東北大学研究者紹介

研究者詳細

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顔写真

ニイヅマ　クニヤス

新妻　邦泰

Kuniyasu Niizuma

所属

大学院医工学研究科　生体再生医工学講座（神経再建医工学分野）

職名

教授

学位

博士（医学）（東北大学）

researchmap

https://researchmap.jp/7000014649

J-GLOBAL ID

201601013654351269

所属学協会 12

日本神経内視鏡学会
日本脳神経CI学会
日本脊髄外科学会
日本磁気共鳴医学会
日本脳神経外科コングレス
日本分子脳神経外科学会
日本脳循環代謝学会
日本脳卒中学会
日本脳卒中の外科学会
日本再生医療学会
日本脳神経血管内治療学会
日本脳神経外科学会

︎全件表示 ︎最初の5件までを表示

研究キーワード 5

脳梗塞
再生医療
脳神経外科
脳卒中
脳血管内治療

研究分野 1

ライフサイエンス / 脳神経外科学 /

受賞 1

第15回日本脳神経外科学会奨励賞

2009年10月15日　日本脳神経外科学会

論文 238

Retrospective interviews reveal unawareness of weakness following reversible hemispheric suppression: An exploratory study using selective anesthesia for functional evaluation. 国際誌

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年7月5日

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.
Decreased Lactococcus lactis and propionic acid in feces of patients with Moyamoya disease: Possible implications of immune dysregulation. 国際誌

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年3月26日

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.
Multilineage-differentiating stress-enduring cells attenuate the cognitive impairment caused by chronic cerebral hypoperfusion in rats. 国際誌

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

Experimental neurology　387　115185-115185　2025年2月12日

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.
Transcriptome-wide alternative mRNA splicing analysis reveals post-transcriptional regulation of neuronal differentiation. 国際誌

Yuan Zhou, Sherif Rashad, Kuniyasu Niizuma

The FEBS journal　292　(8)　2051-2070　2025年1月24日

DOI： 10.1111/febs.17408 　

ISSN：1742-464X

eISSN：1742-4658
Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation. 国際誌

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

International journal of molecular sciences　26　(2)　2025年1月15日

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.
Publisher Correction: High-throughput fluorescence lifetime imaging flow cytometry. 国際誌

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年1月10日

DOI： 10.1038/s41467-025-55961-4 　
Mechanical thrombectomy for cerebral embolism due to cardiac papillary fibroelastoma: A case report. 国際誌

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

Surgical neurology international　16　141-141　2025年

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.
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年

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.
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年
出版者・発行元： 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.
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年12月2日

DOI： 10.35848/1347-4065/ad9a6f 　

ISSN：0021-4922

eISSN：1347-4065
Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A. 国際誌

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

Journal of cellular physiology　240　(1)　e31477　2024年11月8日

DOI： 10.1002/jcp.31477 　

ISSN：0021-9541

eISSN：1097-4652
Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke. 国際誌

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年11月7日

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.
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年11月
出版者・発行元： (一社)日本脳神経血管内治療学会
eISSN：2759-6907
High-throughput optical imaging technology for large-scale single-cell analysis of live Euglena gracilis 査読有り

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年11月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.trac.2024.117938 　

ISSN：0165-9936
Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen. 国際誌

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年10月13日

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

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

Journal of neurosurgery. Case lessons　8　(11)　2024年9月9日

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.
High-throughput fluorescence lifetime imaging flow cytometry. 国際誌

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年9月4日

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.
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年9月
出版者・発行元： (一社)日本てんかん学会
ISSN：0912-0890

eISSN：1347-5509
Aneurysm Wall Enhancement Can Predict Rupture Point in Intracranial Aneurysms With Multiple Blebs. 国際誌

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

Neurosurgery　96　(3)　593-599　2024年8月8日

DOI： 10.1227/neu.0000000000003134 　

ISSN：0148-396X

eISSN：1524-4040
Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit. 国際誌

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年5月19日

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.
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年5月
出版者・発行元： (一社)日本脳卒中の外科学会
ISSN：0914-5508

eISSN：1880-4683
Author Correction: Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation. 国際誌

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年4月2日

DOI： 10.1038/s41551-024-01200-y 　
Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment. 国際誌

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

Stem cells translational medicine　13　(6)　532-545　2024年4月1日

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

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

Journal of neurosurgery. Case lessons　7　(9)　2024年2月26日

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

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

BMC cancer　24　(1)　222-222　2024年2月16日

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.
Translational response to mitochondrial stresses is orchestrated by tRNA modifications. 国際誌

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年2月14日

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.
Assessment of language lateralization in epilepsy patients using the super-selective Wada test. 国際誌

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年2月10日

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.
The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease. 国際誌

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年2月1日

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.
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年

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.
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年1月
出版者・発行元： (株)医学書院
ISSN：0301-2603

eISSN：1882-1251
Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study. 国際誌

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年

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.
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年

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.
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. 国際誌

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年12月25日

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

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年11月20日

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.
Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation. 国際誌

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年11月9日

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.
Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury. 国際誌

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

International journal of molecular sciences　24　(19)　2023年9月27日

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.
Randomized placebo-controlled trial of CL2020, an allogenic muse cell-based product, in subacute ischemic stroke. 国際誌

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年9月27日

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).
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年9月23日

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.
【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年3月
出版者・発行元： (株)メディカ出版
ISSN：0917-1495
Olfactory Dysfunction, an Often Neglected Symptom of Hydrocephalus: Experience from a Case of Late-Onset Idiopathic Aqueductal Stenosis 国際誌

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年3月1日
出版者・発行元： 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.
A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol. 国際誌

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年12月23日

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.
Retiform endothelial hyperplasia mimicking cavernous malformation as a late complication of Gamma Knife radiosurgery. 国際誌

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

Journal of neurosurgery　139　(1)　1-11　2022年12月23日

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.
Determination of language areas in patients with epilepsy using the super-selective Wada test. 国際誌

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年12月

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

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年11月3日

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

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年10月17日

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.
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年9月

DOI： 10.1016/j.inat.2022.101560 　

eISSN：2214-7519
Correction to: Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. 国際誌

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年8月15日

DOI： 10.1186/s13104-022-06167-0 　
Codon usage and mRNA stability are translational determinants of cellular response to canonical ferroptosis inducers 国際誌

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年8月
出版者・発行元： 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.
Plasma tRNA derivatives concentrations for detecting early brain damage in patients with acute large vessel occlusion and predicting clinical outcomes after endovascular thrombectomy. 国際誌

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年7月1日

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.
RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses. 国際誌

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年6月25日

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

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

Journal of neurosurgery　137　(6)　1-11　2022年4月1日

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).
Morphological comparison of masseter muscle fibers in the mandibular rest and open positions using diffusion tensor imaging. 国際誌

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年3月25日

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.
Methodological assessment of the reduction of dissemination risk and quantification of debris dispersion during dissection with a surgical aspirator. 国際誌

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年3月2日

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.
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年2月

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.
Wall enhancement in unruptured posterior communicating aneurysms with oculomotor nerve palsy on magnetic resonance vessel wall imaging. 国際誌

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

Journal of neurosurgery　1-7　2022年1月21日

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.
Quantitative assessment of microstructural evolution of intracranial aneurysm wall by vessel wall imaging. 国際誌

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

Neuroradiology　64　(7)　1343-1350　2022年1月8日

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

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年

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

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

Surgical neurology international　13　85-85　2022年

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

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

Radiology case reports　16　(12)　3721-3728　2021年12月

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.
Intraoperative motor-evoked potential monitoring during coil embolization for anterior choroidal artery aneurysms. 国際誌

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

Neuroradiology　64　(6)　1221-1229　2021年11月17日

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.
Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease. 国際誌

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年10月28日

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.
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. 国際誌

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

Journal of neurosurgery. Case lessons　2　(12)　CASE21447　2021年9月20日

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

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

Neuroradiology　64　(3)　575-585　2021年9月9日

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.
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年8月26日

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.
Digital intravascular pressure wave recording during endovascular treatment reveals abnormal shunting flow in vertebral venous fistula of the vertebral artery: illustrative case. 国際誌

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

Journal of neurosurgery. Case lessons　2　(2)　CASE21172　2021年7月12日

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.
Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation. 国際誌

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年5月10日

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.
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年5月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN：2423-9119

eISSN：2424-1709
The cell and stress-specific canonical and noncanonical tRNA cleavage. 国際誌

Sherif Rashad, Teiji Tominaga, Kuniyasu Niizuma

Journal of cellular physiology　236　(5)　3710-3724　2021年5月

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.
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. 国際誌

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年2月17日

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.
Brain Temperature Measured by Magnetic Resonance Spectroscopy to Predict Clinical Outcome in Patients with Infarction. 国際誌

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

Sensors (Basel, Switzerland)　21　(2)　2021年1月12日

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.
Comparison between ultra-high-resolution computed tomographic angiography and conventional computed tomographic angiography in the visualization of the subcallosal artery. 国際誌

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年

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.
Basilar artery dissection with rupture 6 years after accidental detection: A case report. 国際誌

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

Surgical neurology international　12　4-4　2021年

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.
Association of intravenous administration of human Muse cells with deficit amelioration in a rat model of spinal cord injury. 国際誌

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年1月1日

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.
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. 国際誌

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

Journal of neurosurgery　1-8　2020年10月23日

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.
Physiologic blood flow is turbulent. 国際誌査読有り

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

Scientific reports　10　(1)　15492-15492　2020年9月23日

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.
Cell-Based Therapy for Stroke: Musing With Muse Cells. 国際誌査読有り

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

Stroke　51　(9)　2854-2862　2020年9月

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.
Intractable Hiccups as the Primary Symptom of a Perimedullary Arteriovenous Fistula at the Craniocervical Junction. 国際誌査読有り

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

World neurosurgery　141　64-68　2020年9月

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.
Direct Inspection with Dual Endoscope Technique via Bilateral Transforaminal Approach Leading to Complete Resection of Recurrent Colloid Cyst of the Third Ventricle. 国際誌査読有り

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

World neurosurgery　141　272-277　2020年9月

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.
The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation. 国際誌査読有り

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

RNA biology　17　(8)　1092-1103　2020年8月

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.
Preliminary Study of Eye-Tracking During the Coil Insertion Task in a Silastic Model of Intracranial Aneurysms. 国際誌査読有り

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

World neurosurgery　139　e827-e835　2020年7月

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.
Stress Induced tRNA Halves (tiRNAs) as Biomarkers for Stroke and Stroke Therapy; Pre-clinical Study. 国際誌査読有り

Kanako Sato, Sherif Rashad, Kuniyasu Niizuma, Teiji Tominaga

Neuroscience　434　44-54　2020年5月10日

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.
Symptomatic Cerebral Hyperperfusion After Cerebral Vasospasm Associated with Aneurysmal Subarachnoid Hemorrhage. 国際誌査読有り

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

World neurosurgery　137　379-383　2020年5月

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.
Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach. 国際誌査読有り

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年4月16日

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.
Author Correction: The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. 国際誌査読有り

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

Scientific reports　10　(1)　6217-6217　2020年4月7日

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.
Ruptured Basilar Artery Dissection Diagnosed Using Magnetic Resonance Vessel Wall Imaging and Treated with Coil Embolization with Overlapping LVIS Stents: A Case Report. 査読有り

Shinya Sonobe, Masahiro Yoshida, Kuniyasu Niizuma, Teiji Tominaga

NMC case report journal　7　(2)　75-79　2020年4月

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.
Optimal Timing of Extracranial-Intracranial Bypass with Microsurgical Trapping for Ruptured Blister Aneurysms of the Internal Carotid Artery. 国際誌査読有り

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

World neurosurgery　136　e567-e577　2020年4月

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.
Case reports of latent HBV hepatitis in patients after neurosurgical treatment for hypothalamic and pituitary tumors. 国際誌査読有り

Kuniyasu Niizuma, Yoshikazu Ogawa, Takayuki Kogure, Teiji Tominaga

BMC infectious diseases　20　(1)　230-230　2020年3月18日

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.
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年3月
出版者・発行元： (一社)日本脊椎脊髄病学会
ISSN：1884-7137

eISSN：2435-1563
The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study. 国際誌査読有り

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

Scientific reports　10　(1)　3700-3700　2020年2月28日

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.
Octacalcium phosphate collagen composite (OCP/Col) enhance bone regeneration in a rat model of skull defect with dural defect. 国際誌査読有り

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年2月

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.
Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model. 国際誌査読有り

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年2月

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.
Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano-miRNAs. 国際誌査読有り

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

Journal of cellular physiology　235　(11)　7827-7839　2020年1月8日

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.
XGBoost, a Machine Learning Method, Predicts Neurological Recovery in Patients with Cervical Spinal Cord Injury 査読有り

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年1月1日
出版者・発行元： Mary Ann Liebert Inc
DOI： 10.1089/neur.2020.0009 　

eISSN：2689-288X
Preliminary study of eye tracking to investigate the differences in gaze behaviors depending on the experience of neuroendovascular therapy. 国際誌

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年

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.
Prediction of Functional Outcome in Patients with Acute Stroke by Measuring tRNA Derivatives. 国際誌

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年

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.
A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood 査読有り

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年1月1日
出版者・発行元： 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.
Efficacy of intra-arterial indocyanine green angiography for the microsurgical treatment of dural arteriovenous fistula: A case report. 国際誌査読有り

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

Surgical neurology international　11　46-46　2020年

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.
tRNA cleavage: a new insight. 国際誌査読有り

Rashad S, Niizuma K, Tominaga T

Neural regeneration research　15　(1)　47-52　2020年1月

DOI： 10.4103/1673-5374.264447 　

ISSN：1673-5374
A novel model of cerebral hyperperfusion with blood-brain barrier breakdown, white matter injury, and cognitive dysfunction. 国際誌査読有り

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

Journal of neurosurgery　1-13　2019年10月18日

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.
Circumferential wall enhancement in evolving intracranial aneurysms on magnetic resonance vessel wall imaging. 査読有り

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年10月

DOI： 10.3171/2018.5.JNS18322 　

ISSN：0022-3085
Arterial blood pressure correlates with 90-day mortality in sepsis patients: a retrospective multicenter derivation and validation study using high-frequency continuous data. 国際誌査読有り

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年10月

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.
Genetic analysis of ring finger protein 213 (RNF213) c.14576G>A polymorphism in patients with vertebral artery dissection: a comparative study with moyamoya disease. 国際誌査読有り

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

Neurological research　41　(9)　811-816　2019年9月

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.
Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases. 国際誌査読有り

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年9月

DOI： 10.1080/02688697.2019.1667482 　

ISSN：0268-8697
tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells. 国際誌査読有り

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

Brain research　1714　8-17　2019年7月1日

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.
What does computational fluid dynamics tell us about intracranial aneurysms? A meta-analysis and critical review. 国際誌査読有り

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年6月18日

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.
Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia. 査読有り

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年4月

DOI： 10.1016/j.jocn.2019.04.012 　

ISSN：0967-5868
Transsphenoidal Removal of Retroclival Chondroma with Pituitary Transposition Manifesting as Repeated Subarachnoid Hemorrhage: A Case Report. 査読有り

Ogawa Y, Niizuma K, Tominaga T

Journal of neurological surgery. Part A, Central European neurosurgery　80　(3)　228-232　2019年2月

DOI： 10.1055/s-0038-1677452 　

ISSN：2193-6315
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. 国際誌査読有り

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年

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.
Incidence and Risk Factors of the Watershed Shift Phenomenon after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis for Adult Moyamoya Disease. 国際誌査読有り

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年

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.
Mechanical Thrombectomy for Acute Ischemic Stroke Arising from Thrombus of the Left Superior Pulmonary Vein Stump after Left Pneumonectomy: A Case Report. 査読有り

Sonobe S, Yoshida M, Niizuma K, Tominaga T

NMC case report journal　6　(1)　17-20　2019年1月

DOI： 10.2176/nmccrj.cr.2018-0163 　
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. 国際誌査読有り

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年

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.
Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels as a Biomarker of Acute Intracerebral Hemorrhage. 査読有り

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年11月
出版者・発行元：
DOI： 10.1016/j.jstrokecerebrovasdis.2018.10.027 　

ISSN：1052-3057
Cord Compression Caused by a Tangled and Warped Lumbar Catheter After Lumboperitoneal Shunt Placement. 査読有り

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

Neurospine　2018年10月

DOI： 10.14245/ns.1836114.057 　

ISSN：2586-6583
Quantitative Characterization of Carotid Plaque Components Using MR Apparent Diffusion Coefficients and Longitudinal Relaxation Rates at 3T: A Comparison With Histology. 国際誌査読有り

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年10月

DOI： 10.1002/jmri.26216 　

ISSN：1053-1807
A refined model of chronic cerebral hypoperfusion resulting in cognitive impairment and a low mortality rate in rats. 国際誌査読有り

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年9月7日

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.
Stress-induced tRNA cleavage and tiRNA generation in rat neuronal PC12 cells. 国際誌査読有り

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

Journal of neurochemistry　146　(5)　560-569　2018年9月

DOI： 10.1111/jnc.14321 　

ISSN：0022-3042

詳細を見る詳細を閉じる

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.
Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge. 国際誌査読有り

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年9月

DOI： 10.1007/s13239-018-00374-2 　

ISSN：1869-408X
Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation. 国際誌査読有り

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年9月

DOI： 10.1007/s13239-018-00376-0 　

ISSN：1869-408X
Metabolomic Analysis of Mouse Brain after a Transient Middle Cerebral Artery Occlusion by Mass Spectrometry Imaging. 査読有り

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年9月

DOI： 10.2176/nmc.oa.2018-0054 　

ISSN：0470-8105
[Surgical Planning for a Giant Pituitary Adenoma Based on Evaluation of the Fine Feeding System and Angioarchitecture:A Case Report]. 査読有り

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

No shinkei geka. Neurological surgery　46　(8)　691-697　2018年8月

DOI： 10.11477/mf.1436203795 　

ISSN：0301-2603
Biphasic Development of Focal Cerebral Hyperperfusion After Revascularization Surgery for Adult Moyamoya Disease Associated With Autosomal Dominant Polycystic Kidney Disease. 国際誌査読有り

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年8月

DOI： 10.1016/j.jstrokecerebrovasdis.2018.07.024 　

ISSN：1052-3057
Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia 査読有り

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年8月1日
出版者・発行元： Elsevier Ltd
DOI： 10.1016/j.neuroscience.2018.05.015 　

ISSN：1873-7544 0306-4522
Paradoxical Association of Symptomatic Local Vasogenic Edema with Global Cerebral Hypoperfusion after Direct Revascularization Surgery for Adult Moyamoya Disease. 国際誌査読有り

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年8月

DOI： 10.1016/j.jstrokecerebrovasdis.2018.03.002 　

ISSN：1052-3057
Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis. 査読有り

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

Brain research　1699　54-68　2018年7月

DOI： 10.1016/j.brainres.2018.06.029 　

ISSN：0006-8993
Mid-term prognosis of non-functioning pituitary adenomas with high proliferative potential: really an aggressive variant? 査読有り

Yoshikazu Ogawa, Hidefumi Jokura, Kuniyasu Niizuma, Teiji Tominaga

Journal of Neuro-Oncology　137　(3)　543-549　2018年5月1日
出版者・発行元： Springer New York LLC
DOI： 10.1007/s11060-017-2740-1 　

ISSN：1573-7373 0167-594X
Accelerating Cell Therapy for Stroke in Japan: Regulatory Framework and Guidelines on Development of Cell-Based Products. 国際誌査読有り

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年4月

DOI： 10.1161/STROKEAHA.117.019216 　

ISSN：0039-2499
Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms 査読有り

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年3月1日
出版者・発行元： American Association of Neurological Surgeons
DOI： 10.3171/2016.10.JNS161695 　

ISSN：1933-0693 0022-3085
Clinical Characteristics of Lumbosacral Spinal Dural Arteriovenous Fistula (DAVF)–Comparison with Thoracic DAVF 査読有り

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

World Neurosurgery　110　e383-e388　2018年2月1日
出版者・発行元： Elsevier Inc.
DOI： 10.1016/j.wneu.2017.11.002 　

ISSN：1878-8769 1878-8750
Increased serum production of soluble CD163 and CXCL5 in patients with moyamoya disease: Involvement of intrinsic immune reaction in its pathogenesis. 国際誌査読有り

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

Brain research　1679　39-44　2018年1月15日

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.
Efficacy and safety of REVIVE SE thrombectomy device for acute ischemic stroke: River Japan (reperfuse ischemic vessels with endovascular recanalization device in Japan) 査読有り

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年
出版者・発行元： Japan Neurosurgical Society
DOI： 10.2176/nmc.oa.2017-0145 　

ISSN：1349-8029 0470-8105
Embolization of ruptured arteriovenous malformations in the cerebellopontine angle cistern 査読有り

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

Neurosurgical Review　41　(1)　173-182　2018年1月1日
出版者・発行元： Springer Verlag
DOI： 10.1007/s10143-017-0832-1 　

ISSN：1437-2320 0344-5607
Application of Muse Cell Therapy to Stroke. 査読有り

Niizuma K, Borlongan CV, Tominaga T

Advances in experimental medicine and biology　1103　167-186　2018年

DOI： 10.1007/978-4-431-56847-6_9 　

ISSN：0065-2598
Patient with Recurrent Anterior Cerebral Artery Dissecting Aneurysm After Stent-Assisted Coil Embolization Successfully Treated with A3-A3 Anastomosis 査読有り

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

World Neurosurgery　109　77-81　2018年1月1日
出版者・発行元： Elsevier Inc.
DOI： 10.1016/j.wneu.2017.09.128 　

ISSN：1878-8769 1878-8750
Recovery from diabetes insipidus and preservation of thyroid function after craniopharyngioma removal and pituitary stalk sectioning 査読有り

Yoshikazu Ogawa, Kuniyasu Niizuma, Teiji Tominaga

CLINICAL NEUROLOGY AND NEUROSURGERY　162　36-40　2017年11月

DOI： 10.1016/j.clineuro.2017.09.005 　

ISSN：0303-8467

eISSN：1872-6968
Intra-operative hemorrhage due to hyperperfusion during direct revascularization surgery in an adult patient with moyamoya disease: a case report 査読有り

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

NEUROSURGICAL REVIEW　40　(4)　679-684　2017年10月

DOI： 10.1007/s10143-017-0868-2 　

ISSN：0344-5607

eISSN：1437-2320
Transient Global Cerebral Ischemia Induces RNF213, a Moyamoya Disease Susceptibility Gene, in Vulnerable Neurons of the Rat Hippocampus CA1 Subregion and Ischemic Cortex 査読有り

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年9月

DOI： 10.1016/j.jstrokecerebrovasdis.2017.06.032 　

ISSN：1052-3057

eISSN：1532-8511
食道癌放射線治療後に生じたcarotid blowout syndromeに対する血管内治療：症例報告査読有り

高橋重文, 川口奉洋, 新妻邦泰, 中川敦寛, 藤村幹, 小川武則, 香取幸夫, 冨永悌二

Neurological Surgery 脳神経外科　45　(9)　791-798　2017年9月1日
出版者・発行元：
DOI： 10.11477/mf.1436203594 　

ISSN：1882-1251 0301-2603

eISSN：1882-1251
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 査読有り

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

NEUROSURGICAL REVIEW　40　(3)　517-521　2017年7月

DOI： 10.1007/s10143-017-0866-4 　

ISSN：0344-5607

eISSN：1437-2320
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' 査読有り

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

NEUROSURGICAL REVIEW　40　(3)　507-512　2017年7月

DOI： 10.1007/s10143-017-0845-9 　

ISSN：0344-5607

eISSN：1437-2320
Circumferential Wall Enhancement on Magnetic Resonance Imaging is Useful to Identify Rupture Site in Patients with Multiple Cerebral Aneurysms 査読有り

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

Neurosurgery　2017年6月6日

DOI： 10.1093/neuros/nyx267 　
Fine morphological evaluation of hypothalamus in patients with hyperphagia 査読有り

Yoshikazu Ogawa, Kuniyasu Niizuma, Teiji Tominaga

ACTA NEUROCHIRURGICA　159　(5)　865-871　2017年5月

DOI： 10.1007/s00701-017-3112-5 　

ISSN：0001-6268

eISSN：0942-0940
Embolization of the choroidal artery in the treatment of cerebral arteriovenous malformations 査読有り

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年4月

DOI： 10.3171/2016.2.JNS152370 　

ISSN：0022-3085

eISSN：1933-0693
Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model 査読有り

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

STROKE　48　(2)　428-435　2017年2月

DOI： 10.1161/STROKEAHA.116.014950 　

ISSN：0039-2499

eISSN：1524-4628
出血発症もやもや病の治療戦略査読有り

藤村幹, 遠藤英徳, 新妻邦泰, 冨永悌二

脳神経外科ジャーナル　26　(2)　112-116　2017年2月
出版者・発行元：日本脳神経外科コングレス
DOI： 10.7887/jcns.26.112 　

詳細を見る詳細を閉じる

<p> 頭蓋外内血行再建術は脳虚血症状を有するもやもや病に対する有効な治療法である. Japan Adult Moyamoya trialの結果を受け, 直接血行再建術を含めた血行再建術の適応は成人出血発症例にも近年拡大傾向にある. 中でも後方循環系の出血例に対しては血行再建術による再出血予防効果が高く, 手術が特に勧められる. JAM trial後の当該施設における成人出血発症例に対する直接間接複合手術の結果も良好であり, 成人出血発症例に対する血行再建術は有効な安全, 有効な治療法と考えられた. 周術期においては脳虚血, 過灌流症候群の回避が重要である.</p>
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

生体医工学　55　(5)　412-412　2017年
出版者・発行元：公益社団法人日本生体医工学会
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>
テキストマイニングによる敗血症患者の看護カルテ自由記載中の語句と転帰に関する検討．査読有り

小林直也, 中川敦寛, 石垣司, 工藤大介, 新妻邦泰, 川口奉洋, 冨永悌二, 山内正憲

日本集中治療医学会雑誌　24　(6)　631-632　2017年
出版者・発行元：一般社団法人日本集中治療医学会
DOI： 10.3918/jsicm.24_631 　
Prediction of the initiation of cerebral aneurysms -Progress over view FY2016- 査読有り

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

Proc 3rd Int Symp Multidiscipl Comput Anat　A03-KB001　2017年
De Novo Development of Moyamoya Disease in an Adult Female with a Genetic Variant of the RNF-213 Gene: Case Report 査読有り

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年1月

DOI： 10.1016/j.jstrokecerebrovasdis.2016.09.035 　

ISSN：1052-3057

eISSN：1532-8511
Daughter Sac Formation Related to Blood Inflow Jet in an Intracranial Aneurysm 査読有り

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年12月

DOI： 10.1016/j.wneu.2016.09.040 　

ISSN：1878-8750

eISSN：1878-8769
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年11月
出版者・発行元： (一社)日本脳循環代謝学会
ISSN：0915-9401

eISSN：2188-7519
Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization 査読有り

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年10月

DOI： 10.1161/STROKEAHA.116.013555 　

ISSN：0039-2499

eISSN：1524-4628
Development of Abnormal Hemispheric Vascular Networks Mimicking Cerebral Proliferative Angiopathy in a Child Originally Diagnosed with Deep-Seated Arteriovenous Fistula 査読有り

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

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

DOI： 10.1016/j.jstrokecerebrovasdis.2016.07.042 　

ISSN：1052-3057

eISSN：1532-8511
Long-term follow-up of pediatric moyamoya disease treated by combined direct-indirect revascularization surgery: single institute experience with surgical and perioperative management 査読有り

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

NEUROSURGICAL REVIEW　39　(4)　615-622　2016年10月

DOI： 10.1007/s10143-016-0734-7 　

ISSN：0344-5607

eISSN：1437-2320
Ischemic pituitary adenoma apoplexy-Clinical appearance and prognosis after surgical intervention 査読有り

Yoshikazu Ogawa, Kuniyasu Niizuma, Shunji Mugikura, Teiji Tominaga

CLINICAL NEUROLOGY AND NEUROSURGERY　148　142-146　2016年9月

DOI： 10.1016/j.clineuro.2016.07.013 　

ISSN：0303-8467

eISSN：1872-6968
Quantitative Assessment of Circumferential Enhancement along the Wall of Cerebral Aneurysms Using MR Imaging 査読有り

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年7月

DOI： 10.3174/ajnr.A4722 　

ISSN：0195-6108

eISSN：1936-959X
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 査読有り

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年7月

DOI： 10.1016/j.brainres.2016.03.009 　

ISSN：0006-8993

eISSN：1872-6240
Prediction of the initiation of cerebral aneurysms -Progress over view FY2015- 査読有り

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

Proc 2nd Int Symp Multidiscipl Comput Anat　A03-KB001　2016年
Transient middle cerebral artery occlusion in mice induces neuronal expression of RNF213, a susceptibility gene for moyamoya disease 査読有り

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

BRAIN RESEARCH　1630　50-55　2016年1月

DOI： 10.1016/j.brainres.2015.10.055 　

ISSN：0006-8993

eISSN：1872-6240
Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation 査読有り

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年1月

DOI： 10.1002/stem.2206 　

ISSN：1066-5099

eISSN：1549-4918
Difference in Transcranial Doppler Velocity and Patient Age between Proximal and Distal Middle Cerebral Artery Vasospasms after Aneurysmal Subarachnoid Hemorrhage. 国際誌査読有り

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年

DOI： 10.1159/000447330 　

詳細を見る詳細を閉じる

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.
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 査読有り

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年

DOI： 10.1155/2016/2386031 　

ISSN：1748-670X

eISSN：1748-6718
Risk factors for meningitis after craniotomy in patients with subarachnoid hemorrhage due to anterior circulation aneurysms rupture 査読有り

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

CLINICAL NEUROLOGY AND NEUROSURGERY　139　302-306　2015年12月

DOI： 10.1016/j.clineuro.2015.10.029 　

ISSN：0303-8467

eISSN：1872-6968
増大傾向を示した小型中大脳動脈(M1)動脈瘤の1例査読有り

藤村幹, 新妻邦泰, 冨永悌二

脳神経外科ジャーナル　24　(12)　878-882　2015年12月

DOI： 10.7887/jcns.24.878 　
Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities 査読有り

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

BRAIN RESEARCH　1629　318-328　2015年12月

DOI： 10.1016/j.brainres.2015.10.039 　

ISSN：0006-8993

eISSN：1872-6240
Immuno-Northern Blotting: Detection of RNA Modifications by Using Antibodies against Modified Nucleosides 査読有り

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年11月

DOI： 10.1371/journal.pone.0143756 　

ISSN：1932-6203
Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients with Ruptured Supraclinoid Internal Carotid Artery Aneurysms 査読有り

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

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

DOI： 10.1016/j.jstrokecerebrovasdis.2015.06.028 　

ISSN：1052-3057

eISSN：1532-8511
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 査読有り

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年10月

DOI： 10.1016/j.brainres.2015.07.039 　

ISSN：0006-8993

eISSN：1872-6240
Use of actuator-driven pulsed water jet in brain and spinal cord cavernous malformations resection 査読有り

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

Clinical Neurosurgery　11　394-403　2015年9月1日
出版者・発行元： Lippincott Williams and Wilkins
DOI： 10.1227/NEU.0000000000000867 　

ISSN：0148-396X 0069-4827
Use of Actuator-Driven Pulsed Water Jet in Brain and Spinal Cord Cavernous Malformations Resection 査読有り

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

OPERATIVE NEUROSURGERY　11　(3)　394-403　2015年9月

DOI： 10.1227/NEU.0000000000000867 　

ISSN：2332-4252
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 査読有り

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

NEUROLOGIA MEDICO-CHIRURGICA　55　(10)　813-817　2015年9月

DOI： 10.2176/nmc.cr.2015-0052 　

ISSN：0470-8105

eISSN：1349-8029
Ruptured Cerebral Microaneurysm Diagnosed by 3-Dimensional Fast Spin-Echo T1 Imaging with Variable Flip Angles 査読有り

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年8月

DOI： 10.1016/j.jstrokecerebrovasdis.2015.04.031 　

ISSN：1052-3057

eISSN：1532-8511
Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia 査読有り

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

JOURNAL OF NEUROSURGERY　123　(1)　243-253　2015年7月

DOI： 10.3171/2014.9.JNS14778 　

ISSN：0022-3085

eISSN：1933-0693
経過観察中に破裂した未破裂脳動脈瘤症例に関する検討査読有り

小山新弥, 井上瑞穂, 内田浩喜, 新妻邦泰, 斉藤敦志, 昆博之, 佐々木達也, 西嶌美知春

脳神経外科　43　(6)　523-529　2015年6月10日

DOI： 10.11477/mf.1436203064 　
もやもや病に対する血行再建術後過灌流に対するミノサイクリンを用いた周術期管理の現状と問題点査読有り

藤村幹, 新妻邦泰, 遠藤英徳, 佐藤健一, 井上敬, 冨永悌二

脳卒中の外科　43　(2)　136-140　2015年3月
出版者・発行元： (一社)日本脳卒中の外科学会
DOI： 10.2335/scs.43.136 　

ISSN：0914-5508

eISSN：1880-4683
Quantitative analysis of early postoperative cerebral blood flow contributes to the prediction and diagnosis of cerebral hyperperfusion syndrome after revascularization surgery for moyamoya disease 査読有り

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

NEUROLOGICAL RESEARCH　37　(2)　131-138　2015年2月

DOI： 10.1179/1743132814Y.0000000432 　

ISSN：0161-6412

eISSN：1743-1328
Enhanced post-ischemic angiogenesis in mice lacking RNF213; a susceptibility gene for moyamoya disease 査読有り

