Breakthrough of the effect and mechanism of Rho kinase inhibitor fasudil on blood-brain barrier

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09531
• 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: Nagasaki University
• Principal Investigator: Matsunaga Yuki 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (80772136)
• Co-Investigator(Kenkyū-buntansha): 中川 慎介 福岡大学, 薬学部, 准教授 (10404211) ; 諸藤 陽一 長崎大学, 病院(医学系), 講師 (40437869)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 血液脳関門 / Rho kinase阻害薬 / 脳卒中 / ペリサイト / アストロサイト

Outline of Final Research Achievements

This study demonstrated the protective effect of the Rho kinase inhibitor fasudil on the BBB. Fasudil maintained the tight junction structure and improved the function of the BBB by enhancing the expression of tight junction proteins. Fasudil was also found to protect the BBB from damage induced by oxygen-glucose deprivation and reoxygenation. This protective effect was confirmed in both monoculture model and co-culture model. It was suggested that it has a BBB-protective effect through two pathways that act indirectly on pericytes and astrocytes, and directly on endothelial cells.

Free Research Field

血液脳関門

Academic Significance and Societal Importance of the Research Achievements

Rho kinase阻害薬であるfasudilは急性期脳梗塞治療で最も重要な虚血後8 時間以内をピークとしてBBB機能を改善した。またこのBBB保護効果は既に実臨床で用いられている血中濃度レベルで濃度依存的に認められた。したがって、fasudilは急性期脳梗塞に対するBBB保護剤として有用であり、かつ安全に使用することが可能であると考えられる。