Role of epidermal growth factor receptor in early brain injury after subarachnoid hemorrhage

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16605
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Mie University
• Principal Investigator: Nakano Fumi 三重大学, 医学部附属病院, 診療等従事者 (50850731)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: くも膜下出血 / 早期脳損傷

Outline of Final Research Achievements

Subarachnoid hemorrhage (SAH) is a devastating disease which affecting relatively young people. Cerebral vasospasm and early brain injury (EBI) have been suggested to contribute to delayed cerebral ischemia (DCI) after SAH. EBI, such as neuronal apoptosis, has not been fully investigated. In this study, we investigated whether epidermal growth factor receptor (EGFR) activation results in neuronal apoptosis and sought signaling pathways under EGFR activation in a mouse SAH model.
SAH mouse showed deteriorated neurological function, brain edema, increased neuronal apoptosis, and these observations were improved in SAH-EGFR inhibitor group. Western blot and immunohistochemistry revealed that expressions of phosphorylated (p-) EGFR, nuclear factor-kappa B (NFkB) inducing kinase (NIK) in the nucleus, NFkB were increased in neurons of the SAH group, and decreased in the SAH-EGFR inhibitor group. EGFR/NIK/NFkB is suggested to be involved in neuronal apoptosis after SAH in mice.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

SAH患者の30-40%でDCIが生じ、これが脳梗塞へと発展すると転帰不良の原因となる。
本研究結果は、DCIへ至る原因の一つである神経細胞アポトーシスに関して、EGFRの活性化及びその下流にnuclear factor (NF)-kappa B inducing kinase (NIK)/NF-kappaB経路が働くことを示している。これにより、将来的にはEGFRを分子標的とした新しいEBI治療法の開発、そして予後の改善へと発展していくことが期待される。