Details of the Researcher

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 238

  1. Retrospective interviews reveal unawareness of weakness following reversible hemispheric suppression: An exploratory study using selective anesthesia for functional evaluation. International-journal

    Hiroaki Hosokawa, Kazuo Kakinuma, Shin-Ichiro Osawa, Hana Kikuchi, Kazuto Katsuse, Shoko Ota, Erena Kobayashi, Nobuko Kawakami, Marie Oyafuso, Kazushi Ukishiro, Kazutaka Jin, Makoto Ishida, Kuniyasu Niizuma, Hidenori Endo, Nobukazu Nakasato, Kyoko Suzuki

    Cortex; a journal devoted to the study of the nervous system and behavior　190　146-154　2025/07/05

    DOI： 10.1016/j.cortex.2025.06.015 　

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    Unawareness of weakness-defined as an explicit failure to recognize one's own limb paresis after brain damage-has long been considered predominantly linked to right-hemisphere dysfunction, yet its laterality remains controversial. We retrospectively analyzed 86 sessions of Selective Anesthesia for Functional Evaluation (SAFE) conducted in 53 patients with surgical epilepsy. SAFE involves delivering a short-acting anesthetic into a single cortical artery branch, resulting in reversible cortical suppression. Contralateral weakness was defined as a positive Barré sign in the upper limb, corresponding to a Manual Muscle Test score of <3. Following the anesthetic effect, patients were asked whether they had experienced any motor impairment. Explicit unawareness was probed using two standardized questions, followed by a limb-specific inquiry. Interviews were conducted in real-time during 28 infusions and repeated within 30 sec of motor recovery in the remaining 58 sessions. Unawareness occurred in 41 of 52 left-hemisphere infusions (78.8%) and in 26 of 34 right-hemisphere infusions (76.5%). Real-time and immediate post hoc ratings were concordant in 26 of 28 paired assessments (93%). Infusions into the M2-superior division were associated with higher rates of unawareness than those into the M2-inferior division (odds ratio = 2.3, 95% confidence interval: 1.1-5.1). Within this reversible perfusion-suppression model, the frequency of unawareness of weakness was hemispherically balanced, promoting a cautious re-evaluation of the presumed right-hemisphere dominance. SAFE provides a practical tool for isolating transient awareness deficits without structural injury and may help bridge pharmacological and lesion-based approaches to brain-behavior mapping.

  2. Decreased Lactococcus lactis and propionic acid in feces of patients with Moyamoya disease: Possible implications of immune dysregulation. International-journal

    Mayuko Otomo, Ryosuke Tashiro, Hidetaka Tokuno, Atsushi Kanoke, Keita Tominaga, Arata Nagai, Takashi Aikawa, Daisuke Ando, Hiroyuki Sakata, Takeya Sato, Takaaki Abe, Hidenori Endo, Kuniyasu Niizuma, Teiji Tominaga

    Cerebrovascular diseases (Basel, Switzerland)　1-15　2025/03/26

    DOI： 10.1159/000545478 　

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    INTRODUCTION: Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive steno-occlusive lesions in the terminal portion of the internal carotid artery. Despite its unknown etiology, immune dysregulation is regarded as a critical trigger for delineating the pathophysiology of MMD. The gut microbiota produces short-chain fatty (SCFA) and organic acids, influencing immune regulation and vascular remodeling. We aimed to characterize the gut microbiota in patients with MMD. METHODS: Sixteen patients with MMD and sixteen healthy controls were included in this study. We performed 16S rRNA sequencing of fecal samples and analyzed microbiome diversity and composition, and quantified SCFA and organic acid levels using liquid chromatography. RESULTS: There were no significant differences in α- and b-diversities among feces from the MMD patients and controls. However, 16S rRNA sequencing identified defective Lactococcus lactis (0 ± 0 in the MMD patients vs. 0.026 ± 0.084 in healthy controls, p = 0.0181) and abundant Gordinobacter pamelaeae (0.030±0.039 in the patients vs. 0.001±0.005 in healthy controls, p = 0.003) are strongly linked to MMD. Propionic acid levels were significantly lower in feces of the MMD patients compared to healthy controls (0.83 ± 0.34 mg/g in the MMD patients vs. 1.20 ± 0.55 mg/g in healthy controls, p = 0.028). CONCLUSION: Decreased Lactococcus lactis can result in reduced lactic acid and propionic acid levels in the feces of the patients. This imbalance in the gut microbiome and SCFA/organic acid levels could contribute to immune dysregulation underlying the vascular remodeling seen in MMD.

  3. Multilineage-differentiating stress-enduring cells attenuate the cognitive impairment caused by chronic cerebral hypoperfusion in rats. International-journal

    Naoya Iwabuchi, Hiroki Uchida, Takatsugu Abe, Takumi Kajitani, Daiki Aburakawa, Ahmed Mansour, Hidenori Endo, Teiji Tominaga, Kuniyasu Niizuma

    Experimental neurology　387　115185-115185　2025/02/12

    DOI： 10.1016/j.expneurol.2025.115185 　

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    Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent- like stem cells that can migrate to damaged sites and contribute to tissue repair. Chronic cerebral hypoperfusion (CCH), which mimics vascular dementia, causes hippocampal neuronal degeneration and white matter (WM) damage, which lead to cognitive dysfunction. Currently, there are no effective treatments for it. We evaluated the efficiency of the human-Muse cell-based product CL2020 in treating CCH in rats. A bilateral common carotid artery occlusion was used to induce cognitive dysfunction. Six-weeks after carotid artery occlusion, CL2020 were injected intravenously. Cognitive function was assessed using a Barnes circular maze (BCM) at 3 weeks after CL2020 administration. Histological findings and western blots were assessed at 4 weeks after CL2020 administration. BCM assessment indicated recovery in cognitive function in the CL2020-treated group. Compared with the vehicle, CL2020 targeted the hippocampus, where it decreased neuronal loss and WM damage. CL2020 also promoted angiogenesis and suppressed apoptotic cell death. Western blotting of hippocampal samples revealed the downregulation of pro- apoptotic and the upregulation of anti-apoptotic proteins in the CL2020-treated group. In conclusion, intravenous administration of CL2020 improved the cognitive deficits caused by CCH, partly because of decreased hippocampal neuronal loss and WM damage, and increased angiogenesis in the hippocampus.

  4. Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation. International-journal

    Yuan Zhou, Sherif Rashad, Kuniyasu Niizuma

    The FEBS journal　292　(8)　2051-2070　2025/01/24

    DOI： 10.1111/febs.17408 　

    ISSN： 1742-464X

    eISSN： 1742-4658

  5. Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation. International-journal

    Daisuke Ando, Sherif Rashad, Thomas J Begley, Hidenori Endo, Masashi Aoki, Peter C Dedon, Kuniyasu Niizuma

    International journal of molecular sciences　26　(2)　2025/01/15

    DOI： 10.3390/ijms26020706 　

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    The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues. Our analysis revealed distinct enrichment patterns of tRNA modifications in different tissues. Queuosine (Q) tRNA modification was most enriched in the brain compared to other tissues, while mitochondrial tRNA modifications and tRNA expression were highest in the heart. Using this observation, we synthesized, and delivered in vivo, codon-mutated EGFP for Q-codons, where the C-ending Q-codons were replaced with U-ending codons. The protein levels of mutant EGFP were downregulated in liver, which is poor in Q, while in brain EGFP, levels did not change. These data show that understanding tRNA modification enrichments across tissues is not only essential for understanding codon decoding and bias but can also be utilized for optimizing gene and mRNA therapeutics to be more tissue-, cell-, or condition-specific.

