分化して臓器修復を行う。Muse細胞は高い安全性と多能性を有し,細胞治療の有力なソースとして近年注目を集めている。本稿では,脊髄損傷ラットモデルにヒトMuse細胞製品(CL2020)を移植した基礎研究の結果と現在行われている多施設共同臨床治験について紹介し,脊髄損傷に対するMuse細胞移植治療の可能性について述べる。

  9. MR-拡散テンソル画像による咬筋筋線維画像化の最適方法に関する検討

    菅野 武彦, 依田 信裕, 小川 徹, 橋本 照男, 庄原 健太, 新妻 邦泰, 川島 隆太, 佐々木 啓一

    日本補綴歯科学会誌 13 (特別号) 247-247 2021/06

    Publisher: (公社)日本補綴歯科学会

    ISSN:1883-4426

    eISSN:1883-6860

  10. MR-拡散テンソル画像による咬筋筋線維画像化の最適方法に関する検討

    菅野 武彦, 依田 信裕, 小川 徹, 橋本 照男, 庄原 健太, 新妻 邦泰, 川島 隆太, 佐々木 啓一

    日本補綴歯科学会誌 13 (特別号) 247-247 2021/06

    Publisher: (公社)日本補綴歯科学会

    ISSN:1883-4426

    eISSN:1883-6860

  11. 【脳梗塞と闘う】Muse細胞による新規脳梗塞治療法の開発

    新妻 邦泰, 冨永 悌二

    日本血栓止血学会誌 32 (3) 296-302 2021/06

    Publisher: (一社)日本血栓止血学会

    ISSN:0915-7441

    eISSN:1880-8808

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    脳梗塞とは、脳を栄養する血管が閉塞もしくは狭窄することにより、その灌流領域に血流不全が生じ十分な酸素や栄養が供給されなくなり、結果として脳神経細胞が傷害されてしまう疾患である。近年の血栓溶解薬やカテーテル治療の進歩により脳梗塞の転帰は改善してきているものの、未だそれらの再開通療法の適応となる患者は10%未満であり、大半の患者には脳梗塞が完成することになる。脳は脆弱な組織であり、かつ再生能力が限定的であることから、完成した脳梗塞に対する根本的な治療は存在しなかったが、近年では幹細胞治療により脳を再生させられる可能性が見いだされ期待が集まっている。本稿では脳梗塞に対する幹細胞治療の現状を概説後、Muse細胞を用いた新規治療開発につき述べる。(著者抄録)

  12. 【神経修復・再生の最前線】Muse細胞を用いた神経再生医療の実現

    新妻 邦泰

    BIO Clinica 36 (4) 310-314 2021/04

    Publisher: (株)北隆館

    ISSN:0919-8237

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    脳梗塞の患者数は高齢化に伴い増加傾向であり、既存の如何なる治療法を用いても脳梗塞に陥った組織を回復させられないため、半数以上に障害が後遺するため。従って、脳組織自体を再生させ得る幹細胞治療に期待が集まっている。Muse細胞は生体に存在する自然の多能性幹細胞であり、腫瘍化の危険が極めて低く安全性が高い。Muse細胞は血管内や局所に投与するだけで傷害部位を認識して生着し、組織に応じた細胞に自発的に分化して修復する。本稿では脳梗塞に対する幹細胞治療の現状と、Muse細胞を用いた新規治療開発につき概説する。(著者抄録)

  13. Muse細胞による神経再生医療の開発

    新妻 邦泰, 冨永 悌二

    神経心理学 37 (1) 21-28 2021/03

    Publisher: 日本神経心理学会

    ISSN:0911-1085

    eISSN:2189-9401

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    脳梗塞は脳卒中全体の約6割を占め,高齢化に伴い患者数は増加傾向である.既存の如何なる治療法を用いても脳梗塞に陥った組織を回復させられないため,脳組織自体を再生させ得る幹細胞治療に期待が集まっている.Muse細胞は生体に存在する自然の多能性幹細胞であり,腫瘍形成のリスクが低く,安全性が高いと考えられている.Muse細胞は血管内や局所に投与するだけで傷害部位を認識して生着し,組織に応じた細胞に自発的に分化して修復することと合わせ,有力な幹細胞治療のソースと考えられている.本稿では脳梗塞に対する幹細胞治療の現状と,Muse細胞を用いた新規治療開発につき概説する.(著者抄録)

  14. A Case of Cavernous Sinus Dural Arteriovenous Fistula Successfully Treated by Transarterial Embolization with Embosphere

    CHEN Mengge, 大沢伸一郎, 新妻邦泰, 遠藤英徳, 冨永悌二

    脳血管内治療(Web) 6 (1) 2021

    ISSN:2424-1709

  15. Muse細胞を用いたてんかん原性治癒手法の確立

    大沢伸一郎, 新妻邦泰, 新妻邦泰, 冨永悌二

    てんかん治療研究振興財団研究年報 32 2021

    ISSN:0915-5902

  16. 【脊椎・脊髄損傷-診断・治療の最前線と今後の展望】脊髄損傷に対するMuse細胞移植治療

    遠藤 俊毅, 新妻 邦泰, 梶谷 卓未, 高橋 義晴, 鈴木 晋介, 冨永 悌二

    脊椎脊髄ジャーナル 33 (10) 926-930 2020/10

    Publisher: (株)三輪書店

    ISSN:0914-4412

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    <文献概要>はじめに 脊髄損傷は,交通事故や転落などの強い外力が脊髄にかかることによって引き起こされる.脊髄損傷は運動感覚障害,膀胱直腸障害を引き起こし,患者の日常生活動作(ADL)は著しく低下する.現在,脊髄損傷に対する根本的な治療は,残念ながらまだない.しかし,近年,外因性の幹細胞移植により治療するさまざまな取り組みがなされている.細胞ソースとしては,神経幹細胞やinduced pluripotent stem(iPS)細胞,間葉系幹細胞,単核球細胞などが用いられ,特に札幌医科大学とニプロ社により開発された,自己骨髄由来間葉系幹細胞を用いた再生医療等製品「ステミラック注」が「条件及び期限付製造販売承認」を取得するなど,脊髄損傷に対する再生医療に新たな展開が訪れている.

  17. DTIを応用した咬筋内部の筋線維三次元描出および走行解析

    菅野 武彦, 依田 信裕, 小川 徹, 橋本 照男, 新妻 邦泰, 川島 隆太, 佐々木 啓一

    日本補綴歯科学会誌 12 (特別号) 130-130 2020/06

    Publisher: (公社)日本補綴歯科学会

    ISSN:1883-4426

    eISSN:1883-6860

  18. 【内科医として知っておくべき非がん疾患の手術】脳神経外科領域の手術 未破裂脳動脈瘤

    新妻 邦泰

    内科 125 (5) 1179-1182 2020/05

    Publisher: (株)南江堂

    ISSN:0022-1961

    eISSN:2432-9452

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    <文献概要>▼未破裂脳動脈瘤は一般的に無症状で,治療は破裂を予防するための予防治療になるため,手術適応は慎重に判断する必要がある.▼個々の破裂リスクもある程度算出可能であるため,平均余命および手術リスクをあわせて手術適応を決定する.▼増大例は高リスクのため,外科的治療をしない場合には経過観察が必要である.▼患者に過度の心理的負担をかけないように配慮が必要である.

  19. Progress of cell therapy for cerebral infarction Invited

    Kuniyasu NIIZUMA

    30 (5) 498-505 2020/05

    Publisher: (株)メディカ出版

    ISSN:0917-1495

  20. Muse細胞を用いたてんかん原性治癒手法の確立

    大沢 伸一郎, 新妻 邦泰, 冨永 悌二

    Medical Science Digest 46 (2) 124-126 2020/02

    Publisher: (株)ニュー・サイエンス社

    ISSN:1347-4340

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    Muse細胞は生体に存在する自然の多能性幹細胞であり、安全性と組織修復性を両立した珍しい特徴ゆえに、細胞治療の有力なソースとして注目されている。既に我々は脳梗塞モデルにおいて本細胞を用いて再生医療研究を行い、安全性・有効性を実証してきた。てんかんは良性疾患であり慢性に経過するため、一般的に遺伝子操作を必要とする治療のハードルは高く、再生医療の試みは未だ報告が少ない。しかしMuse細胞は生成に遺伝子導入を必要とせず、その安全性はてんかん治療に対して有利と考えられる。一方で我々はオプトジェネティクスによるラット海馬光誘発けいれんモデルを開発し、その迅速性・確実性・再現性・低死亡率を活かして安定した実験環境を構築した。本モデルを用いてけいれん発作を誘発した後にMuse細胞投与を行い、脳内損傷部位への細胞生着および修復能力に期待し研究を進めている。(著者抄録)

