Development of endogenous functional recovery therapy after ischemic stroke targeting extracellular matrix protein

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20693
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Shibahara Tomoya 九州大学, 医学研究院, 共同研究員 (20908496)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 脳梗塞 / 内因性機能回復 / fibronectin / ペリサイト / マクロファージ / laminin α2 / アストロサイト / オリゴデンドロサイト前駆細胞

Outline of Final Research Achievements

The purpose of this research project is to investigate the mechanism of functional recovery mediated by an extracellular matrix (ECM) remodeling after stroke, which controls intercellular interaction. Within the infarct area, pericytes produced fibronectin and promoted macrophage-mediated clearance of necrotic tissue. Furthermore, pericytes within the infarct area regulated the production of astrocytic laminin α2 in peri-infarct areas, which led to the differentiation and remyelination of oligodendrocyte progenitor cells (OPCs), resulting in functional recovery through a reorganization of neural network. We conclude that reciprocal interactions among pericytes, macrophages, astrocytes, and OPCs and the ECM proteins-mediated microenvironment that facilitates these cell-cell interactions are important for endogenous functional recovery.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞によって運動機能障害が生じると、寝たきりの状態となり介護が必要な状況に陥る。脳梗塞急性期以降の機能回復を促進させる治療はリハビリテーションのみであり、機能回復をもたらす治療の開発は喫緊の課題である。脳梗塞発症後は、脳組織の神経系細胞や血管系細胞、傷害後に局所動員される血球系細胞が相互に作用して内因性機能回復機構が働く。本研究課題では脳梗塞後に再構築された細胞外マトリックス蛋白が、細胞間相互作用に重要な役割を果たし、内因性機能回復を誘導する機序の一端を担うことを明らかにした。今後細胞外マトリックスをターゲットとした新規治療法開発の基盤となることが期待される。