Investigation of the mechanism of increased vascular endothelial permeability in a mouse model of cerebral ischemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16585
• 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: Tsukada Naoki 慶應義塾大学, 医学部(信濃町), 研究員 (80868563)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脳血管透過性 / in vivo / 二光子顕微鏡 / マウスモデル / 脳虚血

Outline of Final Research Achievements

The purpose of this study is to establish an experimental system that can evaluate vascular permeability in vivo and to elucidate the mechanism and pathology of increased vascular permeability. In order to achieve the above goal, Tie2-GFP mice, in which vascular endothelial cells were fluorescently labeled, were stimulated to increase cerebral vascular permeability, and the head window was created and observed using a two-photon microscope. Vascular permeability enhancement was evaluated by quantifying the diffusion of rhodamine dextran outside of blood vessels (neuroparenchymal) from the fluorescence intensity. Fifteen cases were observed in each of the stereotaxic thrombin subcortical injection and sham-operated groups, and significant differences were observed in the fluorescence intensity of rhodamine dextran in the neuroparenchymal substance.

Free Research Field

脳卒中

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、血管透過性亢進メカニズム・病態の解明に取り組み、最終的に血管透過
性制御による脳血管障害、あるいは神経疾患に対する新たな治療法を確立することである。
本研究により、二光子顕微鏡下でのin vivo・リアルタイム・反復評価可能な脳血管内皮透過性評価モデルを確立した。in vivo で脳血管透過性に着目した脳虚血モデルは存在せず、この確立は血管内皮細胞の透過性亢進が関与する多くの病態・疾患に応用が可能であり、幅広い研究分野への波及が期待される。