T cell receptor activation contributes to brain damage after intracerebral hemorrhage in mice

作者：Yuwen Xiu, Yingjie Wang, Ningning Wang, Ning Liu, Yinghua Jiang, Mengxuan Shi, Di Zhou, Thin Yadanar Sein, Mitchell D. Kilgore, Prasad V. G. Katakam, Qiang Liu, Wei-Na Jin, Fu‐Dong Shi, Xiaoying Wang, Aaron S. Dumont · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03402-w · 被引用次数：9 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Neuroinflammation and Neurodegeneration Mechanisms、Intracranial Aneurysms: Treatment and Complications

BACKGROUND: Our previous studies demonstrated that activated T cells accumulate in perihematomal regions following intracerebral hemorrhage (ICH) and exacerbate hemorrhagic brain injury. In the present study, we aimed to explore the mechanisms underlying brain-infiltrating T cell activation and the associated pathophysiological effects in neurological outcomes following ICH. METHODS: We employed standardized collagenase injection-induced and autologous blood injection models of ICH in male C57BL/6J mice. T cell receptor (TCR) activation, immune cell infiltration, and cytokine production were quantified through immunostaining, flow cytometry, and cytokine arrays at 1- and 3-days post-ICH. Brain edema volume was measured at 3 days post-ICH and neurobehavioral assessments were conducted up to 14 days post-ICH. Pharmacological inhibition of TCR activation was achieved using the TCR-specific inhibitor AX-024, administered intraperitoneally at a dosage of 10 mg/kg 1-hour post-ICH. RESULTS: Flow cytometry and immunostaining detected TCR activation of brain-infiltrating T cells. Specific TCR activation inhibitor AX-024 administration markedly reduced TCR activation and the production of pro-inflammatory cytokines in the brain at 1- and 3-days post-ICH. Moreover, AX-024 administration led to a significant reduction in the infiltration of other leukocyte populations, and significantly reduced brain edema while improved long-term sensorimotor and cognitive outcomes up to 14 days post-IC...