  21. 成人もやもや病に対するバイパス術後の遅発性過灌流とRNF213遺伝子c.14576G>A多型の関連についての検討

    藤村幹, 田代亮介, 勝木将人, 西澤威人, 遠又靖丈, 新妻邦泰, 冨永悌二

    脳循環代謝(Web) 32 (1) 2020

    ISSN:2188-7519

  22. 2 cases of prepontine cistern-3rd ventricle epidermoid cyst resected under endoscope with manual jet technique

    新妻邦泰, 新妻邦泰, 新妻邦泰, 石田朋久, 大沢伸一郎, 遠藤英徳, 冨永悌二

    日本神経内視鏡学会プログラム・抄録集 27th 2020

  23. 超選択的Wada testによるオーダーメイド的局所脳機能評価

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 上利大, 新妻邦泰, 新妻邦泰, 神一敬, 浅黄優, 中里信和, 冨永悌二

    臨床神経生理学(Web) 48 (5) 2020

    ISSN:2188-031X

  24. オーダーメイド的脳機能評価における超選択的Wada testの有用性

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 上利大, 新妻邦泰, 神一敬, 中里信和, 冨永悌二

    日本てんかん外科学会プログラム・抄録集 43rd 2020

  25. Order-made evaluation of brain function by super-selective Wada test in the candidate patients of epilepsy surgery

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 上利大, 新妻邦泰, 神一敬, 中里信和, 冨永悌二

    日本ヒト脳機能マッピング学会プログラム・抄録集 22nd 2020

  26. Actualization of Neural Regenerative Medicine by Intravenous Drip of Donor-derived Muse Cells

    Dezawa M, Niizuma K, Tominaga T

    Brain and nerve = Shinkei kenkyu no shinpo 71 (8) 895-900 2019/08

    DOI: 10.11477/mf.1416201372  

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    Muse cells are non-tumorigenic reparative endogenous stem cells identified by SSEA-3+. They are pluripotent and are stably mobilized from the bone marrow to the peripheral blood and distribute to organ connective tissue, where they contribute to daily minute repair of damaged/lost cells by spontaneous differentiation into tissue-constituent cells. Muse cells specifically home to damaged site to repair the tissue by simultaneous differentiation into multiple tissue-constituent cells. When the number of endogenous Muse cells is not sufficient, administration of exogenous Muse cells delivers robust functional recovery. Muse cells do not need to be "induced" or genetically manipulated. Intravenous drip is the main method of administration, making surgical operation unnecessary. Because Muse cells have an immunomodulatory system similar to the placenta, donor-derived Muse cells can be directly administered to patients without HLA-matching or immunosuppression therapy. Allogeneic Muse cells remain in the host tissue as differentiated cells for more than half a year. Clinical trials for the treatment of myocardial infarction, stroke and epidermolysis bullosa with intravenous injection of donor-derived Muse cells are currently conducted by the Life Science Institute Inc. Muse cells may safely provide clinically relevant effects compatible with the 'body's natural repair systems' by a simple cost-effective strategy.

  27. 【高齢者を脳卒中から守る・救う】未破裂脳動脈瘤診療の実際

    新妻 邦泰

    Geriatric Medicine 57 (5) 469-474 2019/05

    Publisher: (株)ライフ・サイエンス

    ISSN:0387-1088

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    ■長寿国である本邦では高齢者に未破裂脳動脈瘤が発見される可能性も高く、その治療方針を決定するのが難しい場合も多い。未破裂脳動脈瘤は原則として無症候性で、破裂を予防するための予防治療になるため、手術適応は慎重に判断する必要がある。経過観察方針となる瘤が多くはなるが、比較的リスクの高い高齢者未破裂動脈瘤も明らかになってきており、リスクベネフィットを考え、必要であれば外科治療も考えるべきである。(著者抄録)

  28. 脳生検により炎症性脱髄性疾患である可能性が示唆された嗜眠性脳炎の1例

    大野尭之, 高井良樹, 鈴木直輝, 菅野直人, 小野理佐子, 黒田宙, 勝木将人, 西嶌泰生, 新妻邦泰, 渡辺みか, 神林崇, 青木正志

    臨床神経学(Web) 59 (7) 2019

    ISSN:1882-0654

  29. 超選択的Wada testによるオーダーメイド的脳機能評価

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 上利大, 浅黄優, 新妻邦泰, 三木俊, 神一敬, 中里信和, 中里信和, 冨永悌二

    臨床神経生理学(Web) 47 (5) 2019

    ISSN:2188-031X

  30. 超選択的Wada testによる血管解剖と機能解剖のハイブリッド評価

    大沢伸一郎, 鈴木匡子, 新妻邦泰, 新妻邦泰, 浮城一司, 柿沼一雄, 上利大, 神一敬, 斎藤竜太, 金森政之, 中里信和, 冨永悌二

    脳血管内治療(Web) 4 (Supplement) 2019

    ISSN:2424-1709

  31. 【Muse細胞-現状と将来展望-】 脳梗塞におけるMuse細胞を用いた治療戦略

    新妻 邦泰, 冨永 悌二

    血液フロンティア 29 (2) 185-195 2019/01

    Publisher: (株)医薬ジャーナル社

    ISSN:1344-6940

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    <文献概要>脳梗塞は脳卒中全体の約6割を占める。既存の如何なる治療法を用いても,脳梗塞に陥った組織を回復させられないため,半数以上に障害が後遺する。したがって,脳組織自体を再生させうる幹細胞治療に期待が集まっている。Muse細胞(Multilineage-differentiating stress enduring cell)は生体に存在する自然の多能性幹細胞であり,腫瘍性を持たず安全性が高い。Muse細胞は血管内や局所に投与するだけで傷害部位を認識して生着し,組織に応じた細胞に自発的に分化して修復する。目的とする細胞への事前の誘導操作を必要とせず,投与するだけで再生治療が可能である。本稿では,本邦で取り組まれている脳梗塞に対する幹細胞治療を概説するとともに,脳梗塞に対するMuse細胞治療の可能性につき述べる。

  32. 脳梗塞におけるMuse細胞を用いた治療戦略 Invited

    新妻 邦泰, 冨永 悌二

    血液フロンティア 29 (2) 47-57 2019/01

  33. 脳動脈瘤の出血源診断における造影MRIの有用性

    面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 佐藤 健一, 藤村 幹, 松本 康史, 井上 敬, 冨永 悌二

    東北脳血管障害研究会学術集会記録集 40回 0076-0091 2018/12

    Publisher: サノフィ(株)仙台オフィス

    ISSN:1880-9278

  34. バイオマーカーによる脳卒中診断

    井上 敬, 石田 邦久, 新妻 邦泰, 井上 智夫, 齋藤 敦志, 江面 正幸, 遠藤 英徳, 藤村 幹, 冨永 悌二

    脳循環代謝 30 (1) 119-119 2018/10

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

  35. 選択的後大脳動脈Wada testによる海馬機能評価

    大沢伸一郎, 岩崎真樹, 鈴木匡子, 新妻邦泰, 松本康史, 神一敬, 中里信和, 冨永悌二

    てんかん研究 36 (2) 420-420 2018/09/12

    Publisher: (一社)日本てんかん学会

    ISSN:0912-0890

  36. 開頭手術と血管内治療の複合治療 4 dAVF 横静脈洞‐S状静脈洞部dAVF

    新妻邦泰, 新妻邦泰, 遠藤英徳, 松本康史, 冨永悌二

    脳神経外科速報 (2018増刊) 254-264 2018/09

    Publisher: (株)メディカ出版

    ISSN:0917-1495

  37. 精密血管評価に基づく巨大下垂体腺腫摘出 術中出血制御と術後下垂体卒中抑制を目的として

    油川 大輝, 小川 欣一, 佐藤 健一, 新妻 邦泰, 冨永 悌二

    Neurological Surgery 46 (8) 691-697 2018/08

    Publisher: (株)医学書院

    ISSN:0301-2603

    eISSN:1882-1251

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    症例は43歳女性で、42歳時に両耳側半盲とトルコ鞍部腫瘍を指摘され当科紹介となった。MRIでトルコ鞍内から鞍上部に伸展する巨大な腫瘤影を認め、3方向性volume rendering imageとCT様3方向像を再構成し手術計画を策定した。その結果、左meningohypophyseal trunk(MHT)から腫瘍後下壁に沿って求心性の栄養血管が認められ、同時に同血管より腫瘍内部を後方から前下方に走行する太い動脈がreconstituteされる遠心性の腫瘍栄養が確認された。一方、左superior hypophyseal artery(SHA)からも、腫瘍の左側面に沿って後方からの求心性の腫瘍栄養が確認された。さらに、右MHTからも腫瘍の前下方壁に沿って内上方に走行する血管からの求心性の腫瘍栄養を認めたが、左右の内頸動脈撮影を比較すると、明らかに左で強いtumor stainが認められた。以上の所見から、左MHTおよび左SHAからの血流を処理しやすい拡大経蝶形骨洞手術で摘出する方針とした。術後、視野欠損は消失し、独歩にて自宅退院となった。

