Ly6C-high monocytes alleviate brain injury in experimental subarachnoid hemorrhage in mice

作者：Huaijun Chen, Chaoran Xu, Hanhai Zeng, Zhihua Zhang, Ning Wang, Yinghan Guo, Yonghe Zheng, Siqi Xia, Hang Zhou, Xiaobo Yu, Xiongjie Fu, Tianchi Tang, Xinyan Wu, Zihang Chen, Yucong Peng, Jing Cai, Jianru Li, Feng Yan, Chi Gu, Gao Chen, Jingyin Chen · 发表于：Journal of Neuroinflammation · 年份：2023 · DOI：10.1186/s12974-023-02939-y · 被引用次数：29 · 研究领域：Intracranial Aneurysms: Treatment and Complications、Neuroinflammation and Neurodegeneration Mechanisms、Intracerebral and Subarachnoid Hemorrhage Research

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. METHODS: A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. RESULTS: The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregul...