beta1 integrin-pMLC endothelial permeability regulatory signaling as a novel therapeutic approach for neurological diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17018
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Keio University
• Principal Investigator: IZAWA Yoshikane 慶應義塾大学, 医学部(信濃町), 講師 (90468471)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 血管透過性 / 血液脳関門 / タイトジャンクション / β1インテグリン / neurovascular unit / 脳血管障害

Outline of Final Research Achievements

The temporal changes in fluorescence intensity of RITC or TRITC were analyzed semi-quantitatively. In both the cerebral ischemia model and the subcortical injection model using thrombin/β1 integrin inhibitory antibody, there was no significant increase in vascular permeability compared to the control group. This may be due to the variation in the size of the infarct foci among individual mice, and the occurrence of epileptic seizure-like symptoms after stereotaxic injection of thrombin/β1 integrin inhibitory antibody or saline, resulting in the large variation in the level of extravascular leakage among mice. For future evaluation, we are considering increasing the number of samples and modifying the experimental method.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

脳梗塞、脳出血、脳血管性認知症、そのほか様々な神経疾患では、脳血管の構造の脆弱化をきっかけとして、脳神経組織の機能障害が進むことが知られている。しかし、脳血管の脆弱化を示す一つの指標である「血管透過性亢進」のメカニズムは十分に解明されていない。当研究によりマウスの脳の血管透過性の変化を、生存した状態で連続的に観察する手法が確立された。今後、神経疾患の治療法開発の動物モデルとして応用が期待される。