  38. 【閉塞性血管障害病変の課題と展望】 CEAとCASの適応と課題

    遠藤 英徳, 藤村 幹, 松本 康史, 遠藤 俊毅, 佐藤 健一, 新妻 邦泰, 井上 敬, 冨永 悌二

    脳神経外科ジャーナル 27 (7) 514-521 2018/07

    Publisher: 日本脳神経外科コングレス

    ISSN:0917-950X

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    頸動脈狭窄症に対する外科治療の是非に関して、これまで数多くのランダム化比較試験(RCT)が行われてきた。古くは、内膜剥離術(CEA)と内科治療を比較したRCT、その後CEAと頸動脈ステント留置術(CAS)を比較したRCTが行われ、その結果に基づいて治療ガイドラインが作成された。症候性高度狭窄に対してはCEAもしくはCASの有効性が示されているが、内科治療が発展した現在においては、無症候性病変に対する外科治療の有効性検証が課題である。今後は、外科治療の危険因子を抽出し、治療対象を明確化していく必要があるとともに、術者教育環境を整え、治療成績の維持・向上に努める必要がある。(著者抄録)

  39. 小児もやもや病に対する直接間接複合バイパス術―長期治療成績と課題―

    藤村幹, 遠藤英徳, 新妻邦泰, 冨永悌二

    Mt. Fuji Workshop on CVD 36 1-4 2018/07

    Publisher: (株)にゅーろん社

    ISSN:0289-8438

  40. 神経疾患の再生医療 間葉系幹細胞による研究 脳卒中モデルに対するMuse細胞移植の効果

    内田浩喜, 新妻邦泰, 出澤真理, 冨永悌二

    Clinical Neuroscience 36 (3) 356‐360 2018/03/01

    ISSN:0289-0585

  41. 選択的後大脳動脈Wada testによる海馬機能評価

    大沢伸一郎, 新妻邦泰, 新妻邦泰, 鈴木匡子, 岩崎真樹, 佐藤健一, 遠藤英徳, 松本康史, 神一敬, 中里信和, 冨永悌二

    脳血管内治療(Web) 3 (Supplement) 2018

    ISSN:2424-1709

  42. パルスウォータージェットメスの開発:切開深達度均一化に関する検討

    野口侑太, 中川敦寛, 楠哲也, 中西史, 横沢友樹, 山下慎一, 佐藤由加, 遠藤俊毅, 遠藤英徳, 新妻邦泰, 飯久保正弘, 冨永悌二

    日本生体医工学会大会プログラム・抄録集(Web) 57th 2018

  43. ピエゾ駆動方式パルスウォータージェットメス開発:軟性内視鏡下の使用を想定したパルスジェット特性の検討

    楠哲也, 中川敦寛, 野口侑太, 中西史, 横沢友樹, 山下慎一, 佐藤由加, 遠藤俊毅, 遠藤英徳, 新妻邦泰, 飯久保正弘, 冨永悌二

    日本生体医工学会大会プログラム・抄録集(Web) 57th 2018

  44. ラット静脈洞血栓症モデルにおける,脳血流変化の観察

    濱崎亮, 新妻邦泰, RASHAD Sherif, 高橋和孝, 清水宏明, 冨永悌二

    日本分子脳神経外科学会プログラム・抄録集 19th 2018

  45. ラット上矢静脈洞血栓症モデルにおける,脳血流変化の観察

    濱崎亮, 濱崎亮, 新妻邦泰, 新妻邦泰, RASHAD Sherif, 清水宏明, 冨永悌二

    脳循環代謝(Web) 30 (1) 2018

    ISSN:2188-7519

  46. 臨床研究推進センター再生医療ユニットの再生・細胞医療シーズの活性化に向けた細胞提供の取り組み

    伊藤貴子, 伊藤貴子, 沖田ひとみ, 吉田まなみ, 新妻邦泰, 若尾昌平, 出澤真理, 冨永悌二, 張替秀郎, 後藤昌史, 下川宏明

    日本再生医療学会総会(Web) 17th ROMBUNNO.P‐01‐120 (WEB ONLY) 2018

  47. Current Indications and Problems of CEA and CAS

    遠藤英徳, 藤村幹, 松本康史, 遠藤俊毅, 佐藤健一, 新妻邦泰, 井上敬, 冨永悌二

    脳神経外科ジャーナル 27 (7) 514‐521(J‐STAGE) 2018

    DOI: 10.7887/jcns.27.514  

    ISSN:0917-950X

  48. エンボスフィアを用いたTAEで根治し得た海綿静脈洞部硬膜動静脈瘻の一治療例

    新妻 邦泰, 坂田 洋之, 大沢 伸一郎, 遠藤 英徳, 松本 康史, 冨永 悌二

    脳血管内治療 2 (Suppl.) S204-S204 2017/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

  49. Choroidal arteryを標的としたAVM塞栓術の治療成績

    遠藤 英徳, 松本 康史, 佐藤 健一, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二

    脳血管内治療 2 (Suppl.) S32-S32 2017/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  50. 造影MRIを用いた多発脳動脈瘤の出血源診断

    面高 俊介, 遠藤 英徳, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 佐藤 健一, 松本 康史, 冨永 悌二

    脳血管内治療 2 (Suppl.) S269-S269 2017/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  51. 新規脳梗塞治療薬SMTP-7の開発

    新妻邦泰, 藤村幹, 清水宏明, 冨永悌二

    脳循環代謝(Web) 29 (1) 2017

    ISSN:2188-7519

  52. マウス一過性中大脳動脈閉塞モデルにおけるimaging mass spectrometryによるメタボローム解析

    阿部考貢, 新妻邦泰, 鹿毛淳史, 藤村幹, 三枝大輔, 宇留野晃, 山本雅之, 冨永悌二

    日本分子脳神経外科学会プログラム・抄録集 18th 2017

  53. コイル塞栓術後再開通により破裂した脳動脈瘤に関する数値流体力学的解析

    園部 真也, 杉山 慎一郎, 松本 康史, 遠藤 英徳, 新妻 邦泰, 冨永 悌二

    脳血管内治療 1 (Suppl.) S248-S248 2016/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

  54. Choroidal arteryを標的としたAVM塞栓術の治療成績

    遠藤 英徳, 松本 康史, 佐藤 健一, 近藤 竜史, 新妻 邦泰, 遠藤 俊毅, 藤村 幹, 冨永 悌二

    脳血管内治療 1 (Suppl.) S98-S98 2016/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

    eISSN:2424-1709

  55. 待機手術を施行した脊髄軟膜動静脈瘻の1治療例

    新妻 邦泰, 佐藤 健一, 遠藤 俊毅, 眞野 唯, 赤松 洋祐, 藤村 幹, 冨永 悌二

    脳血管内治療 1 (Suppl.) S130-S130 2016/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:2423-9119

  56. 症状動揺性が目立たず緩徐進行性下肢感覚障害を呈した脊髄硬膜動静脈瘻の一例

    中村 尚子, 佐藤 遼佑, 西山 修平, 黒田 宙, 青木 正志, 新妻 邦泰, 遠藤 俊毅

    臨床神経学 56 (11) 807-807 2016/11

    Publisher: (一社)日本神経学会

    ISSN:0009-918X

  57. 脳動脈瘤における血液滞留時間と動脈硬化性変化との関係

    杉山 慎一郎, 遠藤 英徳, 新妻 邦泰, 冨永 悌二

    脳循環代謝 28 (1) 165-165 2016/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  58. 成人もやもや病に対する直接間接複合バイパス術 脳循環画像に基づいた周術期管理の効果とpitfall

    藤村 幹, 坂田 洋之, 新妻 邦泰, 遠藤 英徳, 井上 敬, 冨永 悌二

    脳循環代謝 28 (1) 182-182 2016/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  59. 脳梗塞モデルにおけるMuse細胞移植

    新妻 邦泰, 出澤 真理, 冨永 悌二

    Clinical Neuroscience 34 (10) 1098-1101 2016/10

  60. Reperfusion and Neurovascular Dysfunction in Stroke: from Basic Mechanisms to Potential Strategies for Neuroprotection

    Joo Eun Jung, Gab Seok Kim, Hai Chen, Carolina M. Maier, Purnima Narasimhan, Yun Seon Song, Kuniyasu Niizuma, Masataka Katsu, Nobuya Okami, Hideyuki Yoshioka, Hiroyuki Sakata, Christina E. Goeders, Pak H. Chan

    Mol Neurobiol 41 (2-3) 172-179 2016/06

    DOI: 10.1007/s12035-010-8102-z  

    More details Close

    First Online:17 February 2010

  61. プラスミノゲン活性化を促進する新規脳梗塞治療薬の非臨床および臨床開発

    蓮見 惠司, 西村 直子, 長谷川 啓子, 鈴木 絵里子, 澤田 裕伸, 本田 一男, 冨永 悌二, 新妻 邦泰, 若林 祐里江, 森豊 隆志, 山崎 力, 東大病院, ユニット試験実施グループ