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年1月

DOI： 10.1016/j.brainres.2014.11.014 　

ISSN：0006-8993

eISSN：1872-6240
動脈硬化性変化をきたした未破裂脳動脈瘤5例の検討査読有り

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年12月
出版者・発行元：サノフィ(株)仙台オフィス
ISSN：1880-9278
Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility gene 査読有り

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

NEUROREPORT　25　(18)　1442-1446　2014年12月

DOI： 10.1097/WNR.0000000000000289 　

ISSN：0959-4965

eISSN：1473-558X
Maximum Preservation of the Media in Carotid Endarterectomy 査読有り

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

NEUROLOGIA MEDICO-CHIRURGICA　54　(10)　812-818　2014年10月

DOI： 10.2176/nmc.tn.2014-0202 　

ISSN：0470-8105

eISSN：1349-8029
局所酸素飽和度、運動誘発電位、体性感覚誘発電位を用いた頸動脈内膜剥離術の術中モニタリング内シャントの必要性に関連して査読有り

小山新弥, 長南雅志, 新妻邦泰, 昆博之, 阿部誠, 松尾進太郎, 佐々木達也, 西嶌美知春

脳卒中の外科　42　(5)　340-346　2014年9月

DOI： 10.2335/scs.42.340 　
AVMに対する治療戦略 -血管内治療医の立場から- 査読有り

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年8月

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ISBN:0289-8438
SMTP-7, a new thrombolytic agent, decreases hemorrhagic transformation after transient middle cerebral artery occlusion under warfarin anticoagulation in mice 査読有り

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

BRAIN RESEARCH　1578　38-48　2014年8月

DOI： 10.1016/j.brainres.2014.07.004 　

ISSN：0006-8993

eISSN：1872-6240
Development of a de novo arteriovenous malformation after bilateral revascularization surgery in a child with moyamoya disease Case report 査読有り

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

JOURNAL OF NEUROSURGERY-PEDIATRICS　13　(6)　647-649　2014年6月

DOI： 10.3171/2014.3.PEDS13610 　

ISSN：1933-0707

eISSN：1933-0715
経過観察中に増大した80歳以上の未破裂脳動脈瘤に対する瘤内塞栓術－高齢者における塞栓術の注意点、工夫－査読有り

鈴木一郎, 松本康史, 新妻邦泰, 近藤竜史, 遠藤英徳, 藤原悟, 高橋明, 清水宏明, 冨永悌二

JNET: Journal of Neuroendovascular Therapy　8　(1)　14-20　2014年3月

DOI： 10.5797/jnet.or.13036 　

ISSN：1882-4072
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 査読有り

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年3月

DOI： 10.1016/j.brainres.2014.01.011 　

ISSN：0006-8993

eISSN：1872-6240
Minocycline Prevents Focal Neurological Deterioration Due to Cerebral Hyperperfusion After Extracranial-Intracranial Bypass for Moyamoya Disease 査読有り

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

NEUROSURGERY　74　(2)　163-170　2014年2月

DOI： 10.1227/NEU.0000000000000238 　

ISSN：0148-396X

eISSN：1524-4040
Hemodynamic analysis of intracranial aneurysms with atherosclerosis 査読有り

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

IFMBE Proceedings　43　738-740　2014年
出版者・発行元： Springer Verlag
DOI： 10.1007/978-3-319-02913-9_188 　

ISSN：1680-0737
60歳以上の高齢もやもや病患者に対する血行再建術－周術期過灌流に注目して－査読有り

藤村幹, 清水宏明, 井上敬, 新妻邦泰, 冨永悌二

脳卒中の外科　42　(1)　37-41　2014年1月

DOI： 10.2335/scs.42.37 　

ISSN：0914-5508
Cervical perimedullary arteriovenous shunts: A study of 22 consecutive cases with a focus on angioarchitecture and surgical approaches 査読有り

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

Neurosurgery　75　(3)　238-249　2014年
出版者・発行元： Lippincott Williams and Wilkins
DOI： 10.1227/NEU.0000000000000401 　

ISSN：1524-4040 0148-396X

eISSN：1524-4040
Signal changes on T2*-weighted magnetic resonance imaging from the acute to chronic phases in patients with subarachnoid hemorrhage 査読有り

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

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

DOI： 10.1159/000355897 　

ISSN：1015-9770 1421-9786

eISSN：1421-9786
Surgical Treatment of Spinal Extradural Arteriovenous Fistula With Parenchymal Drainage: Report on 5 Cases 査読有り

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

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

DOI： 10.1227/NEU.0000000000000189 　

ISSN：0148-396X

eISSN：1524-4040
Fusion imageを用いた前脈絡叢動脈の解剖学的variationの術前評価査読有り

青木靖子, 遠藤英徳, 新妻邦泰, 井上敬, 清水宏明, 冨永悌二

脳神経外科　41　(12)　1075-1080　2013年12月

ISSN：0301-2603 1882-1251

eISSN：1882-1251
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年11月
Relative Residence Time Prolongation in Intracranial Aneurysms: A Possible Association With Atherosclerosis 査読有り

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年11月

DOI： 10.1227/NEU.0000000000000096 　

ISSN：0148-396X

eISSN：1524-4040
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年9月
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年9月
急性硬膜下血腫を来した髄膜腫の1手術例査読有り

長南雅志, 新妻邦泰, 小山新弥, 昆博之, 三戸聖也, 黒滝日出一, 緑川宏, 佐々木達也, 西嶌美知春

Neurological Surgery 脳神経外科　41　(3)　235-239　2013年3月

ISSN：0301-2603 1882-1251
Concurrent dural and perimedullary arteriovenous fistulas at the craniocervical junction: Case series with special reference to angioarchitecture ; Clinical article 査読有り

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

Journal of Neurosurgery　118　(2)　451-459　2013年2月

DOI： 10.3171/2012.10.JNS121028 　

ISSN：0022-3085 1933-0693

eISSN：1933-0693
高齢者の症候性脳血管攣縮非高齢者との比較査読有り

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年2月
Pulsed-liquid jet surgical device: Evolution from shock/bubble interaction to clinical application 査読有り

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年
外傷性頭頚部血管障害のガイドライン ─病態，診断および治療法に関して─ 査読有り

佐々木達也, 長南雅志, 新妻邦泰, 小山新弥, 斉藤敦志, 昆博之, 西嶌美知春, 佐藤章

神経外傷　35　(2)　87-94　2012年12月30日
経過観察中に破裂した未破裂脳動脈瘤の検討査読有り

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年12月
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査読有り

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

神経外傷　35　(2)　141-146　2012年12月
血管内手術および直達手術で治療した幼児横静脈洞部硬膜動静脈瘻の1例査読有り

新妻邦泰, 坂田洋之, 小山新弥, 昆博之, 長南雅志, 佐々木達也, 西嶌美知春, 江面正幸, 冨永悌二

脳神経外科　40　(11)　1015-1020　2012年11月

ISSN：0301-2603 1882-1251
Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice 査読有り

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

BRAIN　135　(11)　3298-3310　2012年11月

DOI： 10.1093/brain/aws259 　

ISSN：0006-8950
Neural Stem Cells Genetically Modified to Overexpress Cu/Zn-Superoxide Dismutase Enhance Amelioration of Ischemic Stroke in Mice 査読有り

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

STROKE　43　(9)　2423-+　2012年9月

DOI： 10.1161/STROKEAHA.112.656900 　

ISSN：0039-2499
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年9月
出版者・発行元：青森県立中央病院
ISSN：0387-0138
Minocycline-Preconditioned Neural Stem Cells Enhance Neuroprotection after Ischemic Stroke in Rats 査読有り

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年3月

DOI： 10.1523/JNEUROSCI.5686-11.2012 　

ISSN：0270-6474
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年12月
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年11月
Consistent Injury to Medium Spiny Neurons and White Matter in the Mouse Striatum after Prolonged Transient Global Cerebral Ischemia 査読有り

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

JOURNAL OF NEUROTRAUMA　28　(4)　649-660　2011年4月

DOI： 10.1089/neu.2010.1662 　

ISSN：0897-7151
Hemosiderin Detected by T-2*-Weighted Magnetic Resonance Imaging in Patients With Unruptured Cerebral Aneurysms: Indication of Previous Bleeding? 査読有り

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

NEUROLOGIA MEDICO-CHIRURGICA　51　(4)　275-281　2011年4月

DOI： 10.2176/nmc.51.275 　

ISSN：0470-8105
NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia 査読有り

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年3月

DOI： 10.1038/jcbfm.2010.166 　

ISSN：0271-678X
Transplanted Stem Cell-Secreted Vascular Endothelial Growth Factor Effects Poststroke Recovery, Inflammation, and Vascular Repair 査読有り

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年2月

DOI： 10.1002/stem.584 　

ISSN：1066-5099

eISSN：1549-4918
各種画像の三次元融合画像を用いた術前検討の有用性査読有り

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年12月

ISSN：1880-9278
Hemoglobin-Induced Oxidative Stress Contributes to Matrix Metalloproteinase Activation and Blood–Brain Barrier Dysfunction in vivo 査読有り

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

J Cereb Blood Flow Metab　30　(12)　1939-1950　2010年12月

DOI： 10.1038/jcbfm.2010.45 　

ISSN：0271-678X
Efficacy of Revascularization Surgery for Moyamoya Syndrome Associated With Graves' Disease 査読有り

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

NEUROLOGIA MEDICO-CHIRURGICA　50　(11)　977-983　2010年11月

DOI： 10.2176/nmc.50.977 　

ISSN：0470-8105
Reperfusion and Neurovascular Dysfunction in Stroke: from Basic Mechanisms to Potential Strategies for Neuroprotection 査読有り

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年6月

DOI： 10.1007/s12035-010-8102-z 　

ISSN：0893-7648
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年5月
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査読有り

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年12月

ISSN：1880-9278
CK2 Is a Novel Negative Regulator of NADPH Oxidase and a Neuroprotectant in Mice after Cerebral Ischemia 査読有り

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

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

DOI： 10.1523/JNEUROSCI.4161-09.2009 　

ISSN：0270-6474
Potential Role of PUMA in Delayed Death of Hippocampal CA1 Neurons After Transient Global Cerebral Ischemia 査読有り

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

STROKE　40　(2)　618-625　2009年2月

DOI： 10.1161/STROKEAHA.108.524447 　

ISSN：0039-2499
Transient global cerebral ischemia model in mice 査読有り

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年
出版者・発行元： Humana Press
DOI： 10.1007/978-1-60327-185-1_10 　
Middle cerebral artery plaque imaging using 3-Tesla high-resolution MRI 査読有り

Kuniyasu Niizuma, Hiroaki Shimizu, Shihomi Takada, Teiji Tominaga

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

DOI： 10.1016/j.jocn.2007.09.024 　

ISSN：0967-5868
Role of the p38 Mitogen-Activated Protein Kinase/Cytosolic Phospholipase A2 Signaling Pathway in Blood—Brain Barrier Disruption after Focal Cerebral Ischemia and Reperfusion 査読有り

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

J Cereb Blood Flow Metab　28　(10)　1686-1696　2008年10月

DOI： 10.1038/jcbfm.2008.60 　

ISSN：0271-678X
The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats 査読有り

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年10月

DOI： 10.1073/pnas.0806222105 　

ISSN：0027-8424
Induction of MMP-9 expression and endothelial injury by oxidative stress after spinal cord injury 査読有り