  6. Publisher Correction: High-throughput fluorescence lifetime imaging flow cytometry. International-journal

    Hiroshi Kanno, Kotaro Hiramatsu, Hideharu Mikami, Atsushi Nakayashiki, Shota Yamashita, Arata Nagai, Kohki Okabe, Fan Li, Fei Yin, Keita Tominaga, Omer Faruk Bicer, Ryohei Noma, Bahareh Kiani, Olga Efa, Martin Büscher, Tetsuichi Wazawa, Masahiro Sonoshita, Hirofumi Shintaku, Takeharu Nagai, Sigurd Braun, Jessica P Houston, Sherif Rashad, Kuniyasu Niizuma, Keisuke Goda

    Nature communications　16　(1)　582-582　2025/01/10

    DOI： 10.1038/s41467-025-55961-4 　

  7. Mechanical thrombectomy for cerebral embolism due to cardiac papillary fibroelastoma: A case report. International-journal

    Kentaro Izumi, Youhei Takeuchi, Naoya Iwabuchi, Masahiro Yoshida, Kuniyasu Niizuma, Hidenori Endo

    Surgical neurology international　16　141-141　2025

    DOI： 10.25259/SNI_68_2025 　

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    BACKGROUND: Papillary fibroelastoma (PFE) and myxoma are relatively common types of benign cardiac tumors. PFE and myxoma can be associated with fatal embolic events. However, PFE is not widely recognized within the field of cerebrovascular diseases. CASE DESCRIPTION: A 54-year-old male presented with a sudden onset of left hemiparesis. Three-dimensional computed tomography (CT) angiography revealed incomplete occlusion of the right middle cerebral artery. Thrombolytic therapy with recombinant tissue-type plasminogen activator was performed, followed by mechanical thrombectomy. Reperfusion was achieved within 199 minutes, resulting in thrombolysis in cerebral infarction grade 2b. The retrieved emboli appeared as a white gelatinous substance, which was diagnosed as PFE by histopathological examination. Transesophageal echocardiography and cardiac CT identified a 6-mm mobile mass in the left atrium. PFE in the left atrium was considered to be the source of the embolism and tumor resection was performed on day 18. Histopathological findings of the resected tumor were identical to those of the emboli. The patient was transferred to a rehabilitation facility on day 36, with a modified Rankin Scale score of 2. CONCLUSION: PFE and myxoma share many clinical features, but PFE tends to be smaller, so detection is more challenging and has likely resulted in under-recognition. PFE and myxoma can be associated with fatal embolic events. Resection is recommended for left-sided, mobile, symptomatic tumors larger than 10 mm. The differential diagnosis of embolus retrieved through mechanical thrombectomy should consider both myxoma and PFE and persistent efforts should be made to detect the embolic origin.

  8. A Case of Partially Thrombosed Dissecting Giant Aneurysm in the Distal Middle Cerebral Artery Treated by Endovascular Parent Artery Occlusion.

    Youhei Takeuchi, Masahiro Yoshida, Yasuo Nishijima, Kuniyasu Niizuma, Hidenori Endo

    NMC case report journal　12　167-173　2025

    DOI： 10.2176/jns-nmc.2024-0252 　

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    Partially thrombosed and dissecting giant peripheral aneurysms present significant challenges for treatment with both direct surgical and endovascular approaches. We report a case of partially thrombosed, dissecting giant aneurysm in the peripheral segment of the middle cerebral artery treated with straightforward endovascular parent artery occlusion without saccular packing. A 30-year-old male presented with sudden loss of consciousness and subarachnoid hemorrhage and was transferred to our hospital. On admission, his level of consciousness was assessed as Japan Coma Scale 100 and Glasgow Coma Scale 8 (E1V2M5), with severe paralysis of the right upper and lower limbs. Computed tomography and magnetic resonance imaging demonstrated a partially thrombosed middle cerebral artery aneurysm with a maximum diameter of 31 mm at the M2 non-branching segment of the left middle cerebral artery mid-trunk. Cerebral angiography indicated potential collateral circulation, no retrograde opacification of the aneurysm, and absence of perforating branches near the lesion, so we selected endovascular parent artery occlusion that targeted only the proximal portion of the aneurysm. Postoperative care focused on managing intracranial pressure and overall systemic management. The patient recovered without significant infarction and was discharged home with a modified Rankin Scale score of 1 4 months after the onset. In general, peripheral aneurysms are less likely to cause perforator infarcts, and larger aneurysms are more tolerant of parent artery occlusion. Therefore, simple endovascular parent artery occlusion targeting only the proximal portion of the aneurysm offers both anatomical and pathophysiological advantages and provides a viable option when direct surgery is challenging.

  9. Multifactorial Assessment of Complication Risks in Embolization for Ruptured Cerebral Aneurysm

    Arata Nagai, Shinya Sonobe, Kuniyasu Niizuma, Tetsuo Ishikawa, Eiryo Kawakami, Yasushi Matsumoto, Hirotoshi Imamura, Tetsu Satow, Koji Iihara, Chiaki Sakai, Nobuyuki Sakai, Shigeru Miyachi, Hidenori Endo, Teiji Tominaga

    Journal of Neuroendovascular Therapy　19　(1)　n/a-n/a　2025

    Publisher: The Japanese Society for Neuroendovascular Therapy

    DOI： 10.5797/jnet.oa.2024-0095 　

    ISSN： 1882-4072

    eISSN： 2186-2494

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    OBJECTIVE: Complications in neuroendovascular therapy for cerebral aneurysm (AN) affect the clinical course of patients. Patient conditions, operating procedures, and operator expertise were highlighted as risk factors for complications. These risk factors often combine and constitute particularly strong risks, resulting in a worsened clinical course. In this study, we performed a multifactorial assessment of complication risks in neuroendovascular therapy. METHODS: We analyzed patient data from the Japanese Registry of NeuroEndovascular Therapy 3, which is a nationwide retrospective cohort study of neuroendovascular procedures conducted between 2010 and 2014. Patients who underwent coil embolization for a ruptured anterior communicating artery (Acom) AN, an internal carotid artery-posterior communicating artery (IC-PC) AN, or basilar artery bifurcation (BA-bif) AN were included in this analysis. Information on 16 explanatory variables and 1 objective variable for each patient was obtained from the dataset as nominal variables. The explanatory variables consisted of patient factors, procedural factors, and an operator factor. The objective variable was whether the following complications occurred: intraprocedural bleeding, postprocedural bleeding, and procedure-related infarction. The specific situations involving multiple risk factors associated with high complication rates were identified using a programmed method. The impact of the absence of a supervising physician was also assessed. RESULTS: A total of 2971 patients were analyzed. The complication rates for patients with Acom ANs, IC-PC ANs, and BA-bif ANs were 12.9%, 10.2%, and 13.7%, respectively. A total of 15 specific situations were identified as follows: 3 related to an Acom AN, with complication rates ranging from 19.3% to 20.3%; 4 related to an IC-PC AN, with complication rates ranging from 15.6% to 17.9%; and 8 related to a BA-bif AN, with complication rates ranging from 20.6% to 33.3%. In 4 of these situations, the absence of a supervising physician significantly impacted complication rates. For instance, the complication rate for patients with IC-PC AN treated under local anesthesia was 16.0% overall, but it was 23.8% without supervising physicians. CONCLUSION: Multifactorial assessment based on patient, procedural, and operator factors provides more reliable risk estimations and will help improve the clinical course.

