Role of neuroinflammation in the molecular mechanism of cognitive dysfunction after subarachnoid hemorrhage

• Project/Area Number: 20K09330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Yokohama City University
• Principal Investigator: TAKASE Hajime 横浜市立大学, 附属病院, 助教 (00549975)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: くも膜下出血 / 認知機能障害 / 分子メカニズム / 認知機能 / 神経炎症 / 白質障害

Outline of Research at the Start

動脈瘤性くも膜下出血(SAH)後の障害がもたらす損失は甚大で,世界的な問題であり続けている。なかでもSAH後の認知機能障害は, 約1/3ものSAH生存者に認めるなど, その病態解明と治療法開発は社会的な大命題である。一方でSAHの研究は近年,急性期の脳内微小環境障害 (SAH後急性期脳損傷)が特に重要視され, 焦点が大きくシフトしている。
本研究では, 新規に発見された「神経炎症のトリガーとなる細胞間メカニズム」に着目し, SAH後急性期における同メカニズムの関与をReverse-translational studyの手法を用いて詳細に分析して新規の治療法開発を目指す。

Outline of Final Research Achievements

The aim of this research project is to identify the molecular mechanism of cognitive dysfunction after subarachnoid hemorrhage.
At present, all data is under analysis and thus unpublished.

Academic Significance and Societal Importance of the Research Achievements

くも膜下出血後認知機能障害のメカニズムに関して、基礎研究的なアプローチで探求している。現在、これまで採取したサンプルやデータを解析中である。今後、認知機能関連部位における炎症性損傷機構が時間変化とともに明らかになる可能性があり、将来の治療応用にむけた学術的な基盤の一部となることが期待される。