    日本血栓止血学会誌 27 (2) 263-263 2016/05

    Publisher: (一社)日本血栓止血学会

    ISSN:0915-7441

  62. 神経外傷とBiomedical Informatics 集中治療分野におけるビッグデータ解析と、今後の展望

    小林 直也, 中川 敦寛, 江島 豊, 齋藤 浩二, 吾妻 俊弘, 外山 裕章, 遠藤 康弘, 川口 奉洋, 新妻 邦泰, 工藤 大介, 久志本 成樹, 渡邉 一規, 佐藤 健, 冨永 悌二, 山内 正憲

    日本脳神経外傷学会プログラム・抄録集 39回 64-64 2016/02

    Publisher: (一社)日本脳神経外傷学会

  63. 頭蓋頸椎移行部病変をふくむ頸髄perimedullary AVSの臨床像 連続22症例の検討から

    遠藤 俊毅, 佐藤 健一, 新妻 邦泰, 松本 康史, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 9 (6) S227-S227 2015/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

  64. ONYXはAVMの治療成績を向上させたか? 脳動静脈奇形に対する集学的治療における血管内治療

    新妻 邦泰, 佐藤 健一, 松本 康史, 遠藤 英徳, 藤村 幹, 近藤 竜史, 川岸 潤, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 9 (6) S191-S191 2015/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

    eISSN:2186-2494

  65. 小児もやもや病に対する直接間接複合バイパス術 長期治療成績の検討

    藤村 幹, ラシャド・シェリフ, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 佐藤 健一, 冨永 悌二

    脳循環代謝 27 (1) 139-139 2015/10

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  66. 深部脳動静脈奇形周囲にcerebral proliferative angiopathyの2次的形成を認めた小児例

    坂田 洋之, 藤村 幹, 佐藤 健一, 新妻 邦泰, 遠藤 英徳, 冨永 悌二

    脳循環代謝 27 (1) 190-190 2015/10

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  67. 無症候性脳血管障害へのアプローチ

    新妻 邦泰, 冨永 悌二

    脳と循環 20 (3) 245-250 2015/09

  68. Required knowledge for stroke specialists (9) asymptomatic cerebrovascular diseases

    Kuniyasu NIIZUMA, Teiji TOMINAGA

    Neurological Surgery 43 (4) 357-368 2015/04/10

    DOI: 10.11477/mf.1436203022  

  69. 頸椎脱臼骨折整復術前の予防的椎骨動脈塞栓術の二例

    新妻 邦泰, 川口 奉洋, 佐藤 健一, 藤村 幹, 遠藤 俊毅, 笹治 達郎, 松本 康史, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 8 (6) 382-382 2014/12

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

  70. 破裂瘤の治療後早期に破裂した前交通動脈瘤の一例 血行力学的変化の検討

    新妻 邦泰, 杉山 慎一郎, 遠藤 英徳, 佐藤 健一, 松本 康史, 藤村 幹, 冨永 悌二

    脳循環代謝 26 (1) 166-166 2014/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  71. CEA術前後にSPECTは必須か?

    井上 敬, 藤村 幹, 佐藤 健一, 遠藤 英徳, 新妻 邦泰, 坂田 洋之, 江面 正幸, 上之原 広司, 藤原 悟, 冨永 悌二

    脳循環代謝 26 (1) 200-200 2014/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

    eISSN:2188-7519

  72. もやもや病疾患感受性遺伝子RNF213 R4859K変異マウスにおける経時的頭部MRA所見に関する検討

    鹿毛 淳史, 藤村 幹, 新妻 邦泰, 坂田 洋之, 伊藤 明, 前田 美香, 呉 繁夫, 冨永 悌二

    脳循環代謝 26 (1) 180-180 2014/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

  73. もやもや病疾患感受性遺伝子RNF213ノックアウトマウスの一過性局所脳虚血への反応性の検討

    伊藤 明, 藤村 幹, 新妻 邦泰, 坂田 洋之, 鹿毛 淳史, 呉 繁夫, 冨永 悌二

    脳循環代謝 26 (1) 208-208 2014/11

    Publisher: 日本脳循環代謝学会

    ISSN:0915-9401

  74. Roles of p53 signaling pathway in neuronal cell death after cerebral ischemia

    Kuniyasu Niizuma, Teiji Tominaga

    Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism) 25 (2) 117-121 2014/11

    Publisher: The Japanese Society of Cerebral Blood Flow and Metabolism

    DOI: 10.16977/cbfm.25.2_117  

    ISSN:0915-9401

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    Various signaling pathways are activated after cerebral ischemia. p53 plays important roles in regulation of apoptotic pathways. p53 transcriptionally activates mitochondria-dependent apoptotic pathway that involves pro- and antiapoptotic protein binding, the release of cytochrome <i>c</i> and apoptosis-inducing factor, leading to neuronal death after cerebral ischemia. In this report, we summarize this signaling pathway, focusing on Bcl-2-associated X protein (Bax), p53-upregulated modulator of apoptosis (PUMA), and p53-induced protein with a death domain (PIDD).

  75. 脳血管内治療における数値流体力学 CFD(Computational Fluid Dynamics)の最前線 初心者のための脳動脈瘤CFD解析のパラダイムシフト

    木村 尚人, 高尾 洋之, 中山 敏男, 面高 俊介, 杉山 伸一郎, 新妻 邦泰, 藤村 幹, 井上 敬, 江面 正幸, 山本 誠, 村山 雄一, 冨永 悌二

    脳神経外科速報 24 (7) 758-762 2014/07

  76. 脳血管内治療における数値流体力学~CFD(Computational Fluid Dynamics)の最前線 脳動脈瘤壁の硬化性変化

    新妻 邦泰, 杉山 慎一郎, 遠藤 英徳, 松本 康史, 冨永 悌二

    脳神経外科速報 24 (6) 640-643 2014/06

    Publisher: (株)メディカ出版

    ISSN:0917-1495

  77. Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene

    Miki Fujimura, Shinya Sonobe, Yasuo Nishijima, Kuniyasu Niizuma, Hiroyuki Sakata, Shigeo Kure, Teiji Tominaga

    JOURNAL OF STROKE 16 (2) 65-72 2014/05

    Publisher: KOREAN STROKE SOC

    DOI: 10.5853/jos.2014.16.2.65  

    ISSN:2287-6391

    eISSN:2287-6405

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    Moyamoya disease is characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, recent genome-wide and locus-specific association studies identified RNF213 as an important susceptibility gene of moyamoya disease among East Asian population. A polymorphism in c.14576G &gt; A in RNF213 was identified in 95% of familial patients with moyamoya disease and 79% of sporadic cases, and patients having this polymorphism were found to have significantly earlier disease onset and a more severe form of moyamoya disease, such as the presentation of cerebral infarction and posterior cerebral artery stenosis. The exact mechanism by which the RNF213 abnormality relates to moyamoya disease remains unknown, while recent reports using genetically engineered mice lacking RNF213 by homologous recombination provide new insight for the pathogenesis of this rare entity. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery. More recently, blockade of these pro-inflammatory molecules during perioperative period is attempted to reduce the potential risk of surgical complication including cerebral hyperperfusion syndrome. In this review article, we focus on the genetics and biomarkers of moyamoya disease, and sought to discuss their clinical implication.

  78. 脳動脈瘤塞栓術 困難な動脈瘤への挑戦 ステント支援瘤内塞栓術の効果と限界 中期転帰に見るワイドネック動脈瘤治療の現状

    近藤 竜史, 松本 康史, 鈴木 一郎, 新妻 邦泰, 遠藤 英徳, 藤原 悟, 高橋 明, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 7 (6) 143-143 2013/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

