Collateral circulation as a therapeutic target of ischemic stroke

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Kitagawa Kazuo 東京女子医科大学, 医学部, 教授 (70301257)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遠隔虚血コンディショニング / 脳梗塞

Outline of Final Research Achievements

We hypothesized that remote ischemic conditining (RIC) enhances collateral circulation through endothelial activation and mitigates ischemic injury. Methods: We tested RIC and sham procedure 30 min after middle cerebral artery occlusion (MCAO) in mice. Immediately after RIC, early lesions on MRIDWI and pial collateral vessels were examined. The infarct volume was examined until 48 h after daily RIC. We assessed the phosphorylation level of eNOS and p-Akt in the ischemic hemisphere. Finally, the effects of NOS inhibitors were examined in mice treated with RIC after MCAO. Results: RIC diminished early ischemic lesions and enlarged pial collaterals after MCAO. RIC also mitigated infarct volume up to 48 h after MCAO. RIC upregulated the phosphorylation of eNOS and Akt. eNOS inhibitors abolished the beneficial effect of RIC. Conclusions: RIC could enhance pial collateral circulation and diminish infarct volume. Activation of endothelial function could underlie the beneficial effects of RIC.

Free Research Field

脳神経内科

Academic Significance and Societal Importance of the Research Achievements

動物虚血モデルでの遠隔虚血コンディショニングの有効性がマウス中大脳動脈永久閉塞モデルで示され、さらにその機序として脳軟膜動脈吻合発達による虚血重症度の軽減が主であることが示された。ヒト脳梗塞症例において遠隔虚血コンディショニングを応用する際にその機序を踏まえプロトコールを組むことが重要と考えられ、本研究成果はヒト脳梗塞を対象とした臨床試験を実施するに際いて有益な情報を与えると考えられる。