Research Products

• [Journal Article] Antiplatelet Therapy: A Double-Edged Sword in Aneurysm Treatment? (2023)
  • Author(s): Takase Hajime、Salem Mohamed M.、Burkhardt Jan-Karl
  • Journal Title: World Neurosurgery Volume: NA Pages: 274-275
  • DOI: 10.1016/j.wneu.2023.02.125
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antiplatelet therapy for standalone coiling of ruptured intracranial aneurysms: a systematic review and meta-analysis (2022)
  • Author(s): Takase Hajime、Tatezuki Junya、Salem Mohamed M、Tayama Katsuko、Nakamura Yoshihiko、Burkhardt Jan-Karl、Yamamoto Tetsuya
  • Journal Title: Journal of NeuroInterventional Surgery Volume: NA Issue: 12 Pages: 1207-1212
  • DOI: 10.1136/neurintsurg-2021-018346
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of cerebral amyloid angiopathy on the brain vasculome (2022)
  • Author(s): Deng Wenjun、Guo Shuzhen、van Veluw Susanne J.、Yu Zhanyang、Chan Su Jing、Takase Hajime、Arai Ken、Ning MingMing、Greenberg Steven M.、Lo Eng H.、Bacskai Brian J.
  • Journal Title: Aging Cell Volume: 21 Issue: 8
  • DOI: 10.1111/acel.13503
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone Invasive Meningioma: Recent Advances and Therapeutic Perspectives (2022)
  • Author(s): Takase Hajime、Yamamoto Tetsuya
  • Journal Title: Frontiers in Oncology Volume: 12
  • DOI: 10.3389/fonc.2022.895374
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptome Profiling of Mouse Corpus Callosum After Cerebral Hypoperfusion (2021)
  • Author(s): Takase Hajime、Hamanaka Gen、Ohtomo Ryo、Ishikawa Hidehiro、Chung Kelly K.、Mandeville Emiri T.、Lok Josephine、Fornage Myriam、Herrup Karl、Tse Kai-Hei、Lo Eng H.、Arai Ken
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9
  • DOI: 10.3389/fcell.2021.685261
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Motor Tract Reorganization after Acute CNS Injury: A Translational Perspective (2021)
  • Author(s): Takase H*, Regenhardt RW.
  • Journal Title: Neural Regen Res Volume: 16(6) Issue: 6 Pages: 1144-1149
  • DOI: 10.4103/1673-5374.300330
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mature Adult Mice with Exercise-Preconditioning Show Better Recovery after Intracerebral Hemorrhage. (2021)
  • Author(s): Kinoshita K, Hamanaka G, Ohtomo R, Takase H, Chung KK, Lok J, Lo EH, Katsuki H, Arai K.
  • Journal Title: Stroke Volume: in press Issue: 5 Pages: 1861-1865
  • DOI: 10.1161/strokeaha.120.032201
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of A-kinase Anchor Protein 12 in Astrocyte and Oligodendrocyte Precursor Cell in Postnatal Corpus Callosum. (2021)
  • Author(s): Takase H, Hamanaka G, Ohtomo R, Park JH, Chung KK, Gelman IH, Kim KW, Lok J, Lo EH, Arai K.
  • Journal Title: Stem Cell Rev Rep Volume: in press Issue: 4 Pages: 1446-1455
  • DOI: 10.1007/s12015-021-10118-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Treadmill Exercise During Cerebral Hypoperfusion Has Only Limited Effects on Cognitive Function in Middle-Aged Subcortical Ischemic Vascular Dementia Mice. (2021)
  • Author(s): Ohtomo R, Ishikawa H, Kinoshita K, Chung KK, Hamanaka G, Ohtomo G, Takase H, Wrann CD, Katsuki H, Iwata A, Lok J, Lo EH, Arai K.
  • Journal Title: Front Aging Neurosci. Volume: 13 Pages: 756537-756537
  • DOI: 10.3389/fnagi.2021.756537
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ErbB3 is a critical regulator of cytoskeletal dynamics in brain microvascular endothelial cells: Implications for vascular remodeling and blood-brain-barrier modulation. (2021)
  • Author(s): Wu L, Islam MR, Lee J, Takase H, Guo S, Andrews AM, Buzhdygan TP, Mathew J, Li W, Arai K, Lo EH, Ramirez SH, Lok J
  • Journal Title: J Cereb Blood Flow Metab Volume: in press Issue: 9 Pages: 2242-2255
  • DOI: 10.1177/0271678x20984976
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pineal parenchymal tumor of intermediate differentiation: a systematic review and contemporary management of 389 cases reported during the last two decades (2021)
  • Author(s): Takase Hajime、Tanoshima Reo、Singla Navneet、Nakamura Yoshihiko、Yamamoto Tetsuya
  • Journal Title: Neurosurgical Review Volume: 45 Issue: 2 Pages: 1135-1155
