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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19992
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Hokkaido 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
• Keywords: 脳梗塞 / フィンゴリモド / 炎症反応

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

Free Research Field

脳神経外科学

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。