Development of a novel method to protect cerebrovascular based on the regulation of lysophospholipid

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Nagasaki University
• Principal Investigator: NAKAGAWA Shinsuke 長崎大学, 医歯薬学総合研究科(医学系), 講師 (10404211)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血液脳関門 / S1P / 虚血再灌流

Outline of Final Research Achievements

Lysophospholipids, which are physiologically active lipids, play important roles in immunity and the vascular system. In this study, we investigated the role of lysophospholipids, such as sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), at the blood-brain barrier (BBB). Examination using the in vitro BBB model and the in vivo model revealed that S1P and LPA have an effect on regulating BBB function. Furthermore, we have found that inhibition of S1P signaling by sphingosine kinase inhibitor (SKI-II) or ABCA1 transporter inhibitor (Probucol) prevents BBB dysfunction after ischemia both in vitro and in vivo.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

生理活性脂質であるリゾリン脂質（スフィンゴシン1-リン酸（S1P）やリゾホスファチジン酸（LPA）など）は、多くの病態との関連が指摘されていたが、脳血管障害においてどのような役割を担っているのかは、不明な点が残されていた。本研究により、S1PやLPAによる脳血管機能調節機構が明らかとなり、新たな脳血管保護方法の開発へとつながる基礎データを示すことに成功した。