Endothelial Changes at Different Stages After Ischemic Stroke Contribute to the Regulation of Immune Cell Infiltration

作者：Xuejiao Dai, Xiaotao Zhang, Jiarui Chen, Zhang Qia, Huaming Li, An Ping, Yuchen Liu, Jingyi Zhou, Jianmin Zhang, Ligen Shi, Jianan Lü · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70456 · 被引用次数：9 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Single-cell and spatial transcriptomics、Barrier Structure and Function Studies

AIMS: Following ischemic stroke, peripheral immune cell infiltration is characterized by myeloid cell predominance in the acute phase and lymphoid cell infiltration in the subacute to chronic phases. Endothelial cells, as a critical interface between the peripheral circulation and the brain, upregulate adhesion molecules to facilitate immune cell infiltration. However, it remains unclear whether endothelial cells exhibit functional differences at different stages after ischemic stroke and how these differences affect immune cell infiltration. METHODS: We performed single-cell RNA sequencing on peripheral immune and endothelial cells from Sham and middle cerebral artery occlusion (MCAO) mice at 3 and 14 days post-MCAO. Subsequent analysis of the sequencing data, combined with flow cytometry and immunofluorescence staining, was used to investigate the relationship between endothelial cell changes at different stages of stroke and immune cell infiltration. RESULTS: We observed that the infiltration capacity of peripheral immune cells did not significantly increase at different stages after MCAO. However, endothelial cells underwent significant changes. By Day 3 post-MCAO, there was an increased proportion of venous endothelial cells with enhanced angiogenesis and adhesion functions. In this acute phase, newly formed venous endothelial cells with high expression of the adhesion molecule ICAM-1 were observed, promoting the infiltration of myeloid cells and NKT cells. From the acut...