Role of galectin-3 for the mechanism of early brain injury after subarachnoid hemorrhage.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16640
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Mie University
• Principal Investigator: Shiba Masato 三重大学, 医学部附属病院, 講師 (30595682)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ガレクチン-3 / くも膜下出血 / 早期脳損傷

Outline of Final Research Achievements

The aim of this study was to evaluate whether modified citrus pectin (MCP; galectin-3 inhibitor) prevents post-SAH early brain injury, focusing on blood-brain barrier (BBB) disruption. Male adult mice underwent sham or filament perforation SAH modeling, followed by an intracerebroventricular injection of vehicle or drug. First, vehicle-treated and MCP-treated mice were assessed by neuroscore, brain water content, Evans blue extravasation, Western blotting, immunostaining. Then, vehicle or R-galectin-3 (recombinant galectin-3) was administered to SAH mice simultaneously with vehicle or MCP, and neuroscore, Evans blue extravasation and IgG immunostaining were evaluated. MCP prevented post-SAH BBB disruption by inhibiting galectin-3, of which the mechanisms may include binding to TLR4 and activating ERK1/2, STAT-3, and MMP-9. R-galectin-3 blocked the neuroprotective effects of MCP. This study suggested galectin-3 would be a novel therapeutic target against early brain injury after SAH.

Free Research Field

くも膜下出血

Academic Significance and Societal Importance of the Research Achievements

くも膜下出血は予後不良な疾患であり、その治療介入可能な予後不良因子として早期脳損傷が挙げられる。しかしその病態の詳細なメカニズムについては未だ明らかとなっておらず、したがって、特異的な治療法も無いのが現状である。ガレクチン-3は種々の組織の細胞内外に存在し、アポトーシスや炎症における信号伝達に関与するとされている。今回ガレクチン-3がSAH後の脳において発現が増加し、様々な細胞内情報伝達機構を通して血液脳関門障害と脳浮腫に関連していることが明らかとなった。本研究の成果は将来ガレクチン-3抑制を介する新たな早期脳損傷に対する治療法の開発へと発展する可能性があると考えられる。