Elucidation of Early White Matter Lesions in Repetitive Mild Traumatic Brain Injury

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09022
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Ehime University
• Principal Investigator: Zhu Pengxiang 愛媛大学, 医学系研究科, 助教 (40380216)
• Co-Investigator(Kenkyū-buntansha): 阪中 雅広 愛媛大学, 医学部, 研究員 (60170601)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 軽度外傷性脳損傷 / インフラマソーム / 白質損傷 / 慢性外傷性脳症

Outline of Final Research Achievements

We showed that inflammasome mediated glia cell activation after repetitive mild traumatic brain injury (rmTBI) caused chronic damage of white matter, increased the risk of developing neurodegenerative diseases. Both in vivo and in vitro experiments confirmed that activated glial cells inhibited the maintenance and differentiation of oligodendrocyte precursor cells (OPCs). However, this inhibitory effect on OPCs was not observed in inflammasome-inactivated ASCKO glial cells. At 24 weeks post-rmTBI, the incidence of chronic traumatic encephalopathy (CTE) was significantly reduced in ASCKO mice compared to WT mice. These results suggest that suppressing neuroinflammation mediated by the inflammasome in the early stages following rmTBI can promote the recovery of white matter damage, improve higher-order brain dysfunction, and reduce the risk of developing CTE.

Free Research Field

軽度外傷性脳損傷

Academic Significance and Societal Importance of the Research Achievements

反複性軽度外傷性脳損傷（rmTBI）による高次脳機能障害と続発する慢性外傷性脳症（CTE）が大きな社会問題となっているが、その経過は未だに不明である。我々の研究では、rmTBI後インフラマソームを介して活性化したグリア細胞が損傷した白質の回復を遅らせて、高次脳機能障害を引き起こし、さらに神経変性疾患へのリスクを高めることを確認した。我々の研究結果は、今後rmTBIに対して新たな治療法開発につながると期待される。