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

JOURNAL OF NEUROTRAUMA　25　(3)　184-195　2008年3月

DOI： 10.1089/neu.2007.0438 　

ISSN：0897-7151
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年11月13日

ISSN：0271-678X
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年11月13日

ISSN：0271-678X
Fiber Tracking法を用いた白質線維描出の問題点査読有り

新妻邦泰, 隈部俊宏, 清水宏明, 日向野修一, 高橋昭喜, 冨永悌二

脳神経外科ジャーナル　16　(6)　504-509　2007年6月

DOI： 10.7887/jcns.16.504 　

ISSN：0917-950X
Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome 査読有り

Kuniyasu Niizuma, Miki Fujimura, Toshihiro Kumabe, Tominaga Tominaga

JOURNAL OF CLINICAL NEUROSCIENCE　14　(1)　53-55　2007年1月

DOI： 10.1016/j.jocn.2005.09.021 　

ISSN：0967-5868
Surgical treatment of paraventricular cavernous angioma: Fibre tracking for visualizing the corticospinal tract and determining surgical approach 査読有り

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

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

DOI： 10.1016/j.jocn.2004.11.025 　

ISSN：0967-5868
Balloon test occlusionにおける局所脳酸素飽和度モニタリングの有用性査読有り

新妻邦泰, 上井英之, 松本康史, 近藤竜史, 清水宏明, 冨永悌二

脳神経外科　34　(7)　695-702　2006年7月

DOI： 10.11477/mf.1436100253 　

ISSN：0301-2603
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例査読有り

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

セラピューティック・リサーチ　26　(11)　2173-2177　2005年11月
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

脳神経外科　33　(8)　832-837　2005年8月
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の有用性査読有り

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年10月
膠芽腫と有鉤嚢虫症を合併したTurcot症候群の一例査読有り

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年5月
Exclusively extradural arteriovenous malformation with neurogenic claudication - Case illustration 査読有り

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

JOURNAL OF NEUROSURGERY　100　(4)　397-397　2004年4月

ISSN：0022-3085

︎全件表示 ︎最初の5件までを表示

MISC 103

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年6月
出版者・発行元：医歯薬出版(株)
ISSN： 0918-5259
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年
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年
ハイドロゲル-有機物を基材とする新規頭蓋内電極の安全性と有効性-医師主導治験による検証-

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年
【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年3月
出版者・発行元： (株)メディカ出版
ISSN： 0917-1495
神経系における幹細胞治療

新妻邦泰

BRAIN and NERVE　75　(2)　167-172　2023年2月

DOI： 10.11477/mf.1416202299 　
当科における小児脳血管障害の治療経験

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年

ISSN： 2435-824X
【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年8月
出版者・発行元：医歯薬出版(株)
ISSN： 0039-2359
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年4月
出版者・発行元： (一社)日本小児神経外科学会
ISSN： 0387-8023

eISSN： 2435-824X
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年3月
出版者・発行元： (一社)日本高次脳機能障害学会
ISSN： 1348-4818

eISSN： 1880-6554
【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年3月
出版者・発行元： (株)ライフメディコム
ISSN： 0287-8445
【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年3月
出版者・発行元： (株)メジカルビュー社
ISSN： 0286-5394
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年6月
出版者・発行元： (公社)日本補綴歯科学会
ISSN： 1883-4426

eISSN： 1883-6860
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年6月
出版者・発行元： (公社)日本補綴歯科学会
ISSN： 1883-4426

eISSN： 1883-6860
【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年6月
出版者・発行元： (一社)日本血栓止血学会
ISSN： 0915-7441

eISSN： 1880-8808
【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年4月
出版者・発行元： (株)北隆館
ISSN： 0919-8237
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年3月
出版者・発行元：日本神経心理学会
ISSN： 0911-1085

eISSN： 2189-9401
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年

ISSN： 2188-031X
麻酔薬の超選択的頭蓋内動脈による神経症状誘発は脳実質切除後の機能転帰を予測する

大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 新妻邦泰, 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年

ISSN： 2424-1709
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

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年

ISSN： 2424-1709
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年

ISSN： 0915-5902
【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年10月
出版者・発行元： (株)三輪書店
ISSN： 0914-4412
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年6月
出版者・発行元： (公社)日本補綴歯科学会
ISSN： 1883-4426

eISSN： 1883-6860
【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年5月
出版者・発行元： (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
専門医に求められる最新の知識脳血管障害脳梗塞に対する細胞治療の新展開招待有り

新妻邦泰

脳神経外科速報　30　(5)　498-505　2020年5月
出版者・発行元： (株)メディカ出版
ISSN： 0917-1495
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年2月
出版者・発行元： (株)ニュー・サイエンス社
ISSN： 1347-4340
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年
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年

ISSN： 2188-7519
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年

ISSN： 2188-7519
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, 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年
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年

ISSN： 2188-031X
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年
超選択的Wada testによる血管解剖と機能解剖の融合的評価

大沢伸一郎, 鈴木匡子, 浮城一司, 柿沼一雄, 上利大, 新妻邦泰, 神一敬, 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年
Muse細胞を用いたドナー細胞の点滴による神経再生医療の実現に向けて

出澤真理, 新妻邦泰, 冨永悌二

BRAIN and NERVE　71　(8)　895-900　2019年8月

DOI： 10.11477/mf.1416201372 　
【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年5月
出版者・発行元： (株)ライフ・サイエンス
ISSN： 0387-1088
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年

ISSN： 1882-0654
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年

ISSN： 2188-031X
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年

ISSN： 2424-1709
【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年1月
出版者・発行元： (株)医薬ジャーナル社
ISSN： 1344-6940
脳梗塞におけるMuse細胞を用いた治療戦略招待有り

新妻邦泰, 冨永悌二

血液フロンティア　29　(2)　47-57　2019年1月
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年12月
出版者・発行元：サノフィ(株)仙台オフィス
ISSN： 1880-9278
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年10月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401
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年9月12日
出版者・発行元： (一社)日本てんかん学会
ISSN： 0912-0890
【Hybrid Neurosurgeonのための疾患別臨床脳血管解剖テキスト】(第2章)開頭手術と血管内治療の複合治療 dAVF 横静脈洞 S状静脈洞部dAVF

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年9月
出版者・発行元： (株)メディカ出版
ISSN： 0917-1495
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年8月
出版者・発行元： (株)医学書院
ISSN： 0301-2603

eISSN： 1882-1251
【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年7月
出版者・発行元：日本脳神経外科コングレス
ISSN： 0917-950X
小児もやもや病診断・治療の進歩と長期予後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

The Mt. Fuji Workshop on CVD　36　1-4　2018年7月
出版者・発行元： (株)にゅーろん社
ISSN： 0289-8438
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年3月1日

ISSN： 0289-0585
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年

ISSN： 2424-1709
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年
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年
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年
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年

ISSN： 2188-7519
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年
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(J‐STAGE)　2018年

DOI： 10.7887/jcns.27.514 　

ISSN： 0917-950X
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119

eISSN： 2424-1709
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119

eISSN： 2424-1709
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年

ISSN： 2188-7519
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年
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119

eISSN： 2424-1709
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 2423-9119
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年11月
出版者・発行元： (一社)日本神経学会
ISSN： 0009-918X
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年10月
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年6月

DOI： 10.1007/s12035-010-8102-z 　

詳細を見る詳細を閉じる

First Online:17 February 2010
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年5月
出版者・発行元： (一社)日本血栓止血学会
ISSN： 0915-7441
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年2月
出版者・発行元： (一社)日本脳神経外傷学会
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072

eISSN： 2186-2494
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年10月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年10月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年9月
脳卒中専門医に必要な基本知識（９）無症候性脳血管障害

新妻邦泰, 冨永悌二

脳神経外科　43　(4)　357-368　2015年4月10日

DOI： 10.11477/mf.1436203022 　
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年12月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401

eISSN： 2188-7519
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401
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年11月
出版者・発行元：日本脳循環代謝学会
ISSN： 0915-9401
脳虚血後の神経細胞死におけるp53 依存的経路の役割

新妻邦泰, 冨永悌二

脳循環代謝　25　(2)　117-121　2014年11月
出版者・発行元： The Japanese Society of Cerebral Blood Flow and Metabolism
DOI： 10.16977/cbfm.25.2_117 　

ISSN： 0915-9401

詳細を見る詳細を閉じる

脳虚血後には種々の分子シグナリングの経路が活性化されるが，虚血の程度が強い場合には，アポトーシス関連経路が活性化されることになる．アポトーシス関連経路においてはp53 が重要な役割を果たし，転写依存的に多数のアポトーシス関連分子を活性化し，その結果としてBcl-2 ファミリーメンバーの相互作用を介してミトコンドリア膜間腔に存在するcytochrome c やapoptosis-inducing factor などが放出される．その後にcaspase-9，caspase-3 の活性化が続きアポトーシスを誘導するが，この「放出」のステップが不可逆的であるために，ここが細胞死を決定づける段階であると考えられている．本稿では，このステップを制御すると考えられるp53 依存性の分子とBcl-2 ファミリーのタンパクとの相互作用の中から，我々のグループが研究を重ねたBax, PUMA, PIDD を中心に概説する．
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年7月
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年6月
出版者・発行元： (株)メディカ出版
ISSN： 0917-1495
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年5月

DOI： 10.5853/jos.2014.16.2.65 　

ISSN： 2287-6391

eISSN： 2287-6405
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072

eISSN： 2186-2494
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年11月
出版者・発行元： (NPO)日本脳神経血管内治療学会
ISSN： 1882-4072

eISSN： 2186-2494
【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年4月

ISSN： 0289-0585
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年
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年
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年

ISSN： 0915-9401
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年

ISSN： 1882-4072
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年

ISSN： 0915-9401
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年12月
出版者・発行元： (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
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年

ISSN： 0915-9401
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年

ISSN： 0915-9401
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年1月

DOI： 10.1016/j.bbadis.2009.09.002 　

ISSN： 0925-4439
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年5月

DOI： 10.1111/j.1471-4159.2009.05897.x 　

ISSN： 0022-3042
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年

ISSN： 0915-9401
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年

ISSN： 0915-9401
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年

ISSN： 1347-9040
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年

ISSN： 1347-9040

︎全件表示 ︎最初の5件までを表示

書籍等出版物 5

Muse Cells: Endogenous Reparative Pluripotent Stem Cells (Advances in Experimental Medicine and Biology 1103)

新妻邦泰, Cesar V. Borlongan, 冨永悌二

Springer (Tokyo)　2018年12月

ISBN: 9784431568452
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年4月5日

ISBN: 9784840461474
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年6月1日

ISBN: 9784877941697
Magnetic Resonance Angiography Basics to Future

Kuniyasu Niizuma, Hiroaki Shimizu, Teiji Tominaga

InTech　2012年3月21日

ISBN: 9789535104018

詳細を見る詳細を閉じる

doi:10.5772/30536
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年10月3日

ISBN: 9781603271844

詳細を見る詳細を閉じる

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

講演・口頭発表等 64

脳梗塞に対するMuse細胞治療の開発招待有り

新妻邦泰

第21回泌尿器科再建再生研究会　2024年6月1日
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招待有り

新妻邦泰

第44回日本脳神経外科コングレス総会　2024年5月12日
Development of Stem Cell Therapy for Cerebral Infarction 招待有り

Kuniyasu Niizuma

Abu Dhabi 2024 International Brain & Spine Congress (ADNEURO 2024)　2024年4月28日
Development of Novel Thrombolytic and Neuroprotective Therapies for Acute Cerebral Infraction 国際会議招待有り

新妻邦泰

1st SSMC Anneual Neurosurgery Scientific Day　2024年4月25日
SMTPを用いた新規血栓溶解剤の開発と実用化に向けて招待有り

新妻邦泰

第49回日本脳卒中学会学術集会　2024年3月7日
脳腫瘍に対する光治療の可能性招待有り

計算メディカルサイエンスワークショップ2023　2023年12月11日
Development of Muse Cell Therapy for Ischemic Stroke 国際会議

East Asian Conference on Neurointervention (EACoN2023)　2023年11月26日
中枢神経疾患に対するMuse細胞治療招待有り

新妻邦泰

第66回日本脳循環代謝学会学術集会　2023年11月10日
脳梗塞に対するMuse細胞治療招待有り

新妻邦泰

第47回日本高次機能障害学会学術総会　2023年10月28日
中枢神経疾患に対するMuse細胞療法の開発招待有り

新妻邦泰

日本脳神経外科学会第82回学術総会　2023年10月25日
脳卒中・心臓病等総合支援センターモデル事業に関して招待有り

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年10月3日

詳細を見る詳細を閉じる

日本脳卒中学会認定脳卒中専門医認定3単位対象講演
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年9月30日
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年9月29日
脳梗塞に対するMUSE細胞治療～基礎から治験まで～招待有り

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年6月29日
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年5月31日
再生治療のフロンティア招待有り

新妻邦泰

第43回日本脳神経外科コングレス総会　2023年5月20日
脳梗塞に対するMuse細胞治療の開発招待有り

新妻邦泰

第128回日本解剖学会総会・全国学術集会　2023年3月19日
シーズ探索と実用化研究の取り組み招待有り

新妻邦泰

Stroke2023　2023年3月18日

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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～」
脳梗塞に対するMuse細胞治療招待有り

新妻邦泰

第52回日本脳卒中の外科学会学術集会　2023年3月16日
Development of stem cell-based therapy for ischemic stroke 国際会議招待有り

Kuniyasu Niizuma, Teiji Tominaga

The 10th Pan Pacific Neurosurgical Congress　2023年2月7日
脳梗塞亜急性期に対するMuse細胞治療招待有り

新妻邦泰

第52回小児神経学セミナー　2022年12月1日
脳梗塞に対するMuse細胞治療招待有り

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年10月28日
PNAS掲載への道のり招待有り

新妻邦泰

日本脳神経外科学会第81回学術総会　2022年9月28日
Development of Muse Cell Therapy for Ischemic Stroke 国際会議招待有り

Niizuma K, Tominaga T

10th Korea-Japan Joint Stroke Conference　2022年9月17日
脳梗塞に対する新規治療法開発への挑戦招待有り

新妻邦泰

第27回新潟神経疾患研究会　2022年9月8日

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新潟県医師会生涯教育講座／大学院特別講義
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－招待有り

新妻邦泰

第63回（一社）日本脳神経外科学会東北支部会　2022年9月3日
Development of a Futuristic Supporting System for Neuroendovascular Therapy 国際会議招待有り

Kuniyasu Niizuma

The 18th Interdisciplinary Cerebrovascular Symposium (ICS2022)　2022年8月27日
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招待有り

新妻邦泰

第22回日本分子脳神経外科学会　2022年7月23日
Application of Muse Cell Therapy to Stroke 国際会議招待有り

Niizuma K, Tominaga T

The 30th International Symposium on Cerebral Blood Flow, Metabolism and Function (BRAIN & BRAIN PET 2022)　2022年6月1日
くも膜下出血後脳血管攣縮治療の現在とICU 管理の今後招待有り

新妻邦泰

第42回日本脳神経外科コングレス総会　2022年5月14日
新規脳梗塞治療薬SMTPの開発と臨床への橋渡し招待有り

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年11月27日
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招待有り

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年10月27日
新規脳梗塞治療薬SMTPの開発招待有り

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年10月27日
Development of a digital supporting system for neuroendovascular therapy 国際会議招待有り

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年9月10日
NIRSの臨床的有用性～脳神経外科の観点から考える～招待有り

新妻邦泰

第68回日本麻酔科学会年次学術集会　2021年6月3日
脳梗塞に対する新規治療の開発招待有り

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年5月16日
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年3月13日
Muse細胞を用いた新規脳梗塞治療の開発招待有り

新妻邦泰

第46回日本脳卒中学会学術集会　2021年3月11日
Optimal Model to Advanced Cell-based Therapy 国際会議招待有り

Kuniyasu Niizuma

Asia Pacific Stroke Conference 2020　2020年12月6日
中枢神経疾患に対する新規細胞治療の開発招待有り

新妻邦泰

第63回日本脳循環代謝学会学術集会　2020年11月13日
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年11月6日
脳梗塞に対する幹細胞治療の基礎から臨床への橋渡し招待有り

新妻邦泰

日本脳神経外科学会第79回学術総会　2020年10月15日
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－招待有り

新妻邦泰, 冨永悌二

第18回日本臨床医療福祉学会　2020年10月10日
Muse細胞による神経再生医療の開発招待有り

新妻邦泰

第44回日本神経心理学会学術集会　2020年10月1日
Muse cell treatment for cerebral ischemia 招待有り

新妻邦泰

第61回日本神経学会学術大会　2020年9月1日
新規脳梗塞治療薬SMTPの開発招待有り

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年8月25日
脳虚血に対する橋渡し研究招待有り

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年8月12日
脳動脈瘤に対する治療医シミュレーション・再発予測招待有り

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年1月24日
脳梗塞治療の INNOVATION～東北大学における取り組み～招待有り

新妻邦泰

第62回日本脳循環代謝学会学術集会　2019年11月29日
血管内治療支援装置の開発招待有り

新妻邦泰

第62回日本脳循環代謝学会学術集会　2019年11月29日
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年11月23日
脳梗塞に対する新規治療法の開発招待有り

新妻邦泰

第59回日本臨床化学会年次学術集会　2019年9月29日
脳梗塞に対する Muse 細胞治療の開発招待有り

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年9月12日
Muse細胞による再生医療について招待有り

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年8月3日
A novel model of cerebral hyperperfusion with blood brain barrier breakdown, white matter injury, and cognitive dysfunction 国際会議

The 29th International Symposium on Cerebral Blood Flow, Metabolism and Function (BRAIN & BRAIN PET 2019)　2019年7月7日
Muse 細胞を用いた再生医療～脳梗塞新規治療の開発～招待有り

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年4月29日

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アカデミックレクチャー
Muse Cell Transplantation to Treat Cerebral Ischemia 国際会議招待有り

The 14th Korea-Japan Joint Conference on Surgery for Cerebral Stroke (14KJJC)　2019年4月27日
脳梗塞に対するMuse細胞治療の開発招待有り

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年4月13日
Muse細胞を用いた脳梗塞医再生治療招待有り

新妻邦泰

第44回日本脳卒中学会学術集会　2019年3月22日
Muse細胞による脳梗塞治療招待有り

新妻邦泰

第18回日本再生医療学会総会　2019年3月21日
アプリで参加！君の診断は？招待有り

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年11月22日
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細胞治療招待有り

新妻邦泰

日本脳神経外科学会第77回総会　2018年10月11日
Muse細胞による脳梗塞治療招待有り

新妻邦泰

日本脳神経外科学会第77回総会　2018年10月10日
Muse細胞による脳梗塞治療招待有り

新妻邦泰

第43回脳卒中学会学術集会　2018年3月17日

︎全件表示 ︎最初の5件までを表示

産業財産権 5

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

産業財産権の種類: 特許権
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

産業財産権の種類: 特許権
毛髪損傷の治療剤

新妻邦泰, 冨永悌二

産業財産権の種類: 特許権
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

産業財産権の種類: 特許権
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

産業財産権の種類: 特許権

共同研究・競争的資金等の研究課題 40

次世代光技術を用いた革新的脳腫瘍制御法の創発競争的資金

新妻邦泰

2023年4月～ 2030年3月
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

2024年6月28日～ 2027年3月31日
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

2024年4月1日～ 2027年3月31日
S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発

伊藤明, 新妻邦泰, 遠藤英徳

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2024年4月1日～ 2027年3月31日
血液脳関門模擬チップと計測融合シミュレーションの統合による血管透過性制御法の創成

船本健一, 立川正憲, 新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2023年4月1日～ 2027年3月31日
内皮-平滑筋相互作用におけるRNF213の役割ともやもや病発症機序解明

新妻邦泰, Rashad Sherif, 菅野新一郎, 森戸大介, 豊原敬文, 阿部高明, 坂田洋之

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (A)

研究機関：Tohoku University

2023年4月1日～ 2026年3月31日
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

2023年4月1日～ 2026年3月31日
マイクロ波による経頭蓋全脳熱音響イメージング

西條芳文, 新妻邦泰, 安藤晃

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2023年4月1日～ 2026年3月31日
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

2023年4月1日～ 2026年3月31日
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

2023年4月1日～ 2026年3月31日
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

2023年4月1日～ 2026年3月31日
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

2021年4月1日～ 2026年3月31日

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今年度は、まずバイオマーカーによる神経損傷程度推定法を検討した。脳主幹動脈閉塞例に対し、急性期血行再建術を施行した症例を対象とした。神経損傷バイオマーカーとしては、研究者らがこれまで報告してきたtRNA由来物を測定した。脳神経損傷程度はこれまでMRI拡散強調像で評価されることが一般的であった。しかし、MRI拡散強調像では、すでに非可逆的な損傷を受けていても、所見として捉えることができない偽陰性症例や、その逆に可逆的損傷にもかかわらず、所見が出現する偽陽性の症例が存在する。本研究では、拡散強調画像を取得するタイミングで採血した血漿からtRNA由来物を定量的に測定した。神経損傷は３ヶ月後の神経学的検査で判定することとした。その結果、tRNA由来物はMRI拡散強調像よりも鋭敏に神経損傷を評価できることが判明した。この結果は現在英文誌に投稿中である。さらに、AIによる神経機能評価法の基礎的な検討も始めた。AIによるdeep learning はこれまでの統計学的手法では抽出困難な危険因子を同定できる可能性がある。しかし、deep learningでは古典的統計学的手法に比べ、必要症例数が飛躍的に増加する。脳循環予備能推定が本研究の最終目標であるが、本年度はまずは十分な症例数のある疾患でAIによる神経機能評価法を確認した。対象としては慢性硬膜下血腫手術例約200例を対象とした。統計学的手法では術後神経機能回復が遅れる危険因子として、年齢・術前意識レベルなどが抽出された。AIを用いた検討では、これら以外にリハビリテーションの有無が、術後神経機能回復と関係があることが示唆された。統計学的手法ではリハビリテーションの有無は交絡因子とされたが、AIでの検討では独立因子と判定された。今後はさらに症例数を増やすことにより、どちらがより臨床的に有効か研究を続けたい。
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

2022年6月30日～ 2025年3月31日
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

2022年4月1日～ 2025年3月31日
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

2022年4月1日～ 2025年3月31日
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

2022年4月1日～ 2025年3月31日
血流と内皮細胞の相互作用から迫るもやもや病の発症機序解明

冨永悌二, 藤村幹, Rashad Sherif, 新妻邦泰, 森戸大介, 下田由輝

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

研究種目：Grant-in-Aid for Scientific Research (A)