  79. 破裂瘤の治療後早期に破裂した前交通動脈瘤の1例 血行力学的変化の検討

    新妻 邦泰, 杉山 慎一郎, 遠藤 英徳, 鈴木 一郎, 近藤 竜史, 松本 康史, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 7 (6) 266-266 2013/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

    eISSN:2186-2494

  80. Entryのみが閉塞して盲端となった巨大な偽腔が塞栓源と考えられた頸動脈解離に対するステント留置術

    河田 幸波, 松本 康史, 近藤 竜史, 鈴木 一郎, 新妻 邦泰, 遠藤 英徳, 藤原 悟, 高橋 明, 冨永 悌二

    JNET: Journal of Neuroendovascular Therapy 7 (6) 357-357 2013/11

    Publisher: (NPO)日本脳神経血管内治療学会

    ISSN:1882-4072

    eISSN:2186-2494

  81. 【くも膜下出血―診断と治療のNew Standards】くも膜下出血をおこすその他の疾患 細菌性脳動脈瘤

    新妻 邦泰, 清水 宏明, 麦倉 俊司, 冨永 悌二

    Clinical Neuroscience 31 (4) 421-423 2013/04

    ISSN:0289-0585

  82. 増大する脳動脈瘤の血行動態解析

    杉山慎一郎, 清水宏明, 遠藤英徳, 新妻邦泰, 近藤竜史, 松本康史, 長嶺義秀, 藤原悟, 冨永悌二

    日本脳ドック学会総会プログラム・抄録集 22nd 2013

  83. CFD解析による脳動脈瘤壁性状の予測

    新妻邦泰, 杉山慎一郎, 遠藤英徳, 清水宏明, 近藤竜史, 松本康史, 長嶺義秀, 藤原悟, 冨永悌二

    日本脳ドック学会総会プログラム・抄録集 22nd 2013

  84. もやもや病に対する頭蓋外内血行再建術前後の吻合部局所CBF変化と過灌流症候群の関連についての検討

    藤村幹, 新妻邦泰, 遠藤英徳, 井上敬, 清水宏明, 冨永悌二

    脳循環代謝 25 (1) 2013

    ISSN:0915-9401

  85. 出血性椎骨動脈解離に対するinternal coil trappingにおける穿通枝温存

    遠藤英徳, 松本康史, 近藤竜史, 鈴木一郎, 新妻邦泰, 佐藤健一, 清水宏明, 高橋明, 藤原悟, 冨永悌二

    Journal of Neuroendovascular Therapy 7 (6) 2013

    ISSN:1882-4072

  86. ワルファリン内服下マウス中大脳動脈閉塞モデルにおける,新規血栓溶解薬SMTP-7の治療効果

    伊藤明, 新妻邦泰, 清水宏明, 藤村幹, 冨永悌二

    脳循環代謝 25 (1) 2013

    ISSN:0915-9401

  87. 難治てんかん重積に対するLevetiracetam大量経管投与

    加藤 量広, 神 一敬, 板橋 尚, 岩崎 真樹, 新妻 邦泰, 増山 祥二, 金子 仁彦, 菊池 昭夫, 小川 諒, 成川 孝一, 鈴木 靖士, 青木 正志, 中里 信和

    臨床神経学 52 (12) 1614-1614 2012/12

    Publisher: (一社)日本神経学会

    ISSN:0009-918X

    eISSN:1882-0654

  88. CFD解析による脳動脈瘤壁硬化病変予測の可能性

    新妻邦泰, 杉山慎一郎, 井上敬, 遠藤英徳, 藤村幹, 佐藤健一, 清水宏明, 高橋明, 冨永悌二

    脳循環代謝 24 (1) 2012

    ISSN:0915-9401

  89. ラットくも膜下出血後のacute brain injuryに対するedaravoneの治療効果

    新妻邦泰, 藤村幹, 遠藤英徳, 清水宏明, CHAN Pak H., 冨永悌二

    脳循環代謝 23 (1) 2011

    ISSN:0915-9401

  90. Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia

    Kuniyasu Niizuma, Hideyuki Yoshioka, Hai Chen, Gab Seok Kim, Joo Eun Jung, Masataka Katsu, Nobuya Okami, Pak H. Chan

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1802 (1) 92-99 2010/01

    Publisher: ELSEVIER SCIENCE BV

    DOI: 10.1016/j.bbadis.2009.09.002  

    ISSN:0925-4439

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    Mitochondria play important roles as the powerhouse of the cell. After cerebral ischemia, mitochondria overproduce reactive oxygen species (ROS), which have been thoroughly studied with the use of superoxide dismutase transgenic or knockout animals. ROS directly damage lipids, proteins, and nucleic acids in the cell. Moreover, ROS activate various molecular signaling pathways. Apoptosis-related signals return to mitochondria, then mitochondria induce cell death through the release of pro-apoptotic proteins such as cytochrome c or apoptosis-inducing factor. Although the mechanisms of cell death after cerebral ischemia remain unclear, mitochondria obviously play a role by activating signaling pathways through ROS production and by regulating mitochondria-dependent apoptosis pathways. (C) 2009 Elsevier B.V. All rights reserved.

  91. Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival

    Kuniyasu Niizuma, Hidenori Endo, Pak H. Chan

    JOURNAL OF NEUROCHEMISTRY 109 (Suppl 1) 133-138 2009/05

    Publisher: WILEY-BLACKWELL PUBLISHING, INC

    DOI: 10.1111/j.1471-4159.2009.05897.x  

    ISSN:0022-3042

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    Mitochondria are the powerhouse of the cell. Their primary physiological function is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Reactive oxygen species generated from mitochondria have been implicated in acute brain injuries such as stroke and neurodegeneration. Recent studies have shown that mitochondrially-formed oxidants are mediators of molecular signaling, which is implicated in the mitochondria-dependent apoptotic pathway that involves pro- and antiapoptotic protein binding, the release of cytochrome c, and transcription-independent p53 signaling, leading to neuronal death. Oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves phosphatidylinositol 3-kinase/Akt and downstream signaling, which lead to neuronal survival. Genetically modified mice or rats that over-express or are deficient in superoxide dismutase have provided strong evidence in support of the role of mitochondrial dysfunction and oxidative stress as determinants of neuronal death/survival after stroke and neurodegeneration.

  92. ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPUMAの役割について

    新妻邦泰, 藤村幹, 遠藤英徳, 斉藤敦志, 清水宏明, チャン パク・フー, 冨永悌二

    脳循環代謝 21 (1) 2009

    ISSN:0915-9401

  93. もやもや病に対するEC-IC bypass術後急性期3D-TOF MRAを用いた症候性過灌流の診断と予測についての検討

    藤村幹, 麦倉俊司, 新妻邦泰, 清水宏明, 冨永悌二

    脳循環代謝 21 (1) 2009

    ISSN:0915-9401

  94. ラット全脳虚血後の遅発性海馬CA1神経細胞死におけるPIDDosomeの役割について

    新妻邦泰, 藤村幹, 遠藤英徳, 斉藤敦志, 清水宏明, CHAN PH, 冨永悌二

    日本脳神経外科学会総会抄録集(CD-ROM) 68th 2009

    ISSN:1347-9040

  95. くも膜下出血におけるT2<sup>*</sup>強調画像異常低信号域の長期的変化

    高田志保美, 井上敬, 新妻邦泰, 清水宏明, 冨永悌二

    日本脳神経外科学会総会抄録集(CD-ROM) 67th 2008

    ISSN:1347-9040

Show all ︎Show first 5

Books and Other Publications 5

  1. Muse Cells: Endogenous Reparative Pluripotent Stem Cells (Advances in Experimental Medicine and Biology 1103)

    NIIZUMA Kuniyasu, BORLONGAN Cesar V, TOMINAGA Teiji

    Springer (Tokyo) 2018/12

    ISBN: 9784431568452

  2. 基礎からよくわかる 実践的CFD(数値流体力学)入門 脳血管編

    新妻 邦泰, 冨永 悌二

    メディカ出版 2017/04/05

    ISBN: 9784840461474

  3. 脳卒中ガイドライン 2015 日本脳卒中学会脳卒中ガイドライン委員会編

    冨永 悌二, 新妻 邦泰, ほか

    協和企画 2015/06/01

    ISBN: 9784877941697

  4. Magnetic Resonance Angiography Basics to Future

    Kuniyasu Niizuma, Hiroaki Shimizu, Teiji Tominaga

    InTech 2012/03/21

    ISBN: 9789535104018

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    doi:10.5772/30536

  5. Animal Models of Acute Neurological Injuries (Contemporary Neuroscience) 2009th Edition

    Kuniyasu Niizuma, Hidenori Endo, Chikako Nito, D. Jeannie Myer, Gab Seok Kim, Teiji Tominaga, Pak H. Chan

    Humana Press Inc., New York 2008/10/03

    ISBN: 9781603271844

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    Editors: Jun Chen, Zao C. Xu, Xiao-Ming Xu, John H. Zhang

Research Projects 36

  1. Development of vascular permeability control method by integration of blood-brain barrier-on-a-chip and measurement-integrated simulation

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2023/04/01 - 2027/03/31

  2. Elucidation of the pathogenesis of moyamoya disease through Endothelial-Smooth Muscle Interaction and RNF213

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2023/04/01 - 2026/03/31

  3. Elucidating the role of tRNA epitranscriptome in Glioma pathology and development of novel therapies

    Rashad Sherif, 遠藤 俊毅, 七谷 圭, 新妻 邦泰, 金森 政之

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  4. Transcranial Whole Brain Imaging by Microwave-induced Thermoacoustics

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2023/04/01 - 2026/03/31

  5. 人工知能を用いたもやもや病における病期進行予測モデルの開発

    遠藤 英徳, 中川 敦寛, 新妻 邦泰, 麦倉 俊司, 杉山 慎一郎, 園部 真也, 植田 琢也, 面高 俊介

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  6. 急性期脳梗塞における免疫血栓を標的とした新規治療法の開発

