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Protective role of sphingo-lipid against brain ischemic re-perfusion injury

Research Project

Project/Area Number 16K19992
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionHokkaido University

Principal Investigator

Kawabori Masahito  北海道大学, 大学病院, 特任講師 (50399870)

Research Collaborator Wang Zifeng  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脳梗塞 / フィンゴリモド / 炎症反応 / 炎症 / 脳血液関門 / FTY720 / Sphingolipid / ラット / 虚血再灌流 / 脳・神経
Outline of Final Research Achievements

Treatment against acute ischemic stroke has shown great advancement with thrombectomy. However, severe brain edema and subsequent brain damage may occur even after the rapid recanalization. Ischemic/reperfusion (I/R) injury is considered one of the major causes of the damage and recently draws increasing attention for novel therapeutic target. FTY720 (fingolimod), a widely known sphingosine-1-phosphate (S1P) receptor agonist approved as a treatment for multiple sclerosis due to its strong anti-inflammatory effect plays a variety of roles in neuroprotection including reduction of neuroinflammation. However, the role of FTY720 against I/R injury has not been fully elucidated. FTY720 significantly reduced infarction size and numbers of cell with apoptosis, and improved neurological score after I/R injury compared with the vehicle group. FTY720 significantly inhibits worsening of inflammation 9 days after insult. The present results suggest that FTY720 can ameliorates I/R injury

Academic Significance and Societal Importance of the Research Achievements

脳梗塞に対する新たな治療法である再開通療法は多くの患者を救うことが出来る様になった。しかし新たな問題として再開通後に血流が急速に戻ることで傷ついた細胞がダメージを受ける虚血再灌流障害がクローズアップされている。本研究はその虚血再灌流障害を軽減できる方法の発見で有り、その機序まで深く踏み込んでいる。特に新規的な発見として脳梗塞再灌流時に生じる炎症をFTY720が急性期では無く亜急性期にブロックすること、また脳血液関門の崩壊を防ぐ効果があることを示すことが出来た。これは将来の新薬開発等に繋がる研究である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] FTY720 (fingolimod) ameliorates brain injury through multiple mechanisms and is a strong candidate for stroke treatment2019

    • Author(s)
      Zifeng Wang, Masahito Kawabori, Kiyohiro Houkin
    • Journal Title

      Current Medicinal Chemistry

      Volume: 印刷中

    • NAID

      120006869886

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 中国における中枢神経疾患に対する細胞治療の最新動向2018

    • Author(s)
      王シホウ, 譚成博, 川堀真人, 七戸秀夫, 寶金清博.
    • Journal Title

      北海道医学雑誌

      Volume: Epub ahead of print

    • NAID

      120006482592

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] FTY720 (fingolimod) ameliorates brain injury through multiple mechanisms and is a strong candidate for stroke treatment2019

    • Author(s)
      Zifeng Wang, Masahito Kawabori, Kiyohiro Houkin
    • Organizer
      International Stroke Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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