  10. Fabrication and evaluation of Wrap Around Neural-Pass to record and stimulate neural activity in the cervical spinal cord

    Kazushi Tsuji, Atsuhiko Ninomiya, Naoki Iwanuma, Chenxi Qiu, Shutaro Oba, Hisashi Kino, Takafumi Fukushima, Norihiro Katayama, Kuniyasu Niizuma, Hidenori Endo, Tetsu Tanaka

    Japanese Journal of Applied Physics, Part 1: Regular Papers and Short Notes and Review Papers　63　(12)　2024/12/02

    DOI： 10.35848/1347-4065/ad9a6f 　

    ISSN： 0021-4922

    eISSN： 1347-4065

  11. Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A. International-journal

    Yuan Zhou, Sherif Rashad, Daisuke Ando, Yuki Kobayashi, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cellular physiology　240　(1)　e31477　2024/11/08

    DOI： 10.1002/jcp.31477 　

    ISSN： 0021-9541

    eISSN： 1097-4652

  12. Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke. International-journal

    Kuniyasu Niizuma, Naoko Nishimura, Keiko Hasegawa, Takashi Moritoyo, Kohsuke Kudo, Josh Bell, Michael Wald, Yoshifumi Umeda, Kazuhiko Kuribayashi, Yasuo Toda, Teiji Tominaga, Keiji Hasumi

    Stroke　55　(12)　2786-2794　2024/11/07

    DOI： 10.1161/STROKEAHA.124.048464 　

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    BACKGROUND: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence). RESULTS: Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P=0.03). CONCLUSIONS: JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent. REGISTRATION: URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.

  13. 麻酔薬の頭蓋内選択的動注と認知神経学的評価を融合した任意脳領域の機能局在診断法

    大沢 伸一郎, 鈴木 匡子, 柿沼 一雄, 勝瀬 一登, 浮城 一司, 金森 政之, 下田 由輝, 新妻 邦泰, 松本 康史, 神 一敬, 中里 信和, 遠藤 英徳

    日本脳神経血管内治療学会学術集会抄録集　40回　330-330　2024/11

    Publisher: (一社)日本脳神経血管内治療学会

    eISSN： 2759-6907

  14. High-throughput optical imaging technology for large-scale single-cell analysis of live Euglena gracilis Peer-reviewed

    Cheng Lei, Yuta Nakagawa, Yuzuki Nagasaka, Tianben Ding, Hiroshi Kanno, Chihana Toyokawa, Kuniyasu Niizuma, Kengo Suzuki, Ming Li, Anwar Sunna, Vladimir Hampl, Keisuke Goda

    TrAC Trends in Analytical Chemistry　180　117938-117938　2024/11

    Publisher: Elsevier BV

    DOI： 10.1016/j.trac.2024.117938 　

    ISSN： 0165-9936

  15. Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen. International-journal

    Yuya Kato, Daiki Aburakawa, Ryosuke Tashiro, Yuan Zhou, Sherif Rashad, Hidenori Endo, Teiji Tominaga, Kuniyasu Niizuma

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism　45　(3)　271678X241290363-557　2024/10/13

    DOI： 10.1177/0271678X241290363 　

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    Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.

  16. Levodopa-resistant parkinsonism developing after ventriculoperitoneal shunting for obstructive hydrocephalus and improving after endoscopic third ventriculostomy, with specific consideration of brainstem morphology: illustrative case. International-journal

    Yoshihiko Morisue, Shin-Ichiro Osawa, Kuniyasu Niizuma, Shigenori Kanno, Kyoko Suzuki, Hidenori Endo

    Journal of neurosurgery. Case lessons　8　(11)　2024/09/09

    DOI： 10.3171/CASE2429 　

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    BACKGROUND: Parkinsonism has been reported in patients with obstructive hydrocephalus (OH) following ventriculoperitoneal shunting (VPS). While levodopa works well, some cases are drug resistant. A few case series have reported that endoscopic third ventriculostomy (ETV) is beneficial, though its mechanism remains unclear. The use of a pathophysiology-reflected marker can aid in the diagnosis and treatment strategy. The authors report a case of parkinsonism due to OH after VPS that improved after ETV in a patient taking levodopa, which was subsequently discontinued. OBSERVATIONS: A 52-year-old man who had undergone VPS for OH caused by aqueductal stenosis with a tectal tumor presented with severe consciousness disturbance due to acute hydrocephalus and levodopa-refractory parkinsonism after multiple episodes of shunt malfunction. Magnetic resonance imaging showed an elevation of the floor of the third ventricle. ETV was performed to stabilize the pressure imbalance across the stenosis, and his parkinsonism symptoms improved after long-term rehabilitation, resulting in levodopa discontinuation. His pontomesencephalic angle, the angle between the anterior surface of the midbrain and upper surface of the pons in the midline of the sagittal plane, was significantly decreased. LESSONS: The focus in such cases should be on the essence of the pathophysiology for improving the symptoms rather than on easy-to-understand indicators such as ventricle size. https://thejns.org/doi/10.3171/CASE2429.

  17. High-throughput fluorescence lifetime imaging flow cytometry. International-journal

    Hiroshi Kanno, Kotaro Hiramatsu, Hideharu Mikami, Atsushi Nakayashiki, Shota Yamashita, Arata Nagai, Kohki Okabe, Fan Li, Fei Yin, Keita Tominaga, Omer Faruk Bicer, Ryohei Noma, Bahareh Kiani, Olga Efa, Martin Büscher, Tetsuichi Wazawa, Masahiro Sonoshita, Hirofumi Shintaku, Takeharu Nagai, Sigurd Braun, Jessica P Houston, Sherif Rashad, Kuniyasu Niizuma, Keisuke Goda

    Nature communications　15　(1)　7376-7376　2024/09/04

    DOI： 10.1038/s41467-024-51125-y 　

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    Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.

  18. 後大脳動脈で灌流される海馬周囲構造への超選択的麻酔は記憶機能のモダリティ別評価を可能にする

    大沢 伸一郎, 鈴木 匡子, 柿沼 一雄, 勝瀬 一登, 菊地 花, 浮城 一司, 石田 誠, 下田 由輝, 新妻 邦泰, 神 一敬, 中里 信和, 遠藤 英徳

    てんかん研究　42　(2)　514-514　2024/09

    Publisher: (一社)日本てんかん学会

    ISSN： 0912-0890

    eISSN： 1347-5509

  19. Aneurysm Wall Enhancement Can Predict Rupture Point in Intracranial Aneurysms With Multiple Blebs. International-journal

    Shunsuke Omodaka, Shin-Ichiro Sugiyama, Hiroyuki Sakata, Kenichi Funamoto, Takuhiro Yamaguchi, Kuniyasu Niizuma, Hidenori Endo

    Neurosurgery　96　(3)　593-599　2024/08/08

    DOI： 10.1227/neu.0000000000003134 　

    ISSN： 0148-396X

    eISSN： 1524-4040

  20. Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit. International-journal

    Shin-Ichiro Osawa, Kyoko Suzuki, Kazushi Ukishiro, Kazuo Kakinuma, Makoto Ishida, Kuniyasu Niizuma, Yoshiteru Shimoda, Hana Kikuchi, Ryuzaburo Kochi, Kazutaka Jin, Yasushi Matsumoto, Mitsugu Uematsu, Nobukazu Nakasato, Hidenori Endo, Teiji Tominaga