    坂田 洋之, 新妻 邦泰, 遠藤 英徳, 田代 亮介, 鹿毛 淳史

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

  7. 脳動脈瘤コイル塞栓術後の内皮形成促進:Muse細胞による新しい治療アプローチ

    高橋 佑介, 富樫 俊太郎, 新妻 邦泰, 板東 良雄, 清水 宏明, 阿部 考貢

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 秋田大学

    2023/04/01 - 2026/03/31

  8. MRI・バイオマーカーによる脳循環自動調節能メカニズム解明及びAIによるその評価

    井上 敬, 冨永 悌二, 新妻 邦泰, 園部 真也

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2026/03/31

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    今年度は、まずバイオマーカーによる神経損傷程度推定法を検討した。脳主幹動脈閉塞例に対し、急性期血行再建術を施行した症例を対象とした。神経損傷バイオマーカーとしては、研究者らがこれまで報告してきたtRNA由来物を測定した。脳神経損傷程度はこれまでMRI拡散強調像で評価されることが一般的であった。しかし、MRI拡散強調像では、すでに非可逆的な損傷を受けていても、所見として捉えることができない偽陰性症例や、その逆に可逆的損傷にもかかわらず、所見が出現する偽陽性の症例が存在する。本研究では、拡散強調画像を取得するタイミングで採血した血漿からtRNA由来物を定量的に測定した。神経損傷は3ヶ月後の神経学的検査で判定することとした。その結果、tRNA由来物はMRI拡散強調像よりも鋭敏に神経損傷を評価できることが判明した。この結果は現在英文誌に投稿中である。 さらに、AIによる神経機能評価法の基礎的な検討も始めた。AIによるdeep learning はこれまでの統計学的手法では抽出困難な危険因子を同定できる可能性がある。しかし、deep learningでは古典的統計学的手法に比べ、必要症例数が飛躍的に増加する。脳循環予備能推定が本研究の最終目標であるが、本年度はまずは十分な症例数のある疾患でAIによる神経機能評価法を確認した。対象としては慢性硬膜下血腫手術例約200例を対象とした。統計学的手法では術後神経機能回復が遅れる危険因子として、年齢・術前意識レベルなどが抽出された。AIを用いた検討では、これら以外にリハビリテーションの有無が、術後神経機能回復と関係があることが示唆された。統計学的手法ではリハビリテーションの有無は交絡因子とされたが、AIでの検討では独立因子と判定された。今後はさらに症例数を増やすことにより、どちらがより臨床的に有効か研究を続けたい。

  9. 脊髄悪性腫瘍に対する光刺激インプラントデバイスを用いた新規治療法の開発

    遠藤 俊毅, 新妻 邦泰, 田中 徹, 大沢 伸一郎, 中川 敦寛

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的研究(萌芽)

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2022/06/30 - 2025/03/31

  10. 慢性期脊髄損傷に対するMuse細胞を用いた新規治療法の開発

    遠藤 俊毅, 冨永 悌二, Rashad Sherif, 新妻 邦泰, 下田 由輝, 正本 和人, 伊藤 明

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 東北医科薬科大学

    2022/04/01 - 2025/03/31

  11. 血流解剖に基づく未破裂脳動脈瘤分類および新規画像診断システムの提案

    杉山 慎一郎, 新妻 邦泰, 安西 眸, 船本 健一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  12. 男性性機能を改善させる再生医療の開発

    山下 慎一, 川守田 直樹, 新妻 邦泰, 伊藤 明宏, 佐竹 洋平

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  13. Elucidation of moyamoya disease pathophysiology through an interaction of hemodynamics and endothelial cells

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2021/04/05 - 2024/03/31

  14. 血管壁イメージングMRIと瘤内血流のAI解析による脳動脈瘤破裂点の推定

    面高 俊介, 中川 敦寛, 新妻 邦泰, 杉山 慎一郎, 園部 真也, 遠藤 英徳, 船本 健一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2021/04/01 - 2024/03/31

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    本研究では近年明らかになったMRIにおける脳動脈瘤壁の造影効果を破裂点の予測に応用し、さらにCFD (数値流体解析: computational fluid dynamics) 解析及びAI (人工知能: artificial intelligence) 解析を組み合わせることで、従来は主に形態学的特徴から予測していた破裂点をより高い精度で予測する手法を確立する。初年度である当該当年度は後ろ向き研究として主に患者データの収集を行った。画像データ(MRI及び脳血管撮影の3次元データ)を院内放射線サーバーからPCへ移す作業を行った。予定していた約400例分のうち2/3程終了した。移行した画像データを用いて画像解析ソフトを用いた瘤壁造影効果の評価、流体解析ソフトを用いたCFD解析を同時に進めているところである。現在のところ中間結果の段階であるが破裂点の予測にはMRIにおける瘤壁造影効果は非常に有用であるとの結果が得られつつある。すなわちくも膜下血種の患者さんで術前に造影MRIを行うことで事前に破裂点を予測しうるとの結果が得られており今後解析が進むにつれて根拠が増すものと予想される。現在移行している画像データはAI解析にも活用でき、将来的にはAI解析も進めることを視野に入れている。関連する検討として同データベースを用いて切迫破裂例における瘤壁臓絵効果に関する検討を行い論文化(Omodaka S et al. J Neurosurg. 2022)、学会発表 (脳神経外科総会2021, Stroke 2022)を行い、瘤壁造影効果の臨床的意義を示すことができており本研究成果の一部であるとともに本研究を後押しする成果が得られている。

  15. Development of Muse cell therapy for dementia

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2020/04/01 - 2023/03/31

  16. くも膜下出血後早期脳損傷の軽減をめざして:エダラボンのドラッグリポジショニング

    針生 新也, 新妻 邦泰, 遠藤 英徳, 伊藤 明

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    くも膜下出血は日本人に多くみられ、致死率および要介護率がそれぞれ40%または30%の未だに転帰不良の疾患である。その理由として、発症直後から手術治療に至るまでの間にも脳圧亢進や酸化ストレスなどに起因する細胞障害性変化が始まっており、くも膜下出血後早期脳損傷として注目されている。 本研究では脳保護薬であるエダラボンによるくも膜下出血後早期脳損傷の抑制効果を研究することを目的とした。エダラボンはフリーラジカルスカベンジャーとして、急性期の脳梗塞に対してすでに臨床現場で汎用されている薬剤である。 研究第一年度はendovascular perforationによるラットくも膜下出血モデルを作成し、レーザー血流計を用いた出血後の脳血流量低下の観測、エダラボン静脈内投与によるくも膜下出血24時間後の生存率の比較試験を行った。 第二年度は前年に得られたエダラボンの至適濃度の投与を行ったモデルを用いて、エダラボンがもたらす神経機能保護効果と組織学的な細胞障害抑制効果の評価を行うべく研究に取り組んだ。ラットくも膜下出血モデルの脳組織から抽出した蛋白質溶解液を用いて断片化DNAの測定を行い、アポトーシスの評価とした。sham群、vehicle群、エダラボン群について比較した結果、vehicle群に対してエダラボン群で断片化DNAは有意に低値を示し、アポトーシスが抑制されているという結果であった。上記実験に時間を要してしまったために組織染色によるアポトーシスの評価や神経機能の行動評価実施には至らず、遅延が発生した状況であるが、次年度以降に研究を加速させたい。、

  17. S1PR1シグナル制御による脳血液関門保護を介したくも膜下出血の新規治療法開発

    伊藤 明, 新妻 邦泰, 遠藤 英徳

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    全脳卒中で最も予後不良であるくも膜下出血においては有効性を示した治療薬は存在しない。脳血液関門(Blood Brain Barrier, BBB)の機能不全は脳卒中にお ける神経損傷の増悪に関与することが示唆されている。脳血管内皮細胞は治療標的としての潜在性を有するが、BBB機能を制御する内皮細胞シグナル経路の理解 が乏しいことから脳卒中における血管内皮を標的とした新たな治療法の開発が進んでいない。くも膜下出血においても発症早期よりBBB機能が破綻し血管透過性 亢進が進み二次脳損傷をもたらし転帰不良に寄与することが知られている。スフィンゴシン-1-リン酸(S1P)は細胞膜上のS1P受容体(S1PR)を介した内皮機能 のモジュレーターである。脳血管においても血管内皮のS1PR1シグナルがBBBを調整し血管透過性制御に関与することが近年明らかとなっている。 本研究は脳血管内皮細胞でのS1PR1シグナル調整によりくも膜下出血の転帰改善が得られるかどうかを動物実験によって検証することを目的としているが、昨年度は薬物的なS1PR1拮抗により野生型マウスにおいてくも膜下出血の転帰を悪化させることを明らかにし、本年度は血管内皮特異的遺伝子改変マウスを主に用いてその作用機序が血管内皮細胞での S1PR1シグナル拮抗によりもたらされていることを証明した。 今後は、最終段階としてS1PR1刺激薬によるくも膜下出血における治療効果を検証したい。