研究機関：Tohoku University

2021年4月5日～ 2024年3月31日

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もやもや病は両側内頚動脈終末部が進行性に狭窄・閉塞し、付近に異常血管網の発達を認める原因不明の疾患であり、病態解明と新規治療開発が求められている。もやもや病の感受性遺伝子であるRNF213遺伝子が同定されたが、その変異単独でもやもや病は発症せず、それに加えて何らかの二次的因子が加わり発症するtwo hit theoryが提唱されている。本研究の目的は、今までに明らかではなかった血流と血管内皮細胞の相互作用という切り口から、もやもや病の病因・病態を解明することである。本年度は①～⑤の5つの要素に分けて研究を行った。 ①数値流体力学的解析（CFD解析）：もやもや病患者においてどのように血液が流れ、血管壁にはどのような力がかかるのかをCFDを用いて解析したが、もやもや病の血管形態には個人差も大きく、未だまとまった形の知見は得られていない。 ②流体培養を用いた解析：「流れ」の違いに応じて血管内皮細胞においてRNF213遺伝子発現が変化することが見いだされた。 ③免疫学的解析：RNF213遺伝子変異により抗原取り込みや処理が遅延することを明らかにした。 ④ 臨床応用につながるバイオマーカー探索：RNF213遺伝子変異マウスを用いて、バイオマーカー候補を探索中である。臨床例では、RNF213遺伝子変異がもやもや病患者において肺動脈狭窄を合併する危険因子である可能性が見いだされ、論文として報告した。 ⑤RNF213に関する解析：RNF213変異体の新たな遺伝子変異マウスが樹立されたため、それを用いた実験を行うための環境を構築した。上記のようにそれぞれの要素につき研究の進捗を認めるが、最終目標であるもやもや病の病因解明には未だ至ってはいない。
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

2021年4月1日～ 2024年3月31日

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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。
認知症に対するMuse細胞による革新的治療法の開発

新妻邦泰, 冨永悌二, Rashad Sherif, 坂田洋之, 伊藤明

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2020年4月1日～ 2023年3月31日

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本邦では、高齢化と共に認知症患者が急増しており、患者および家族の生活の質の低下、あるいは医療費や介護費用などの問題から大きな社会問題となっている。しかしながら、認知症に対する根本治療は未だ存在しない。Muse細胞は生体に存在する自然の多能性幹細胞であり、腫瘍性形成リスクが低い。安全性と組織修復性を両立していると考えられる細胞で、幹細胞治療の有力なソースとして注目されている。我々は脳梗塞動物モデルにおいてMuse細胞が生着、分化し神経回路を再建することを示してきたが、認知症においても脳梗塞と同様にMuse細胞による修復・機能再建が得られる可能性があると考えられる。本研究の目的は、認知症に対するMuse細胞治療を開発するため、非臨床POCを取得することである。Muse細胞治療により失われた認知機能を回復させることが出来れば、要介護者の減少、患者及び家族の生活の質の向上、医療費削減等、きわめて大きな社会的波及効果が生じると考えられる。本年度も両側総頚動脈閉塞によるラット慢性虚血モデルを用いて認知機能障害を誘導し、それに対して細胞治療を行うことにより、以下の各種項目につき治療効果の有無や安全性の問題の有無につき検証した。Barnes mazeを用いた認知機能の評価、炎症細胞やアポトーシスの減少の有無、血管新生や細胞生着についての評価、細胞投与による副作用と考えられるような腫瘍形成の有無、異所性生着の有無。細胞治療による認知機能改善効果が示唆され、血管新生や神経組織保護などがメカニズムの一部として考えられた。また安全性上の問題となるような所見も認めなかった。
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

2020年4月1日～ 2023年3月31日

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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。、
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

2020年4月1日～ 2023年3月31日

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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。
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

2020年4月1日～ 2023年3月31日

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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。
もやもや病感受性遺伝子ＲＮＦ２１３多型保持健常者における潜在的画像所見のＡＩ解析

園部真也, 冨永悌二, 藤村幹, 中川敦寛, 新妻邦泰, 麦倉俊司

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2020年4月1日～ 2023年3月31日

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・研究の遂行について倫理委員会の承認を得た。・研究に使用するデータの利用許可を得た。また研究に使用するデータの大部分について利用準備を完了した。・研究の手法についてより詳細な吟味を行った。具体的には、研究の核を成す「血管の信号を解剖学的な理解に基づいて正確に抽出する」ことと「血管形状を数値に変換し各種のパラメーターを取り出す」ことについて手法を洗練した。それぞれについて分けて以下に記載する。・「血管の信号を解剖学的な理解に基づいて正確に抽出する」過程については、当初の研究計画では血管の信号を平面へ投射して計測する方法を予定していたが、平面へ投射せず立体的な位置関係を維持したまま信号を処理する方法が新たに考案された。後者の方がより正確に血管形状を数値化できることが判明したため、後者の手法を用いることとした。・「血管形状を数値に変換し各種のパラメーターを取り出す」過程について、試行錯誤を重ねた。様々な既存のモデルやアルゴリズムを試したが、それぞれ一長一短があり、血管形状の個人差に対応しきれないことによる不具合が存在することが判明した。特に、血管の走行に垂直な断面で血管を観察した際に正円でない場合（扁平な血管であるため断面が楕円の場合や狭窄を伴う血管であるため断面が不整形の場合）においてこれらの不具合が顕著であり、これを解決するような新しいモデルとアルゴリズムを有するプログラムの開発に着手した。同プログラムの開発について、およそ八割程度の達成が得られた。
Muse細胞を用いた脊髄損傷に対する新しい細胞移植治療法の開発

遠藤俊毅, 新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2019年4月1日～ 2022年3月31日

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本研究の目的は、多能性幹細胞 Multilineage-differentiating stress enduring cell（以下Muse細胞）を用いた脊髄損傷に対する新しい細胞移植治療法の開発である。Muse細胞は東北大学で発見された多能性幹細胞であり、腫瘍形成能をもたず、安全性が高い。またMuse細胞は、血管内に投与されると傷害部位を認識して遊走し、生着、そして自発的に分化、組織修復と神経機能改善に貢献する特徴を有している。本研究は、ラット脊髄損傷モデルにたいしてヒト骨髄由来Muse細胞を使用してその移植治療効果を確認するはじめての実験である。さらに、多くの移植実験で従来行われてきたように、Muse細胞を脊髄損傷局所に投与するだけでなく、Muse細胞を経静脈投与し、Muse細胞が損傷脊髄内に到達し神経細胞に分化、さらに脊髄損傷後の神経機能回復につながるかどうかを評価する。これまでに脊髄損傷モデルの確立、ヒト骨髄幹細胞の培養と選択により、ヒトMuse細胞移植株を安定して得られるようになっている。これをもちいて、本研究では、脊髄損傷モデルを作成し、脊髄を露出して髄内にMuse細胞を直接投与する局所投与を行い、治療効果を確認している。さらに、脊髄損傷後にMuse細胞を経静脈投与する全く新しい治療方法を確立するための研究も開始している。本研究おいて、ラットの脊髄神経機能の改善効果を評価し、とくに、静脈投与によるより安全で低侵襲のMuse細胞移植治療法が確立されれば画期的である。
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

2019年4月1日～ 2022年3月31日

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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。
新規慢性脳虚血および脳血管内皮機能障害モデルの開発と血流再建後過灌流機序の解明

清水宏明, 新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Akita University

2018年4月1日～ 2021年3月31日

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雌ラットを用い、両側卵巣摘出によるエストロゲン枯渇と両側腎動脈後枝結紮＋食塩負荷による高血圧を惹起、1-3週後に総頚動脈を一側は結紮し、他側は高度狭窄とすることで慢性虚血を作成、その3日後に狭窄を解除することで生じる過灌流をlaser speckle flowmetry (LSF)で経時的に観察した。初年度の実験で、総頚動脈の一側閉塞、一側狭窄の3日後に狭窄を解除するとLSFで主に両側大脳脳血流上昇が確認できたが、血流上昇の程度には個体差が大きかった。LSFでの脳血流定量化の誤差と、ラットの全身あるいは頭部LSF観察部の状態によるばらつきを考えた。そこで今年度は、両側大脳の頭蓋骨開窓部を小さくするほか、小脳上にも開窓部を設けこれに対する比をとることとした。N=20ほどの個体で実験をおこなったが、一個体あたりの全経過が長いためか、途中死亡するものが未だ多く、解析に使用できると思われたのはN=6の個体のデータであった。LSFの定性画像では、頚動脈閉塞/狭窄による両側大脳虚血と、3日後の再開通後の両側大脳血流増加がみられていた。現在定量的に解析するためデータを採取している。
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, 中川敦寛, 新妻邦泰, 西嶌泰生

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2018年4月1日～ 2021年3月31日

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令和元年度に得た成果：光脳内けいれん誘発モデルの誘発回数と神経細胞脱落の関係について最適化をはかり、Muse細胞投与時期の検討を行った。昨年度に従来報告していたTGラット（Wister ratに対する遺伝子導入）よりも遺伝背景をLong-evansへ変更したTG ラットの方が実験効率（繁殖効率、実験時操作性）が良いことを発見し、以後同動物を使用している。①Muse細胞投与後の変化に対するコントロールとして、けいれん後に脳内細胞数もしくは生化学パラメータがどの程度変化するのかを検討した（海馬内の各解剖学的分画において神経細胞数およびTUNEL, NeuN, GFAP陽性率の変化）。②けいれん後のMuse細胞を投与による効果を検証するため、けいれん誘発後のMuse細胞投与（1.0x105個/ 個体, 1,3,7,14 day）を行い、細胞生着が確認された。ただし行動実験（Barnes circle maze test）ではコントロールに比して成績が良い傾向にあるものの有意差はなく、よりけいれんパラメータ（誘発回数およびけいれん持続時間、組織学的な損傷度合い）を検討してMuse細胞治療の投与法最適化を図っている。③当科の別実験においてMuse細胞は投与後3-6ヶ月でrejectionされることが証明されており（未発表）、免疫抑制による脳内生存期間の延長と機能改善の比較実験を進行している。現状で当初予定していた実験計画を概ね達成していると考えている。今後の研究計画：上記の実験を通して、ある程度細胞治療が効く病態が推測されるようになった。よりけいれんの重症度が高く、より急性期に投与する方が効果が高い可能性があり、それを実証するべく実験を継続していきたい。さらに慢性電極留置による長期脳波記録を実現し、将来的にはMuse細胞投与によるてんかん原性獲得の抑制機序の解析へ進めていきたい。
未破裂脳動脈瘤の増大に決定的な役割を果たす血行力学的因子の解明

杉山慎一郎, 新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2018年4月1日～ 2021年3月31日

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本研究の目的は、未破裂脳動脈瘤の増大に決定的な役割を果たしている「血行力学的因子」の解明である。数値流体力学（computational fluid dynamics: CFD）を用いて脳動脈瘤への流入血流量および瘤内の血液滞留時間を算出し、それらと脳動脈瘤増大速度との相関関係を検証する。本年度の研究実績として、以下の二つが挙げられる。一つ目は、脳動脈瘤内の血液滞留時間に関する新しい可視化方法の提示、二つ目は、脳動脈瘤内の血液滞留時間と脳動脈瘤壁における石灰化との関係性の証明である。従来、CFDを用いた脳動脈瘤の血行動態に関する研究においては、大きく二つの可視化手法が用いられてきた。一つは、脳動脈瘤内の流れ場を可視化する際に用いられる、「速度で色付けされた流線」であり、もう一つは、脳動脈瘤壁が血流から受ける「壁面せん断応力の等高線図」である。我々は、「血液滞留時間で色付けされた流線」および脳動脈瘤内腔面近傍における「血液滞留時間の等高線図」を作成することで、血液滞留時間によって一元的に脳動脈瘤の血行動態を評価する有用性を提案した。さらに、その可視化手法を用い、血液滞留時間が大型脳動脈瘤における石灰化部位の予測因子であることを発見した。脳動脈瘤壁における石灰化は動脈硬化性変化に伴うものである。我々は先行研究において、血液滞留時間の延長と脳動脈瘤壁における動脈硬化性変化との相関について報告したが、それを支持する成果であった。以上の結果を用いれば、CFDを用いた血行動態解析によって、脳動脈瘤が増大しにくい部位を識別できる可能性が高いものと考えられる。
Muse細胞を用いた中枢神経治療のための研究基盤構築