    Cortex; a journal devoted to the study of the nervous system and behavior　176　209-220　2024/05/19

    DOI： 10.1016/j.cortex.2024.04.016 　

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    INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

  21. たこつぼ型心筋症を併発したくも膜下出血に安全にクラゾセンタンを投与した1例

    佐藤 吉通, 西嶌 泰生, 熊井 萌, 新妻 邦泰, 吉田 昌弘, 遠藤 英徳

    脳卒中の外科　52　(3)　231-236　2024/05

    Publisher: (一社)日本脳卒中の外科学会

    ISSN： 0914-5508

    eISSN： 1880-4683

  22. Author Correction: 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　2024/04/02

    DOI： 10.1038/s41551-024-01200-y 　

  23. Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment. International-journal

    Shinya Minatoguchi, Yasuyuki Fujita, Kuniyasu Niizuma, Teiji Tominaga, Toru Yamashita, Koji Abe, Mari Dezawa

    Stem cells translational medicine　13　(6)　532-545　2024/04/01

    DOI： 10.1093/stcltm/szae018 　

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    The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. A Case of Hanging with Limited Specific Postmortem Brain Imaging.

    Arata Nagai, Tomoya Kobayashi, Kyuzo Kurosawa, Kuniyasu Niizuma, Hidenori Endo

    NMC case report journal　11　249-255　2024

    DOI： 10.2176/jns-nmc.2024-0113 　

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    In Japan, the number of autopsies has steadily decreased. Therefore, postmortem imaging methods have positioned as valuable supplemental or complementary tools in autopsy procedures. We clinicians are increasingly faced with the need to infer cause of death from postmortem imaging findings. We report computed tomography (CT) and magnetic resonance imaging (MRI) findings of a 41-year-old man who committed suicide by hanging. CT revealed fractures of the left superior horn of the thyroid cartilage. Head MRI showed high signal intensity in the basal ganglia on the T1-weighted image and high-intensity rims along the cerebral cortex on the diffusion-weighted image; however, these were considered normal postmortem changes. There were no significant findings in the heart, major blood vessels, or abdominal organs. The contents of the stomach were minimal, and no tablets or other evidence suggestive of drug overdose were identified. Traumatic changes were not observed. Based on the scene and his circumstances, it was speculated that he died by hanging and an autopsy was not performed. This case highlights the importance of understanding normal postmortem brain imaging changes to estimate the true cause of death.

  30. 産学連携における最新の動向

    中川 敦寛, Leor Perl, John Lee, 原田 成美, 大田 千晴, 志賀 卓弥, 角南 沙己, 新妻 邦泰, 遠藤 英徳, 張替 秀郎, 冨永 悌二

    Neurological Surgery　52　(1)　213-225　2024/01

    Publisher: (株)医学書院

    ISSN： 0301-2603

    eISSN： 1882-1251

  31. Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study. International-journal

    Hiroyuki Sakata, Atsushi Kanoke, Hiroki Uchida, Shinya Haryu, Shunsuke Omodaka, Naoto Kimura, Masahiro Yoshida, Kuniyasu Niizuma, Teiji Tominaga, Hidenori Endo

    Frontiers in neurology　15　1413632-1413632　2024

    DOI： 10.3389/fneur.2024.1413632 　

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    INTRODUCTION: Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice. METHODS: We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia. RESULTS: The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity. CONCLUSION: A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.

  32. Endovascular Treatment of Wide-Neck Bifurcation Aneurysm: Recent Trends in Coil Embolization with Adjunctive Technique.

    Shinya Haryu, Hiroyuki Sakata, Yasushi Matsumoto, Kuniyasu Niizuma, Hidenori Endo

    Journal of neuroendovascular therapy　18　(3)　75-83　2024

    DOI： 10.5797/jnet.ra.2023-0072 　

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    Wide-neck bifurcation aneurysms (WNBAs) are sometimes challenging to treat. During endovascular treatment, it is important to prevent coil deviation and preserve normal vessels. Adjunctive balloon- and stent-assisted techniques have been developed. A meta-analysis of endovascular treatments of WNBAs revealed that only 40% of patients had complete occlusion. Recently, novel devices have been developed to expand the range of treatment options. Flow-diverter stents and intra-aneurysmal flow disruption devices do not require coils; however, coil embolization remains the standard procedure used by many neurointerventionists. This review describes the recent trends in adjunctive techniques for supporting coil embolization for WNBAs. We referred to literature on balloon-assisted techniques, stent-assisted techniques, Y-stenting, PulseRider, Barrel stents, Comaneci temporary stents, pCONUS, and eCLIPs. These reports showed that adequate embolization rates were generally greater than 80%, and the complete occlusion rate was as high as 94.6%. All devices had a relatively high occlusion rate; however, it may be inaccurate to simply compare each device because of the heterogeneity of the studies. It is important to select the best treatment for each individual case by considering not only literature-based efficacy and safety but also patient background, aneurysm characteristics, and operator experience.

  33. 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.

  34. 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　133　(3)　332-340　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.

  35. 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.

  36. 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.

  37. 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).

  38. 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.

  39. 【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

  40. 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.

  41. 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.

  42. 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.

  43. 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.

  44. 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.

  45. 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.

  46. 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

  47. 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 　

  48. 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.

  49. 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.

  50. 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.

  51. 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).

  52. 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.

  53. 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.

  54. 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.

  55. 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.

  56. 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.

  57. Case Report: Vertebro-vertebral arteriovenous fistula showing symptoms mimicking ALS: Diagnostic imaging supports accurate differentiation between ALS and mimicking conditions. International-journal

    Hinako Kirikae, Ryuhei Harada, Tatsuhiko Hosaka, Tatsuro Misu, Daisuke Ando, Hitoshi Warita, Toshiki Endo, Shinya Sonobe, Kuniyasu Niizuma, Masashi Aoki

    F1000Research　11　546-546　2022

    DOI： 10.12688/f1000research.121554.3 　

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    We report a rare case of a vertebro-vertebral arteriovenous fistula (VVAVF) manifesting as amyotrophic lateral sclerosis (ALS). A 76-year-old female patient presented with progressive weakness, muscle atrophy, fasciculation, and preserved deep tendon reflexes in the right upper limb. Electrophysiological testing showed lower motor neuron dysfunction. The patient was suspected to have ALS, but cervical magnetic resonance imaging (MRI) revealed enlarged blood vessels in the spinal canal, which compressed the cervical spinal cord and nerve roots. Angiography showed a shunt from the right vertebral artery to the right intervertebral vein and the vertebral venous plexus; therefore, the patient was diagnosed with VVAVF. Transarterial embolization was performed to obliterate the shunt, and weakness in the patient's right upper limb subsequently improved. It is worth considering VVAVF as a differential diagnosis of ALS-like diseases.

  58. 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.

  59. 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.

  60. 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.

  61. 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.

  62. 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.

  63. 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.

  64. 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.

  65. 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.

  66. 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.

  67. 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

  68. 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.

  69. 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.

  70. 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.

  71. 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.

  72. 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.

  73. 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.

  74. 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.

  75. 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.

  76. 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.

  77. 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.

  78. 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.

  79. 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.

  80. 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.

  81. 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.

  82. 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.

  83. 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.

  84. 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.

  85. 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.

  86. 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.

  87. 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.