  • DOI: 10.1007/s10143-021-01674-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Practical Arachnoid Anatomy for the Technical Consideration of Galen Complex Dissection: Cadaveric and Clinical Evaluation (2021)
  • Author(s): Miyake Shigeta、Suenaga Jun、Nakamura Taishi、Akimoto Taisuke、Suzuki Ryosuke、Ohtake Makoto、Takase Hajime、Tateishi Kensuke、Shimizu Nobuyuki、Murata Hidetoshi、Funakoshi Kengo、Sawamura Yutaka、Yamamoto Tetsuya
  • Journal Title: World Neurosurgery Volume: 151 Pages: 581-587
  • DOI: 10.1016/j.wneu.2021.04.041
  • Peer Reviewed / Open Access
• [Journal Article] Biphasic roles of pentraxin 3 in cerebrovascular function after white matter stroke. (2021)
  • Author(s): Shindo A, Takase H, Hamanaka G, Chung KK, Mandeville ET, Egawa N, Maki T, Borlongan M, Takahashi R, Lok J, Tomimoto H, Lo EH, Arai K
  • Journal Title: CNS Neurosci Ther Volume: 27(1) Issue: 1 Pages: 60-70
  • DOI: 10.1111/cns.13510
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage. (2020)
  • Author(s): Takase H, Chou SH, Hamanaka G, Ohtomo R, Islam MR, Lee JW, Hsu L, Mathew J, Reyes-Bricio E, Hayakawa K, Xing C, Ning MM, Wang X, Arai K, Lo EH, Lok J.
  • Journal Title: Neurology Volume: 94(12) Issue: 12
  • DOI: 10.1212/wnl.0000000000008868
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anterior Cervical Decompression and C5 Palsy: A Systematic Review and Meta-Analysis of Three Reconstructive Surgeries. (2020)
  • Author(s): Takase H*, Tayama K, Nakamura Y, Mathew J, Regenhardt RW, Murata H, Yamamoto T.
  • Journal Title: Spine (Phila Pa 1976) Volume: 45(22) Issue: 22 Pages: 1587-1597
  • DOI: 10.1097/brs.0000000000003637
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Translating concepts of neural repair after stroke: Structural and functional targets for recovery. (2020)
  • Author(s): Regenhardt RW, Takase H, Lo EH, Lin DJ.
  • Journal Title: Restorative Neurology and Neuroscience Volume: 38(1) Issue: 1 Pages: 67-92
  • DOI: 10.3233/rnn-190978
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Microglial responses after phagocytosis: Escherichia coli bioparticles, but not cell debris or amyloid beta, induce matrix metalloproteinase-9 secretion in cultured rat primary microglial cells. (2020)
  • Author(s): Hamanaka G, Kubo T, Ohtomo R, Takase H, Reyes-Bricio E, Oribe S, Osumi N, Lok J, Lo EH, Arai K.
  • Journal Title: Glia Volume: 68(7) Issue: 7 Pages: 1435-1444
  • DOI: 10.1002/glia.23791
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke. (2020)
  • Author(s): Seo JH, Maki T, Miyamoto N, Choi YK, Chung KK, Hamanaka G, Park JH, Mandeville ET, Takase H, Hayakawa K, Lok J, Gelman IH, Kim KW, Lo EH, Arai K.
  • Journal Title: Int J Mol Sci Volume: 21(23) Issue: 23 Pages: 9078-9078
  • DOI: 10.3390/ijms21239078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Different responses after intracerebral hemorrhage between young and early middle-aged mice (2020)
  • Author(s): Kinoshita K, Ohtomo R, Takase H, Hamanaka G, Chung KK, Lok J, Katsuki H, Arai K.
  • Journal Title: Neurosci Lett Volume: 735 Pages: 135249-135249
  • DOI: 10.1016/j.neulet.2020.135249
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Thiel's embalming method with additional intra-cerebral ventricular formalin injection (TEIF) for cadaver training of head and brain surgery. (2020)
  • Author(s): Miyake S, Suenaga J, Miyazaki R, Sasame J, Akimoto T, Tanaka T, Ohtake M, Takase H, Tateishi K, Shimizu N, Murata H, Funakoshi K, Yamamoto T.
  • Journal Title: Anatomical Science International Volume: N/A Issue: 4 Pages: 564-570
  • DOI: 10.1007/s12565-020-00545-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] くも膜下出血後の神経炎症：中枢神経系における可溶性VE-cadherinの新たな役割 (2021)
  • Author(s): Takase H, Chou SHY, Hamanaka G, Ohtomo R, Islam MR, Lee JW, Hsu L, Mathew J, Reyes-Bricio E, Hayakawa K, Xing C, Ning MM, Wang X, Arai K, Lo EH, Lok J
  • Organizer: 第50回日本脳卒中の外科学会学術集会
• [Book] Handbook of Experimental Pharmacology (2020)
  • Author(s): Li W, Cao F, Takase H, Arai K, Lo EH, Lok J.
  • Total Pages: 320
  • Publisher: Springer
  • ISBN: 9783319581927