冨永悌二, 藤村幹, 新妻邦泰, 出沢真理, 後藤昌史, 坂田洋之

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

研究種目：Grant-in-Aid for Scientific Research (A)

研究機関：Tohoku University

2017年4月1日～ 2020年3月31日

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Muse細胞は生体に存在する自然の多能性幹細胞であり、腫瘍性を持たない。安全性と組織修復性を両立した珍しい細胞であり、幹細胞治療の有力なソースとして注目されている。本研究の目的は、寝たきりの大きな原因で、社会的問題となっている中枢神経疾患に対し、Muse細胞による局所修復・機能再建治療を幅広く開発する研究基盤を形成することである。Muse細胞製剤を開発中の株式会社Clioともすでに研究協力体制にある。Muse細胞治療により失われた神経機能を回復することにより、寝たきり患者の減少、患者及び家族の生活の質の向上、医療費削減等においてきわめて大きな社会的波及効果が生じると考えられる。
数値流体力学に基づく脳動脈瘤血流解析・リスク評価システムの構築

新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

研究種目：Grant-in-Aid for Young Scientists (A)

研究機関：Tohoku University

2017年4月1日～ 2020年3月31日

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本研究の目的は、数値流体力学的（以下、CFD）解析を用い、脳動脈瘤を中心とする脳血管障害について血流解析を行うことで、診断・治療の理論的根拠を確立すること、さらに、その過程で、血行力学的因子を含む症例レポジトリを構築することである。複数施設からの症例を解析し、脳動脈瘤コイル塞栓を行った症例、あるいはフロー大バーターで治療した症例を解析し、治療後の再発リスクなどの詳細を解析した。また、モヤモヤ病においてはその複雑な血行動態の一部を明らかにした。また、学会と連携し、症例登録、解析のシステムを構築した。
重症型もやもや病に対する多能性幹細胞Museを用いた血管新生療法の開発

藤村幹, 冨永悌二, 新妻邦泰, 坂田洋之

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2017年4月1日～ 2020年3月31日

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マウス/ラットに対する慢性脳虚血モデルを確立し、間接血行再建術を追加することにより側頭筋から脳表に向かう血管新生と免疫担当細胞の集積を確認した。もやもや病患者におけるM2マクロファージ関連因子sCD163・自己免疫関連マーカーCXCL5の発現上昇を見出し、もやもや病における免疫異常を報告した（Fujimura et al. Brain Res 2018）。もやもや病患者クモ膜に免疫組織染色を行い内因性多能性幹細胞の顕著な遊走を見出した。一方、実際の慢性虚血脳に対する間接血行再建術におけるにMuse細胞移植実験からは予想された有意な結果が得られず今後の検証が必要と考えられた。
多能性幹細胞(Muse細胞)による脳深部白質梗塞に対する白質再建

坂田洋之, 冨永悌二, 出澤真理, 渡辺みか, 藤村幹, 中川敦寛, 新妻邦泰

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

研究種目：Grant-in-Aid for Young Scientists (A)

研究機関：Tohoku University

2015年4月1日～ 2018年3月31日

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間葉系幹細胞中の一分画であるMuse 細胞は、高い神経分化能を持つ一方で腫瘍化の危険性は低く、優れた移植ソースと期待される。マウスを用いた本研究では、Muse細胞を移植することにより、脳梗塞によって破壊された神経回路が再建され、脳梗塞後の後遺障害が回復することが証明された。また、Muse細胞移植後に腫瘍形成等の合併症は見られず、長期的な安全性についても確認された。本研究成果が将来的に臨床応用されれば、脳梗塞患者の生活の質の向上及び寝たきりの患者数減少につながる可能性がある。
頚部内頚動脈のプラーク性状についての流体力学的研究

斉藤敦志, 新妻邦泰, 杉山慎一郎

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2015年4月1日～ 2018年3月31日

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Computational fluid dynamics(CFD)の手法を用いて、脳血管障害の疾患における、臨床上の有用性について研究を行った。当初は、頸動脈プラークを対象としたが、サンプルの集積が困難な状況となったため、脳動脈瘤を研究対象とした。未破裂脳動脈瘤をCFD解析の対象として研究を行い、増大を認めた未破裂脳動脈瘤においては、脳動脈瘤表面において、wall shear stress(WSS)とoscillatory shear index(OSI)の差が大きい領域を広く含む傾向が認められた。WSSとOSIの差は、動脈瘤の増大傾向の予測に有用な可能性が示唆された。
局所薬剤送達方法-CED法を駆使した脊髄損傷に対する新規治療方法の開発

杉山慎一郎, 遠藤俊毅, 新妻邦泰, 船本健一, 坂田洋之

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2015年4月1日～ 2018年3月31日

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脊髄損傷は、現代の医療においても治療が難しい。その理由の一つとして、脊髄には血液-脳脊髄関門があり、十分な量の薬を投与することが難しいことが挙げられる。この研究では、convection-enhanced delivery（CED）法という新しい薬剤投与方法を脊髄に応用することで、脊髄損傷部位に十分な薬を投与することに成功し、従来の薬物治療ん勝る治療効果が得られることを証明した。さらに、脊髄損傷に対するMuse細胞（multilineage-differentiating stress enduring cell）を用いた幹細胞治療についても、その効果を検証した。
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

2015年4月1日～ 2017年3月31日

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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。
数値流体力学解析に基づく脳動静脈奇形の血流解析と集学的治療への応用

清水宏明, 冨永悌二, 新妻邦泰, 杉山慎一郎, 鷲尾利克, 大田英揮, 荒船龍彦, 船本健一

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Akita University

2014年4月1日～ 2017年3月31日

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未破裂脳動静脈奇形に対して、脳血管撮影のデータから数値流体力学（CFD）解析を行った。合わせて、4次元MRIを行い、CFD、4次元MRIともに、十分な分解能をもって流速、wall shear stressなどの血行力学的パラメータが得られた。ただし、出血発症の脳動脈奇形が多かったことなどから十分な症例が集まらず、当初予定したような多数例でのデータベース作成は叶わなかった。一方、本研究組織においては、協力基盤を強固に形成できた。それを基に、別疾患ではあるが脳動脈瘤における新規ソフトウェア医療機器開発にまでプロジェクトが発展し、全体としては今後のCFD発展むけ、有意義な成果が得られた。
もやもや病における多能性幹細胞MUSE細胞を用いた血管新生療法の開発

藤村幹, 冨永悌二, 新妻邦泰, 坂田洋之

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2014年4月1日～ 2017年3月31日

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もやもや病に対する間接血行再建術における多能性幹細胞MUSE細胞を用いた血管新生促進の概念実証を目的に検討を行った。げっ歯類に対して慢性脳虚血誘導を行いもやもや病に類似した病態を作成した。そして間接血行再建術を施し、側頭筋から虚血脳に向かう血管新生と血管新生因子発現を確認した。さらに疾患感受性遺伝子RNF213変異マウスを用いたもやもや病の病態解明を行った。慢性脳虚血と間接血行再建術モデルを用いて血管新生が再現性をもって誘導可能となった。MUSE細胞については培養ヒト間葉系幹細胞に対して、SSEA-3/CD105抗体を用いたMACSによる分離を行い効率良いMUSE細胞の分離方法を確立した。
根治性と機能温存を両立する新規脳動脈解離治療用ステントの開発

遠藤英徳, 杉山慎一郎, 新妻邦泰, 仲井正昭, 中川敦寛

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

研究種目：Grant-in-Aid for Young Scientists (B)

研究機関：Tohoku University

2014年4月1日～ 2017年3月31日

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研究期間中に出血性椎骨動脈解離は計15例来院した．全例に脳血管撮影を行い，解離部の解剖学的特徴を検討し，解離周囲からの穿通枝の起始を確認した．血管撮影のデータを基に，computational fluid dynamicsの解析を行い，流体工学的に血流阻害効果の得られる条件を検討し，停滞する流れ環境下においても血流停止が生じず，分枝細血管の開存が維持される条件を検討した．シミュレーションでは新規ステントデザインを作成可能であったが，患者毎の解離部の形状バリエーションが多いこと，穿通枝を血管撮影で視認不可能な場合も多いこと，などから実際に臨床応用可能な新規ステントを開発するには至らなかった．
神経外傷急性期における局所低温療法の開発

冨永悌二, 遠藤俊毅, 齋藤竜太, 中川敦寛, 新妻邦泰, 杉山慎一郎, 船本健一

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

研究種目：Grant-in-Aid for Challenging Exploratory Research

研究機関：Tohoku University

2014年4月1日～ 2016年3月31日

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本研究の目的は、外傷性脳損傷に対する脳局所低温療法の開発であった。Convection-enhanced delivery法（CED法）を用いて、損傷局所に低温灌流液を注入し、脳保護効果を得ようと企図した。まず、正常ラットにおいて、冷却灌流中のMRモニタリング方法を確立した。次に、ラット外傷性脳損傷モデルを用いた概念実証を試みたが、疾患モデルにおいては脳圧亢進が速やかに起こり、冷却液灌流が困難であった。このような問題点に対して高浸透圧液注入の有用性が報告されていたが、本研究の実験系においては、その有用性を再現できなかった。灌流液を変更することでブレイクスルーを起こすべく、研究を継続している。
数値流体解析に基づく脳動脈瘤壁性状診断、破裂リスク予知と、治療への応用

新妻邦泰, 杉山慎一郎, 中川敦寛, 早瀬敏幸, 太田信, 船本健一, 荒船龍彦, 鷲尾俊克

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)

研究種目：Grant-in-Aid for Young Scientists (A)

研究機関：Tohoku University

2013年4月1日～ 2016年3月31日

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本研究の目的は、数値流体力学的解析結果を含む大規模脳動脈瘤データベースを構築し、これにデータマイニング手法を適用し、動脈瘤壁の性状や破裂リスクを算定することである。3年間の研究でデータベース登録を進め、当初予定していたものよりも多い500例規模のものが完成した。本データベースを用いて、動脈瘤の黄色調で固い壁の部位を数値流体力学から予測しうることを報告した。また、特定の脳底動脈瘤を対象に、破裂と血行動態の関連（論文投稿中）や、コイル塞栓術後の再発と血行動態の関連（論文投稿中）などの知見も得られた。データマイニング手法を適用した解析と動脈瘤の血行評価を行う外来システムは解析中・構築検討中である。

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社会貢献活動 9

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日本脳神経外科学会第77回総会市民公開講座　仙台市

2018年10月11日～ 2018年10月11日

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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」）
脳卒中と脳出血の話題「脳卒中の話」

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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」）

︎全件表示 ︎最初の5件までを表示