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Development of novel treatment and prognostic prediction for acute brain injury after aneurysmal subarachnoid hemorrhage.

Research Project

Project/Area Number 18K16566
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionYokohama City University

Principal Investigator

Takase Hajime  横浜市立大学, 医学研究科, 客員研究員 (00549975)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsくも膜下出血 / 急性期脳損傷 / 分子メカニズム / 血管内皮 / 神経炎症 / ミクログリア / cell-cell interaction / translational study / 接着結合
Outline of Final Research Achievements

We investigated the role of soluble vascular-endothelial (sVE) cadherin in aneurysmal subarachnoid hemorrhage (aSAH) that the inflammatory mechanism is strongly associated with the pathophysiology. The clinical part of our reverse-translational study demonstrated that CSF level of sVE-cadherin was negatively correlated with clinical outcome of aSAH patients. Additionally, the experimental part showed that sVE-cadherin activated an inflammatory cascade in microglia. These findings support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

Academic Significance and Societal Importance of the Research Achievements

本研究において、くも膜下出血における血管内皮細胞由来分子ーミクログリアの新たなcell-cell interactionと、新たな神経炎症分子メカニズムの存在が示唆された。血管内皮の代謝分子VE-cadherinが、血液脳関門の恒常性維持という本来の役割にとどまらず、中枢神経系の炎症において新たな生物学的な機能を有することを示した点で、学術的意義も大きいと考えられる。これらの知見を他の中枢神経疾患に応用することで、新たな研究展開が可能であり、将来の治療開発を通して世界の社会福祉に大きく貢献できる可能性がある。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 14 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 6 results)

  • [Int'l Joint Research] Massachusetts General Hospital/Harvard Medical School/Brigham and Women's Hospital(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] マサチューセッツ総合病院・ハーバード大学/ピッツバーグ大学メディカルセンター(米国)

    • Related Report
      2018 Research-status Report
  • [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

    • Related Report
      2019 Annual Research Report
    • 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

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Axonal regeneration and functional recovery driven by endogeneous Nogo receptor antagonist LOTUS in a rat model of unilateral pyramidotomy.2020

    • Author(s)
      Ueno, R., Takase, H., Suenaga, J., Kishimoto, M., Kurihara, Y., Takei, K., Kawahara, N., and Yamamoto
    • Journal Title

      Experimental Neurology

      Volume: 323 Pages: 113068-113068

    • DOI

      10.1016/j.expneurol.2019.113068

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / 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

    • Related Report
      2019 Annual Research Report
    • 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

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion.2020

    • Author(s)
      Ohtomo R, Kinoshita K, Ohtomo G, Takase H, Hamanaka G, Washida K, Islam MR, Wrann CD, Katsuki H, Iwata A, Lok J, Lo EH, Arai K.
    • Journal Title

      Transl Stroke Res.

      Volume: - Issue: 3 Pages: 496-502

    • DOI

      10.1007/s12975-019-00734-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in Cerebral Ischemia/Reperfusion Injury2019

    • Author(s)
      Kishimoto M, Suenaga J, Takase H, Araki K, Yao T, Fujimura T, Murayama K, Okumura K, Ueno R, Shimizu N, Kawahara N, Yamamoto T, Seko Y.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 13512-13512

    • DOI

      10.1038/s41598-019-50073-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 進行性の認知機能低下を来している高齢者の脳出血2019

    • Author(s)
      大友亮、高瀬創
    • Journal Title

      内科

      Volume: 4 Pages: 843-844

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Delayed C5 Palsy After Anterior Cervical Decompression Surgery: Preoperative Foraminal Stenosis and Postoperative Spinal Cord Shift Increase the Risk of Palsy2018

    • Author(s)
      Takase H, Murata H, Sato M, Tanaka T, Miyazaki R, Yoshizumi T, Tateishi K, Kawahara N, Yamamoto T
    • Journal Title

      World Neurosurgery

      Volume: 50(18) Pages: 8732049-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective effects of a radical scavenger edaravone on oligodendrocyte precursor cells against oxidative stress.2018

    • Author(s)
      Takase H, Liang AC, Miyamoto N, Hamanaka G, Ohtomo R, Maki T, Pham LD, Lok J, Lo EH, Arai K.
    • Journal Title

      Neurosci Letters

      Volume: 6;668 Pages: 120-125

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A radical scavenger edaravone and oligodendrocyte protection/regeneration.2018

    • Author(s)
      Takase H, Lok J, Arai K.
    • Journal Title

      Neural Regen Res.

      Volume: 13(9) Pages: 1550-1551

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] White-matter repair: Interaction between oligodendrocytes and the neurovascular unit2018

    • Author(s)
      Hamanaka G, Ohtomo R, Takase H, Lok J, Arai K
    • Journal Title

      Brain Circulation

      Volume: 4 (3) Pages: 118-123

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of oligodendrocyte-neurovascular unit in white matter repair.2018

    • Author(s)
      Hamanaka G, Ohtomo R, Takase H, Lok J, Arai K.
    • Journal Title

      Neurosci Lett.

      Volume: 25;684 Pages: 175-180

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Three-dimensional multimodality fusion imaging as an educational and planning tool for deep-seated meningiomas.2018

    • Author(s)
      Sato M, Tateishi K, Murata H, Kin T, Suenaga J, Takase H, Yoneyama T, Nishii T, Tateishi U, Yamamoto T, Saito N, Inoue T, Kawahara N.
    • Journal Title

      Br J Neurosurg.

      Volume: 26 Pages: 1-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 「ボストン日本人脳外科医の会」便り2018

    • Author(s)
      伊藤博崇、北村洋平、清川樹里、五味正憲、杉本至健、高瀬創、 千田光平、長嶋宏明、原岡怜、柳澤毅、 Emiri T. Mandeville、脇本浩明
    • Journal Title

      脳神経外科速報

      Volume: 8 Pages: 818-822

    • Related Report
      2018 Research-status Report
  • [Presentation] White matter damage and microglial alterations after concussive brain injury.2019

    • Author(s)
      Takase H, Ohtomo R, Wang X, Lo EH, Chung JY, Whalen MJ, Arai K, Lok J
    • Organizer
      BRAIN 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Treadmill exercise suppresses cognitive decline and increases white matter oligodendrocyte precursor cells in a mouse model of prolonged cerebral hypoperfusion2019

    • Author(s)
      Ohtomo R, Ohtomo G, Takase H, Hamanaka G, Iwata A, Lok J, Lo EH, Arai K
    • Organizer
      BRAIN 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biphasic roles of pentraxin 3 in cerebrovascular responses after white matter stroke2019

    • Author(s)
      Shindo A, Ohtomo R, Takase H, Hamanaka G, Maki T, Egawa N, Lok J, Tomimoto H, Lo EH, Arai K
    • Organizer
      BRAIN 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microglial responses after phagocytosis: e. coli bioparticles, but not cell debris or amyloid beta, induce matrix metalloproteinase-9 secretion in vitro2019

    • Author(s)
      Hamanaka G, Ohtomo R, Takase H, Lok J, Lo EH, Arai K
    • Organizer
      BRAIN 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oligodendrocyte injury in concussive brain injury2018

    • Author(s)
      Takase H, Chung JY, Wu L, Wang X, Lo EH, Whalen MJ, Arai K, Lok J
    • Organizer
      Neurotrauma 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Soluble VE-cadherin is elevated in CSF in Subarachnoid Hemorrhage2018

    • Author(s)
      Takase H, Chou SH, Arai K, Lo EH, Lok J
    • Organizer
      10th Annual MGHfC Research Day
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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