  18. シロスタゾールを用いたもやもや病における内因性幹細胞賦活と血管新生促進療法の開発

    藤村 幹, 冨永 悌二, 新妻 邦泰, 麦倉 俊司, 坂田 洋之

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    もやもや病は異常血管網発達ならびに代償的な側副血行路を含めた血管新生能を有する原因不明の疾患である。小児や若年成人に好発し、浅側頭動脈・中大脳動脈吻合術(直接血行再建術)や側頭筋を用いた間接血行再建術を含めた外科治療の有効性が確立しているが、重症例に対する治療は未確立である。間接術は脳損傷を伴う重症例にも安全に行うことが可能であるが、間接術単独の場合は血管新生不良例が見られる点が問題である。血管新生能を高める試みがなされているがその効果は限定的であるのが現状である。今回、内因性多能性幹細胞とその活性化に期待が持てる薬剤に着目し、間接術からの血管新生の機序を解明し、その効果を促進する手法を開発することによりもやもや病の治療成績の向上が期待できると着想した。本研究の目的は、もやもや病患者クモ膜における内因性多能性幹細胞の発現と血行再建術後の血管新生の関連を明らかにし、「もやもや病に対するシロスタゾールを用いた内因性多能性幹細胞の賦活と血行再建術効果促進」の概念実証し、臨床レベルでもやもや病手術例に対するシロスタゾールを用いた内因性多能性幹細胞の賦活による血行再建術効果療法を確立することである。 2年度目は、血行再建術を行ったもやもや病患者に由来する検体を用いて、患者クモ膜組織における内因性多能性幹細胞を免疫組織学的に検討した。18例の患者より得られたクモ膜について、多能性幹細胞の複数の指標について免疫組織染色を行ったところ多くの検体において多能性幹細胞マーカー陽性所見を認めた。また術後MRAを行い血管新生の程度と術前脳虚血、RNF213遺伝子異常との関連を検証し有意な結果を得た。もやもや病患者クモ膜において内因性多能性幹細胞が存在すること、RNF213遺伝子変異により血管新生が増幅されることが示唆された。

  19. Analysis of latent imaging findings in healthy subjects with moyamoya disease susceptibility gene RNF213 polymorphism using artificial intelligence

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2020/04/01 - 2023/03/31

  20. Muse cell transplantation for Spinal cord injury

    Toshiki Endo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    In the spinal cord injury model, Muse cells can reach to the injured spinal cord after intravenous administration. Muse cells differentiated into neuronal and neural cells and facilitated nerve fibers preservation and possibly regeneration. We confirmed therapeutic potential of Muse cells for severe subacute spinal cord injury.

  21. エラスチン架橋アミノ酸に着目したもやもや病バイオマーカー診断法の確立

    井上 智夫, 冨永 悌二, 藤村 幹, 新妻 邦泰, 遠藤 英徳, 臼杵 豊展

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 北里大学

    2019/04/01 - 2022/03/31

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    本研究の目的は、臨床医学と有機化学の異分野融合型の学際型研究として、動脈壁の構成成分であるエラスチンの架橋アミノ酸desmosineおよびisodesmosineが、もやもや血管の増勢や脳出血、脳梗塞などの致命的となり得る脳血管イベントの発症を推測可能なバイオマーカーであるという作業仮説を検証し、もやもや病の病態評価に関する簡便かつ高精度な診断法を初めて開発することである。 もやもや病患者ではウイリス動脈輪に内膜線維性肥厚、内弾性板の屈曲、中膜の菲薄化などが認められている。その為、動脈壁中膜の主要成分である弾性線維エラスチンが組織学的に破綻している可能性が示唆されるが、生体内での血液生化学的動態には不明な点が多い。したがって、本研究では血液などの臨床試料中のエラスチン架橋アミノ酸の変動をバイオマーカーとする前例のない、簡便かつ客観的で高精度なもやもや病の病期進行予測モデルを構築できる。 もやもや病患者の体内動態に関する以下の3項目につき、計3年間の研究期間内に明らかにする。(i)もやもや病患者の臨床試料中のdesmosine/isodesmosineの定量分析(1年目)(ii)もやもや病患者組織中のdesmosine/isodesmosineの定量分析(2年目)、(iii)抗体作製に基づくELISA法の開発とバイオマーカー診断法の確立(3年目)。東北大学病院脳神経外科を中心にもやもや病患者48例および健常対照者18例に関する臨床データベースを構築した。これをもとに、分担者である上智大学理工学部臼杵研究室で確立した同位体希釈LC-MS/MS法を利用して、血液中のdesmosineおよびisodesmosineの濃度の定量分析を解析中である。

  22. Development of a new experimental model of chronic cerebral ischemia with vascular endothelial impairment and elucidation of hyperperfusion following vascular reconstruction

    Shimizu Hiroaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Akita University

    2018/04/01 - 2021/03/31

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    A rat model of hyperperfusion after vascular reconstruction on chronic cerebral ischemia was investigated, however, laser speckle flowmetry (LAF) provided unreliable cerebral blood flow results. Proper conditions to bring stable LSF results were then explored and several factors such as body temperature, blood pressure, head fixation, and settled condition of craniotomy site for LSF measurement were found to be important. These conditions were applied to the model, which finally demonstrated hyperperfusion reproducibly.

  23. Muse cell therapy for the cure of epileptogenesis

    Osawa Shin-ichiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2018/04/01 - 2021/03/31

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    Muse cells are naturally pluripotent stem cells that exist in living organisms, and are a promising source of cell therapy because of their characteristics of both safety and tissue repair. There are few reports of cell therapy for epilepsy, and this time we examined the possibility of Muse cell therapy for brain damage in acute seizure model. Photic stimulation using optogenetics induces acute seizure in rodent hippocampus and then Muse cells are administered 2 days after the seizure. 3 weeks later we confirmed cells with human-derived antigens: Muse cells. In the future, behavioral experiments and biochemical evaluations are expected to prove the effect of improving epileptigenicity.

  24. Hemodynamic predictors for the growth of unruptured intracranial aneurysms

    Sugiyama Shinichiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2018/04/01 - 2021/03/31

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    The purpose of this study was to clarify the hemodynamic factors that promotes the growth of unruptured intracranial aneurysms by computational fluid dynamics (CFD) analysis.The results of this study suggested the positive relationship between blood inflow rate and aneurysmal growth. The local elevation of pressure by blood inflow promoted the growth of aneurysms. Conversely, the prolongation of blood residence time coincided with the calcification associated with the atherosclerotic changes on aneurysmal wall.

  25. Platform for regenerative therapy of central nervous system using Muse cells

    TOMINAGA TEIJI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

    Category: Grant-in-Aid for Scientific Research (A)

    Institution: Tohoku University

    2017/04/01 - 2020/03/31

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    Cerebral infarction accounts for ~60% of the total stroke and the number of patients is increasing. Even with the current sophisticated treatments including thrombolysis and thrombectomy, more than half patients get disabled. Therefore, it is imperative to develop a new treatment to enhance recovery and restore the lost neurological functions. Multilineage-differentiating stress-enduring (Muse) cells are endogenous nontumorigenic stem cells with pluripotency and minimum safety concerns. Muse cells recognize the injured site, home preferentially into the tissue and spontaneously differentiate into tissue-compatible cells to replace the lost cells, and repair the tissue, delivering functional and structural regeneration. The purpose of this study is to develop Muse cell therapy for central nervous system disorders. If Muse cell treatment was successfully developed, the social and economic impact is unimaginable.

  26. Development of risk evaluation system of cerebral aneurysms based on the computational fluid dynamics

    NIIZUMA KUNIYASU

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

    Category: Grant-in-Aid for Young Scientists (A)

    Institution: Tohoku University

    2017/04/01 - 2020/03/31

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    The purpose of this study is to establish a theoretical basis for diagnosis and treatment using computational fluid dynamics (CFD) for mainly cerebral aneurysms. Simultaneously, we constructed a case repository with hemorrhagic factors. We analyzed numbers of cerebral aneurysms treated by coil embolization or flow diverter, and revealed the risk factors for the recurrence of the aneurysms. We also investigated the complex hemodynamics of Moyamoya disease using CFD using large eddy simulation technique.

  27. Neo-angiogenesis induction by pluripotent stem cell Muse as a new therapeutic strategy for severer form of moyamoya disease

    Miki Fujimura

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2017/04/01 - 2020/03/31

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    In the laboratory research, we established a reproducible chronic hypoperfusion model using mice and rat, and found significant neo-angiogenesis and the migration of immune cells to the brain surface after indirect pial synangiosis. Using moyamoya disease patients’ sample, we found increased serum levels of sCD163 (M2 macrophage-associated factor) and CXCL5, suggesting the contribution of intrinsic immune reaction in its pathophysiology (Fujimura et al. Brain Res 2018). Finally, we found marked expression of endogenous pluripotent stem cells in the arachnoid membrane of moyamoya disease patients, indicating the possible role of endogenous stem cells in the intrinsic angiogenesis in moyamoya disease (Fujimura et al. submitted).

  28. Reconstruction of Neuronal Circuitry by Muse cell transplantation in lacunar stroke

    Sakata Hiroyuki, TOMINAGA Teiji, DEZAWA Mari, Chan Pak H., WATANABE Mika, FUJIMURA Miki, NAKAGAWA Atsuhiro, NIIZUMA Kuniyasu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

    Category: Grant-in-Aid for Young Scientists (A)

    Institution: Tohoku University

    2015/04/01 - 2018/03/31

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    Multilineage-differentiating stress-enduring (muse) cells, subpopulation of bone marrow-mesenchymal stem cells, are endogenous nontumorigenic stem cells with pluripotency. We transplanted Muse cells into the perilesion brain at 2 weeks after lacunar infarction in immunodeficient mice. Transplantation at the delayed subacute phase showed muse cells differentiated into neural cells, facilitated neural reconstruction, improved functions, and displayed solid safety outcomes over prolonged graft maturation period, indicating their therapeutic potential for lacunar stroke.

  29. Computational fluid dynamics in plaque formation of carotid artery

    Saito Atsushi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2015/04/01 - 2018/03/31

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    We analysed relationship between cerebral aneurysm enlargement and hemodynamic stress with computational fluid dynamics. Enlarged aneurysms had broader area with gap between wall shear stress and oscillatory shear index. The results may contribute to prediction of high risk cerebral aneurysms in advance of radical treatment.

  30. New concept of local chemo- and cell-therapy for spinal cord injury using convection-enhanced drug delivery

    Sugiyama Shinichiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2015/04/01 - 2018/03/31

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    Spinal cord injury has dismal prognosis even in this modern era. Convection-enhanced delivery (CED) is a method for distributing small and large molecules locally in the interstitial space of the spinal cord. Delivering these molecules to the spinal cord is otherwise difficult due to the blood spinal cord barrier. This study revealed that regional infusion of drugs into the spinal cord via CED is a promising strategy for treating spinal cord injury. In addition, we investigated the safety and efficacy of stem cell transplantation (multilineage-differentiating stress enduring cell (Muse cell) transplantation) in spinal cord injury.

  31. 正常から病態へ ~脳動脈瘤の発生に関する多元計算解剖学的アプローチ~

    新妻 邦泰

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 新学術領域研究(研究領域提案型)

    Category: 新学術領域研究(研究領域提案型)

    Institution: 東北大学

    2015/04/01 - 2017/03/31

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    数値流体力学(CFD)に関するデータベースを作成し、その中から安定して解析可能であった内頚動脈瘤の40例を抽出し、動脈瘤を仮想的に消去したうえで、動脈瘤g会生じる部位における血流悪性度と血管脆弱性の関連性を検討した。血管悪性度を定量化するflow abnormality indexに関しては、「なし」、「中等度」、「高度」の3群に分類すると、動脈瘤を仮想消去した部位では、90%以上が中等度もしくは高度の血流悪性度を持つことが示唆された。 現在報告されている動脈瘤発生に関与しうる因子としてはwall shear stressなどが挙げられるが、それと比較しても、本研究で示されたflow abnormality indexはより動脈瘤仮想消去部位で後値を示しており、動脈瘤発生に関するbiomarkerとして活用できる可能性が示唆された。 また、少数例の検討にとどまったものの、血管脆弱度に関しても脳動脈瘤患者において高値を呈する傾向を認め、今後の検証が期待される。 また、CFDをより一般的な解析にするために、gold standardと考えられる脳血管撮影(DSA)から得られるデータと、非侵襲的にデータを収集できるmagnetic resonance angiography (MRA)から得られるデータの比較検証をした。DSAおよびMRAデータを比較すると相関係数0.75と比較的良好な相関を示し、非侵襲的手法で十分なCFDが行える可能性が示唆された。

  32. Multidisciplinary Approach for Arteriovenous Malformation Based on Computational Fluid Dynamics

    Shimizu Hiroaki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Akita University

    2014/04/01 - 2017/03/31

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    Hemodynamics of arteriovenous malformation (AVM) was successfully analyzed using computational fluid dynamics (CFD). Four dimensional magnetic resonance imaging (4D-MRI) was also performed and compared with CFD. Hemodynamic parameters such as wall shear stress and velocity were provide by both CFD and 4D-MRI. However patients who suffered from AVM mostly had severe physical conditions, and it was difficult to create a large database during three years. <BR> On the other hand, the research team developed a new approach for diagnosing the risk factor of the recurrence after coil embolization of cerebral aneurysms. Based on it, a new software to evaluate the risk for coil embolization is under developing. In conclusion, this project became a foundation for the future development of CFD.

  33. Establishment of the stem cell transplantation therapy by MUSE for moyamoya disease

    Miki Fujimura

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    The objective of this study was to establish stem cell transplantation therapy using pluripotent MUSE cells for the patients with moyamoya disease. Mice and rats were subjected to chronic cerebral ischemia and then underwent indirect pial synangiosis, in a consistent situation of indirect bypass for moyamoya disease. Two-staged carotid artery occlusion reproducibly provided chronic hypoperfusion and the development of pial synangiosis by our methods. To obtain more similar condition to moyamoya disease, we alternatively generated genetically-engineered mice of RNF213, a susceptibility gene for moyamoya disease. Spontaneous development of moyamoya disease was not evident in these mice, while RNF213-deficient mice demonstrated decreased ratio of regulatory T cells after immunologic adjuvant administration. Regarding MUSE cell preparation, using MUSE cells were successfully sorted by anti- SSEA-3/CD105 antibodies from cultured mesenchymal stromal cells.

  34. Development of stent to treat vertebral artery dissection: achievement of curability and functional preservation

    ENDO Hidenori, SUGIYAMA Shinichiro, NIIZUMA Kuniyasu, NAKAI Masaaki, NAKAGAWA Atsuhiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    Fifteen cases with ruptured vertebral artery dissection admitted to our institution between 2014 and 2016. All the cases were examined by cerebral angiography, and the anatomical morphological features of the dissected segment were analyzed. Furthermore, computational fluid dynamics (CFD) of the dissected segment was assessed, based on the data obtained from cerebral angiography. We studied the appropriate condition to preserve the perforators arising from the dissected segment using the CFD technique. We created the new design of stent in the computer simulation, however, these stents did not apply to the real clinical situation, because there were too many morphological and anatomical variations of the dissected segment.

  35. Brain protection by local hypothermia in the acute phase of traumatic brain injury

    Tominaga Teiji, Endo Toshiki, Saito Ryuta, Nakagawa Atsuhiro, Niizuma Kuniyasu, Sugiyama Shinichiro

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2014/04/01 - 2016/03/31

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    The purpose of this study was to develop new methodology for brain protection. We used convection-enhanced delivery (CFD) to inject low-temperature fluid into damaged tissue in the acute phase of traumatic brain injury. First, we developed magnetic resonance method for real-time monitoring of fluid distribution during the continuous CFD injection. Second, we aimed the proof-of-concept study for the effect of local hypothermia on the damaged brain. In the animal models of traumatic brain injury, it was difficult to perfuse damaged brain tissue with cooling saline because of the rapid elevation of intracranial pressure just after the injury. Though hyperosmotic fluid was reported to be effective in the CFD injection into damaged brain tissue, we could not reproduce the effectiveness of heyperosmotic fluid in our experimental design. In order to make a breakthrough, we are developing the optimal fluid to perfuse the damaged brain tissue.

  36. Prediction of the wall property and rupture risk of cerebral aneurysms based on the computational fluid dynamics

    Niizuma Kuniyasu, SUGIYAMA SHIN-ICHIRO, NAKAGAWA ATSUHIRO, HAYASE TOSHIYUKI, OHTA MAKOTO, FUNAMOTO KENICHI, ARAFUNE TATSUHIKO, WASHIO TOSHIKATSU

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

    Category: Grant-in-Aid for Young Scientists (A)

    Institution: Tohoku University

    2013/04/01 - 2016/03/31

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    The purpose of this study was to build a large-scale cerebral aneurysm database including computational fluid dynamics (CFD) analysis, and to predict wall property and rupture risk. In the 3 years around 500 cases were included. Based on the database, we reported that the yellowish wall can be predicted by CFD. In addition, we revealed that rupture risk or recanalization after coil embolization could be predicted by CFD. Further analysis based on the database and outpatient clinic system are planned.

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Social Activities 3

  1. ishinomaki

    2019/09/23 - 2019/09/23

  2. 日本脳神経外科学会第77回総会 市民公開講座

    2018/10/11 - 2018/10/11

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    脳卒中とその最新治療についての一般市民に向けた講演(講演題目「最新!脳の再生治療」)

  3. 第23回市民医学講座

    仙台市

    2017/05/24 -

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    脳卒中とその最新治療についての一般市民に向けた講演(講演タイトル「脳卒中の話」)