  88. XGBoostによる機械学習手法を用いた頸髄損傷の予後予測因子の抽出

    井上 智夫, 市川 太祐, 上野 太郎, 井上 敬, 遠藤 俊毅, 鈴木 晋介, 上之原 広司, 新妻 邦泰, 冨永 悌二

    Journal of Spine Research　11　(3)　115-115　2020/03

    Publisher: (一社)日本脊椎脊髄病学会

    ISSN： 1884-7137

    eISSN： 2435-1563

  89. 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.

  90. 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.

  91. 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.

  92. 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.

  93. 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

  94. 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.

  95. 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.

  96. 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.

  97. 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.

  98. 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.

  99. 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.

  100. 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

  101. 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.

  102. 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.

  103. 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.

  104. 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.

  105. 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.

  106. 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

  107. 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

  108. 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.

  109. 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.

  110. 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 　

  111. 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.

  112. 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

  113. 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

  114. 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.

  115. 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.

  116. 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.

  117. 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.

  118. 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.

  119. 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.

  120. [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

  121. 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.

  122. 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

  123. 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.

  124. 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

  125. 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

  126. 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

  127. 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

  128. 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

  129. 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.

  130. 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

  131. 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

  132. 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

  133. 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

  134. 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

    DOI： 10.1016/j.clineuro.2017.09.005 　

    ISSN： 0303-8467

    eISSN： 1872-6968

  135. 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

    DOI： 10.1007/s10143-017-0868-2 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  136. 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

    DOI： 10.1016/j.jstrokecerebrovasdis.2017.06.032 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  137. 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

  138. 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

    DOI： 10.1007/s10143-017-0866-4 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  139. 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

    DOI： 10.1007/s10143-017-0845-9 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  140. 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 　

  141. 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

    DOI： 10.1007/s00701-017-3112-5 　

    ISSN： 0001-6268

    eISSN： 0942-0940

  142. 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

    DOI： 10.3171/2016.2.JNS152370 　

    ISSN： 0022-3085

    eISSN： 1933-0693

  143. 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

    DOI： 10.1161/STROKEAHA.116.014950 　

    ISSN： 0039-2499

    eISSN： 1524-4628

  144. 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>

  145. 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>

  146. 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 　

  147. 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

  148. 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

    DOI： 10.1016/j.jstrokecerebrovasdis.2016.09.035 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  149. 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

    DOI： 10.1016/j.wneu.2016.09.040 　

    ISSN： 1878-8750

    eISSN： 1878-8769

  150. 再生医療の基礎と臨床UP to DATE Muse細胞による脳梗塞治療

    新妻 邦泰, 坂田 洋之, 内田 浩喜, 森田 隆弘, 阿部 考貢, 藤村 幹, 出澤 真理, 冨永 悌二

    脳循環代謝　28　(1)　127-127　2016/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  151. 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

    DOI： 10.1161/STROKEAHA.116.013555 　

    ISSN： 0039-2499

    eISSN： 1524-4628

  152. 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

    DOI： 10.1016/j.jstrokecerebrovasdis.2016.07.042 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  153. 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

    DOI： 10.1007/s10143-016-0734-7 　

    ISSN： 0344-5607

    eISSN： 1437-2320

  154. 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

    DOI： 10.1016/j.clineuro.2016.07.013 　

    ISSN： 0303-8467

    eISSN： 1872-6968

  155. 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

    DOI： 10.3174/ajnr.A4722 　

    ISSN： 0195-6108

    eISSN： 1936-959X

  156. 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

    DOI： 10.1016/j.brainres.2016.03.009 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  157. 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

  158. 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

    DOI： 10.1016/j.brainres.2015.10.055 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  159. 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

    DOI： 10.1002/stem.2206 　

    ISSN： 1066-5099

    eISSN： 1549-4918

  160. 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 　

    More details Close

    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.

  161. 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

    DOI： 10.1155/2016/2386031 　

    ISSN： 1748-670X

    eISSN： 1748-6718

  162. 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

    DOI： 10.1016/j.clineuro.2015.10.029 　

    ISSN： 0303-8467

    eISSN： 1872-6968

  163. 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 　

  164. 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

    DOI： 10.1016/j.brainres.2015.10.039 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  165. 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

    DOI： 10.1371/journal.pone.0143756 　

    ISSN： 1932-6203

  166. 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

    DOI： 10.1016/j.jstrokecerebrovasdis.2015.06.028 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  167. 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

    DOI： 10.1016/j.brainres.2015.07.039 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  168. 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

  169. 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

    DOI： 10.1227/NEU.0000000000000867 　

    ISSN： 2332-4252

  170. 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

    DOI： 10.2176/nmc.cr.2015-0052 　

    ISSN： 0470-8105

    eISSN： 1349-8029

  171. 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

    DOI： 10.1016/j.jstrokecerebrovasdis.2015.04.031 　

    ISSN： 1052-3057

    eISSN： 1532-8511

  172. 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

    DOI： 10.3171/2014.9.JNS14778 　

    ISSN： 0022-3085

    eISSN： 1933-0693

  173. 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 　

  174. 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:

    DOI： 10.2335/scs.43.136 　

    ISSN： 0914-5508

    eISSN： 1880-4683

  175. 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

    DOI： 10.1179/1743132814Y.0000000432 　

    ISSN： 0161-6412

    eISSN： 1743-1328

  176. 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

    DOI： 10.1016/j.brainres.2014.11.014 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  177. 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:

    ISSN： 1880-9278

  178. 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

    DOI： 10.1097/WNR.0000000000000289 　

    ISSN： 0959-4965

    eISSN： 1473-558X

  179. 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

    DOI： 10.2176/nmc.tn.2014-0202 　

    ISSN： 0470-8105

    eISSN： 1349-8029

  180. 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 　

  181. 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

    More details Close

    ISBN:0289-8438

  182. 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

    DOI： 10.1016/j.brainres.2014.07.004 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  183. 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

    DOI： 10.3171/2014.3.PEDS13610 　

    ISSN： 1933-0707

    eISSN： 1933-0715

  184. 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

  185. 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

    DOI： 10.1016/j.brainres.2014.01.011 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  186. 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

    DOI： 10.1227/NEU.0000000000000238 　

    ISSN： 0148-396X

    eISSN： 1524-4040

  187. 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

  188. 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

  189. 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

  190. 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

  191. 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

    DOI： 10.1227/NEU.0000000000000189 　

    ISSN： 0148-396X

    eISSN： 1524-4040

  192. 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

  193. 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

  194. 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

    DOI： 10.1227/NEU.0000000000000096 　

    ISSN： 0148-396X

    eISSN： 1524-4040

  195. 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

  196. 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

  197. 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

  198. 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

  199. 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

  200. 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

  201. 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

  202. 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

  203. 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

  204. 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

  205. 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

    DOI： 10.1093/brain/aws259 　

    ISSN： 0006-8950

  206. 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

    DOI： 10.1161/STROKEAHA.112.656900 　

    ISSN： 0039-2499

  207. 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:

    ISSN： 0387-0138

  208. 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

    DOI： 10.1523/JNEUROSCI.5686-11.2012 　

    ISSN： 0270-6474

  209. 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

  210. 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

  211. 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

    DOI： 10.1089/neu.2010.1662 　

    ISSN： 0897-7151

  212. 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

    DOI： 10.2176/nmc.51.275 　

    ISSN： 0470-8105

  213. 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

    DOI： 10.1038/jcbfm.2010.166 　

    ISSN： 0271-678X

  214. 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

    DOI： 10.1002/stem.584 　

    ISSN： 1066-5099

    eISSN： 1549-4918

  215. 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

  216. 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

    DOI： 10.1038/jcbfm.2010.45 　

    ISSN： 0271-678X

  217. 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

    DOI： 10.2176/nmc.50.977 　

    ISSN： 0470-8105

  218. 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

    DOI： 10.1007/s12035-010-8102-z 　

    ISSN： 0893-7648

  219. 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

  220. 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

  221. 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

    DOI： 10.1523/JNEUROSCI.4161-09.2009 　

    ISSN： 0270-6474

  222. 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

    DOI： 10.1161/STROKEAHA.108.524447 　

    ISSN： 0039-2499

  223. 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 　

  224. 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

    DOI： 10.1016/j.jocn.2007.09.024 　

    ISSN： 0967-5868

  225. 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

    DOI： 10.1038/jcbfm.2008.60 　

    ISSN： 0271-678X

  226. 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

    DOI： 10.1073/pnas.0806222105 　

    ISSN： 0027-8424

  227. 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

    DOI： 10.1089/neu.2007.0438 　

    ISSN： 0897-7151

  228. PUMA is involved in acute brain injury after subarachnoid hemorrhage in rats

    Kuniyasu Niizuma, Hidenori Endo, Miki Fujimura, Teiji Tominaga, Pak H. Chan

    Journal of Cerebral Blood Flow and Metabolism　27　(1)　BP55-01　2007/11/13

    ISSN： 0271-678X

  229. Reduction in oxidative stress by SOD1 overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/GSK3b survival signaling

    Hidenori Endo, Kuniyasu Niizuma, Miki Fujimura, Teiji Tominaga, Pak H. Chan

    Journal of Cerebral Blood Flow and Metabolism　27　(1)　BP51-01　2007/11/13

    ISSN： 0271-678X

  230. 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

  231. 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

    DOI： 10.1016/j.jocn.2005.09.021 　

    ISSN： 0967-5868

  232. 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

    DOI： 10.1016/j.jocn.2004.11.025 　

    ISSN： 0967-5868

  233. 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

    DOI： 10.11477/mf.1436100253 　

    ISSN： 0301-2603

  234. 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

  235. 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

  236. 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

  237. 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

  238. 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

    ISSN： 0022-3085

Show all ︎Show first 5

Misc. 103

  1. 脳梗塞に対するMuse細胞治療

    新妻 邦泰

    Journal of Clinical Rehabilitation　33　(6)　556-560　2024/06

    Publisher: 医歯薬出版(株)

    ISSN： 0918-5259

  2. 心房細動に対する完全胸腔鏡下左心耳閉鎖術とハイブリッドアブレーションの可能性と展望

    佐藤宏行, 中野誠, 野田崇, 細山勝寛, 齋木佳克, 新妻邦泰, 遠藤英徳, 安田聡

    日本心臓病学会学術集会(Web)　72nd　2024

  3. 後大脳動脈への超選択的麻酔薬注入による記憶機能のカテゴリ別評価

    大沢伸一郎, 鈴木匡子, 柿沼一雄, 勝頼一登, 菊地花, 浮城一司, 石田誠, 新妻邦泰, 新妻邦泰, 神一敬, 中里信和, 遠藤英徳

    日本ヒト脳機能マッピング学会プログラム・抄録集　26th　2024

  4. Verification for safety and efficacy of hydrogel-based organic electrode by physician-initiated clinical trial

    大沢伸一郎, 新妻邦泰, 中川敦寛, 新妻邦泰, 中川敦寛, 浮城一司, 下田由輝, 神一敬, 植松貢, 岩崎真樹, 西澤松彦, 中里信和, 冨永悌二, 遠藤英徳

    日本てんかん外科学会プログラム・抄録集　47th　2024

  5. 【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

  6. 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 　

    More details Close

    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.

  7. 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

  8. 【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

  9. 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

  10. 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

  11. 【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

  12. 【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

  13. 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

  14. 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

  15. 【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

  16. 【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

  17. 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

  18. 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, 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(Web)　49　(5)　2021

    ISSN： 2188-031X

  19. Provocation test by super-selective infusion of propofol predicts post-surgical functional outcome.

    大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 新妻邦泰, 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(Web)　6　(Supplement)　2021

    ISSN： 2424-1709

  20. 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

  21. 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

  22. 【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

  23. 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

  24. 【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

  25. 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

  26. 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

  27. マウスラクナ梗塞モデルに対するMuse細胞含有製剤CL2020の治療効果の検討

    阿部考貢, 油川大輝, 新妻邦泰, 新妻邦泰, 新妻邦泰, 串田良祐, 若尾昌平, 出澤真理, 冨永悌二

    日本異種移植研究会プログラム・抄録集　22nd (CD-ROM)　2020

  28. 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, 新妻邦泰, 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(Web)　32　(1)　2020

    ISSN： 2188-7519

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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 　

    More details Close

    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.

  35. 【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

  36. 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

  37. 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

  38. 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

  39. 【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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 【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

  47. 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

  48. 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

  49. 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

  50. 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

  51. 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

  52. 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

  53. 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

  54. 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

  55. 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

  56. 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

  57. 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

  58. 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

  59. 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

  60. 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

  61. 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

  62. 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

  63. 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

  64. 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

  65. 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

  66. 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

  67. 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

  68. 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

  69. 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

  70. 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

  71. 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

  72. 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

  73. 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

  74. 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

  75. 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

  76. 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 　

  77. 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

  78. 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

  79. 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

  80. 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

  81. 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

  82. 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

    More details Close

    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 c 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).

  83. 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

  84. 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

  85. 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

    DOI： 10.5853/jos.2014.16.2.65 　

    ISSN： 2287-6391

    eISSN： 2287-6405

  86. 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

  87. 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

  88. 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

  89. 【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

  90. 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

  91. 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

  92. 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

  93. 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

  94. 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

  95. 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

  96. 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

  97. 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

  98. 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

    DOI： 10.1016/j.bbadis.2009.09.002 　

    ISSN： 0925-4439

  99. 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

    DOI： 10.1111/j.1471-4159.2009.05897.x 　

    ISSN： 0022-3042

  100. 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

  101. 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

  102. 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

  103. くも膜下出血におけるT2*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

    More details Close

    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

    More details Close

    Editors: Jun Chen, Zao C. Xu, Xiao-Ming Xu, John H. Zhang

Presentations 64

  1. 脳梗塞に対するMuse細胞治療の開発 Invited

    新妻 邦泰

    第21回泌尿器科再建再生研究会　2024/06/01

  2. 脳血管攣縮のメカニズムと治療：エンドセリンの視点から Invited

    新妻 邦泰

    第44回日本脳神経外科コングレス総会　2024/05/12

  3. Development of Stem Cell Therapy for Cerebral Infarction Invited

    Kuniyasu Niizuma

    Abu Dhabi 2024 International Brain & Spine Congress (ADNEURO 2024)　2024/04/28

  4. Development of Novel Thrombolytic and Neuroprotective Therapies for Acute Cerebral Infraction International-presentation Invited

    Niizuma K

    1st SSMC Anneual Neurosurgery Scientific Day　2024/04/25

  5. SMTPを用いた新規血栓溶解剤の開発と実用化に向けて Invited

    新妻 邦泰

    第49回日本脳卒中学会学術集会　2024/03/07

  6. 脳腫瘍に対する光治療の可能性 Invited

    計算メディカルサイエンス ワークショップ2023　2023/12/11

  7. Development of Muse Cell Therapy for Ischemic Stroke International-presentation

    Kuniyasu Niizuma, Hidenori Endo

    2023/11/26

  8. 中枢神経疾患に対するMuse細胞治療 Invited

    新妻邦泰

    第66回日本脳循環代謝学会学術集会　2023/11/10

  9. 脳梗塞に対するMuse細胞治療 Invited

    新妻邦泰

    第47回日本高次機能障害学会学術総会　2023/10/28

  10. 中枢神経疾患に対するMuse細胞療法の開発 Invited

    新妻邦泰

    日本脳神経外科学会第82回学術総会　2023/10/25

  11. 脳卒中・心臓病等総合支援センターモデル事業に関して Invited

    新妻邦泰

    ストップ！NO卒中プロジェクト支部講演会 in 宮城　2023/10/03

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    日本脳卒中学会認定脳卒中専門医 認定3単位対象講演

  12. 脳梗塞に対するMuse細胞治療の開発

    新妻邦泰

    第5回再生医療とリハビリテーション学会学術大会　2023/09/30

  13. 脳神経外科領域における数理学的手法の活用を目指して

    新妻邦泰

    第4回『医学と数理』研究会　2023/09/29

  14. 脳梗塞に対するMUSE細胞治療 ～基礎から治験まで～ Invited

    新妻邦泰

    第60回日本リハビリテーション医学会学術集会　2023/06/29

  15. SMTPによる新規血栓溶解剤の開発と実用化に向けて

    新妻邦泰

    第64回日本神経学会学術大会　2023/05/31

  16. 再生治療のフロンティア Invited

    新妻邦泰

    第43回日本脳神経外科コングレス総会　2023/05/20

  17. 脳梗塞に対するMuse細胞治療の開発 Invited

    新妻邦泰

    第128回日本解剖学会総会・全国学術集会　2023/03/19

  18. シーズ探索と実用化研究の取り組み Invited

    新妻邦泰

    Stroke2023　2023/03/18

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    合同シンポジウム12 「脳卒中研究の最前線～研究資金獲得と最先端研究の動向～」

  19. 脳梗塞に対するMuse細胞治療 Invited

    新妻邦泰

    第52回日本脳卒中の外科学会学術集会　2023/03/16

  20. Development of stem cell-based therapy for ischemic stroke International-presentation Invited

    Kuniyasu Niizuma, Teiji Tominaga

    The 10th Pan Pacific Neurosurgical Congress　2023/02/07

  21. 脳梗塞亜急性期に対するMuse細胞治療 Invited

    新妻 邦泰

    第52回小児神経学セミナー　2022/12/01

  22. 脳梗塞に対するMuse細胞治療 Invited

    新妻 邦泰, 冨永 悌二

    第65回日本脳循環代謝学会学術集会　2022/10/28

  23. PNAS掲載への道のり Invited

    新妻 邦泰

    日本脳神経外科学会 第81回学術総会　2022/09/28

  24. Development of Muse Cell Therapy for Ischemic Stroke International-presentation Invited

    Niizuma K, Tominaga T

    10th Korea-Japan Joint Stroke Conference　2022/09/17

  25. 脳梗塞に対する新規治療法開発への挑戦 Invited

    新妻 邦泰

    第27回新潟神経疾患研究会　2022/09/08

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    新潟県医師会生涯教育講座／大学院特別講義

  26. SAH ICU管理の標準化に向けて －クラゾセンタンの有効性と安全性－ Invited

    新妻邦泰

    第63回（一社）日本脳神経外科学会東北支部会　2022/09/03

  27. Development of a Futuristic Supporting System for Neuroendovascular Therapy International-presentation Invited

    Kuniyasu Niizuma

    The 18th Interdisciplinary Cerebrovascular Symposium (ICS2022)　2022/08/27

  28. トランスレイショナルリサーチ：基礎から臨床へ橋渡しする方法と実際 失敗と工夫 Invited

    新妻邦泰

    第22回日本分子脳神経外科学会　2022/07/23

  29. Application of Muse Cell Therapy to Stroke International-presentation Invited

    Niizuma K, Tominaga T

    The 30th International Symposium on Cerebral Blood Flow, Metabolism and Function (BRAIN & BRAIN PET 2022)　2022/06/01

  30. くも膜下出血後脳血管攣縮治療の現在とICU 管理の今後 Invited

    新妻邦泰

    第42回日本脳神経外科コングレス総会　2022/05/14

  31. 新規脳梗塞治療薬SMTPの開発と臨床への橋渡し Invited

    新妻 邦泰, 冨永 悌二

    第37回NPO法人日本脳神経血管内治療学会学術集会　2021/11/27

  32. 脳梗塞患者を対象とした他家Muse細胞製品CL2020の治療成績：ランダム化プラセボ対照二重盲検試験 Invited

    新妻邦泰, 大沢伸一郎, 遠藤英徳, 出江紳一, 安宅航太, 平川晃弘, 岩野政雄, 冨永悌二

    第80回日本脳神経外科学会学術総会　2021/10/27

  33. 新規脳梗塞治療薬SMTPの開発 Invited

    新妻邦泰, 冨永悌二

    第80回日本脳神経外科学会学術総会　2021/10/27

  34. Development of a digital supporting system for neuroendovascular therapy International-presentation Invited

    Kuniyasu Niizuma, Masaaki Shojima, Makoto Ohta, Yoshihiro Okamoto, Takashi Kosugi, Teiji Tominaga

    The 15th Japan - Korea Joint Conference on Surgery for Cerebral Stroke (JKJC 2021)　2021/09/10

  35. NIRSの臨床的有用性 ～脳神経外科の観点から考える～ Invited

    新妻邦泰

    第68回日本麻酔科学会年次学術集会　2021/06/03

  36. 脳梗塞に対する新規治療の開発 Invited

    新妻邦泰, 冨永悌二

    第41回日本脳神経外科コングレス総会　2021/05/16

  37. 新規脳梗塞治療薬の開発と臨床への橋渡し

    新妻邦泰

    第50回脳卒中の外科学会学術集会　2021/03/13

  38. Muse細胞を用いた新規脳梗塞治療の開発 Invited

    新妻邦泰

    第46回日本脳卒中学会学術集会　2021/03/11

  39. Optimal Model to Advanced Cell-based Therapy International-presentation Invited

    Asia Pacific Stroke Conference 2020　2020/12/06

  40. 中枢神経疾患に対する新規細胞治療の開発 Invited

    新妻邦泰

    第63回日本脳循環代謝学会学術集会　2020/11/13

  41. 水流での剥離操作を用いて内視鏡下に摘出した橋前槽～第三脳室類上皮腫の2手術例

    新妻邦泰, 石田朋久, 大沢伸一郎, 遠藤英徳, 冨永悌二

    第27回日本神経内視鏡学会　2020/11/06

  42. 脳梗塞に対する幹細胞治療の基礎から臨床への橋渡し Invited

    新妻邦泰

    日本脳神経外科学会第79回学術総会　2020/10/15

  43. 健康長寿を達成するための明日への取り組み－脳卒中を克服するための新規治療開発－ Invited

    新妻邦泰, 冨永悌二

    第18回日本臨床医療福祉学会　2020/10/10

  44. Muse細胞による神経再生医療の開発 Invited

    新妻邦泰

    第44回日本神経心理学会学術集会　2020/10/01

  45. Muse cell treatment for cerebral ischemia Invited

    新妻邦泰

    第61回日本神経学会学術大会　2020/09/01

  46. 新規脳梗塞治療薬SMTPの開発 Invited

    新妻邦泰, 伊藤明, 清水宏明, 冨永悌二

    第45回日本脳卒中学会学術集会　2020/08/25

  47. 脳虚血に対する橋渡し研究 Invited

    新妻邦泰, 冨永悌二

    第40回日本脳神経外科コングレス総会　2020/08/12

  48. 脳動脈瘤に対する治療医シミュレーション・再発予測 Invited

    新妻邦泰, 杉山慎一郎, 佐藤健一, 松本康史, 伊藤明, 冨永悌二

    第43回日本脳神経CI学会総会　2020/01/24

  49. 脳梗塞治療の INNOVATION～東北大学における取り組み～ Invited

    新妻邦泰

    第62回日本脳循環代謝学会学術集会　2019/11/29

  50. 血管内治療支援装置の開発 Invited

    新妻邦泰

    第62回日本脳循環代謝学会学術集会　2019/11/29

  51. Choroidal arteryを標的とした側脳室三角部髄膜腫の塞栓術

    新妻邦泰, 遠藤英徳, 針生新也, 西嶌泰生, 冨永悌二

    第35回日本脳神経血管内治療学会学術総会　2019/11/23

  52. 脳梗塞に対する新規治療法の開発 Invited

    新妻邦泰

    第59回日本臨床化学会年次学術集会　2019/09/29

  53. 脳梗塞に対する Muse 細胞治療の開発 Invited

    新妻邦泰, 冨永悌二

    創薬薬理フォーラム第27回シンポジウム　2019/09/12

  54. Muse細胞による再生医療について Invited

    新妻邦泰, 冨永悌二

    第1回日本スティミュレーションセラピー学会学術大会　2019/08/03

  55. A novel model of cerebral hyperperfusion with blood brain barrier breakdown, white matter injury, and cognitive dysfunction International-presentation

    K. Niizuma, A. Mansour, S. Rashad, M. Fujimura, T. Tominaga

    The 29th International Symposium on Cerebral Blood Flow, Metabolism and Function (BRAIN & BRAIN PET 2019)　2019/07/07

  56. Muse 細胞を用いた再生医療 ～脳梗塞新規治療の開発～ Invited

    新妻邦泰

    第10回ニューロリハビリテーション学会学術集会　2019/04/29

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    アカデミックレクチャー

  57. Muse Cell Transplantation to Treat Cerebral Ischemia International-presentation Invited

    Kuniyasu Niizuma, Teiji Tominaga

    2019/04/27

  58. 脳梗塞に対するMuse細胞治療の開発 Invited

    新妻邦泰, 冨永悌二

    第28回脳神経外科手術と機器学会（CNTT2019）　2019/04/13

  59. Muse細胞を用いた脳梗塞医再生治療 Invited

    新妻 邦泰

    第44回日本脳卒中学会学術集会　2019/03/22

  60. Muse細胞による脳梗塞治療 Invited

    新妻 邦泰

    第18回日本再生医療学会総会　2019/03/21

  61. アプリで参加！君の診断は？ Invited

    新妻 邦泰

    第34回NPO法人日本脳神経血管内治療学会学術総会　2018/11/22

  62. 脳梗塞における新規治療法開発：新規血栓溶解薬およびMuse細胞治療 Invited

    新妻 邦泰

    日本脳神経外科学会第77回総会　2018/10/11

  63. Muse細胞による脳梗塞治療 Invited

    新妻 邦泰

    日本脳神経外科学会第77回総会　2018/10/10

  64. Muse細胞による脳梗塞治療 Invited

    新妻 邦泰

    第43回脳卒中学会学術集会　2018/03/17

Show all Show first 5

Industrial Property Rights 5

  1. 血流場推定装置、学習装置、血流場推定方法及びプログラム

    安西 眸, 渡邉 和浩, ガオヤン リー, 太田 信, 冨永 悌二, 新妻 邦泰, 杉山 慎一郎

    特許第7462925号

    Property Type: Patent

  2. カテーテル操作支援装置及びその作動方法、プログラム、並びにX線医療システム

    小杉 隆司, 太田 信, 冨永 悌二, 新妻 邦泰, 庄島 正明, 岡本 吉弘, 坂井 信幸

    特許第7179288号

    Property Type: Patent

  3. 毛髪損傷の治療剤

    新妻 邦泰, 冨永 悌二

    Property Type: Patent

  4. 脳出血を治療又は予防するための薬剤及び該薬剤を用いて脳出血を治療又は予防する方法

    冨永 悌二, 新妻 邦泰

    Property Type: Patent

  5. 生体固定用複合材料

    西澤 松彦, 長峯 邦明, 冨永 悌二, 齋木 佳克, 荒井 陽一, 新倉 仁, 井樋 栄二, 香取 幸夫, 岩▲崎▼ 真樹, 中川 敦寛, 川口 奉洋, 新妻 邦泰, 徳江 彩子, 遠藤 俊毅, 萩原 嘉廣, 綿貫 宗則, 橋本 功

    Property Type: Patent

Research Projects 40

  1. 次世代光技術を用いた革新的脳腫瘍制御法の創発 Competitive

    新妻 邦泰

    Offer Organization: 国立研究開発法人科学技術振興機構

    System: 創発的研究支援事業

    2023/04 - 2030/03

  2. 脳カテーテル用生体磁気センサシステムの開発と神経磁界の検出

    薮上 信, 新妻 邦泰

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2024/06/28 - 2027/03/31

  3. 血管壁MRイメージングと数値流体解析を駆使した脳動脈瘤増大予測モデルの開発

    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

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04/01 - 2027/03/31

  4. A novel therapeutic approach for cerebral infarction via blood brain barrier protection by S1PR1 agonist

    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

    2024/04/01 - 2027/03/31

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

    More details Close

    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。

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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。

  19. 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

  20. 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。、

  21. 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。

  22. 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。

  23. 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

  24. 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.

  25. 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。

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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）.

  32. 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.

  33. 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.

  34. 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.

  35. 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。

  36. 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.

  37. 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.

  38. 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.

  39. 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.

  40. 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 9

  1. ishinomaki

    2019/09/23 - 2019/09/23

  2. 脳神経領域の新規治療開発

    令和5年度宮城県仙台第二高等学校「一日大学」　仙台市

    2023/12/14 - 2023/12/14

  3. 脳神経領域の新規治療開発

    令和4年度 宮城県仙台二高等学校 [一日大学]　仙台市

    2022/12/08 - 2022/12/08

  4. 脳卒中について

    県民の健康と医療を考えるセミナー　オンライン

    2022/11/27 - 2022/11/27

  5. 「中枢神経疾患新規治療法開発への挑戦！」～Muse細胞による神経機能再建～

    宮城県ゆずり葉の会講演会　オンライン

    2021/12/04 - 2021/12/04

  6. 再生医療

    全国遷延性意識障害者・家族の会 第三回 学会・家族会合同ミーティング　オンライン

    2021/01/29 - 2021/01/29

  7. 脳神経領域の新規治療開発

    令和元年度 宮城県仙台第二高等学校 ［一日大学］　仙台市

    2019/12/12 - 2019/12/12

  8. 最新！脳の再生治療

    日本脳神経外科学会第77回総会 市民公開講座　仙台市

    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」）

  9. 脳卒中と脳出血の話題「脳卒中の話」

    第23回市民医学講座　仙台市

    2017/05/24 - 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」）

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