Zhang Xiaotao, Li Huaming, Gu Yichen, Ping An, Chen Jiarui, Zhang Qia, Xu Zhouhan, Wang Junjie, Tang Shenjie, Wang Rui, Lu Jianan, Lu Lingxiao, Jin Chenghao, Jin Ziyang, Zhang Jianmin, Shi Ligen
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, China.
Nat Commun. 2025 Mar 31;16(1):3089. doi: 10.1038/s41467-025-58254-y.
Ischemic stroke recovery involves dynamic interactions between the central nervous system and infiltrating immune cells. Peripheral immune cells compete with resident microglia for spatial niches in the brain, but how modulating this balance affects recovery remains unclear. Here, we use PLX5622 to create spatial niches for peripheral immune cells, altering the competition between infiltrating immune cells and resident microglia in male mice following transient middle cerebral artery occlusion (tMCAO). We find that early-phase microglia attenuation promotes long-term functional recovery. This intervention amplifies a subset of monocyte-derived macrophages (RAMf) with reparative properties, characterized by high expression of GPNMB and CD63, enhanced lipid metabolism, and pro-angiogenic activity. Transplantation of RAMf into stroke-affected mice improves white matter integrity and vascular repair. We identify Mafb as the transcription factor regulating the reparative phenotype of RAMf. These findings highlight strategies to optimize immune cell dynamics for post-stroke rehabilitation.
缺血性中风恢复涉及中枢神经系统与浸润性免疫细胞之间的动态相互作用。外周免疫细胞与驻留小胶质细胞竞争大脑中的空间生态位，但调节这种平衡如何影响恢复仍不清楚。在这里，我们使用PLX5622为外周免疫细胞创造空间生态位，改变雄性小鼠短暂大脑中动脉闭塞（tMCAO）后浸润性免疫细胞与驻留小胶质细胞之间的竞争。我们发现早期小胶质细胞衰减促进长期功能恢复。这种干预放大了具有修复特性的单核细胞衍生巨噬细胞（RAMf）亚群，其特征是高表达GPNMB和CD63、增强的脂质代谢和促血管生成活性。将RAMf移植到中风小鼠体内可改善白质完整性和血管修复。我们确定Mafb为调节RAMf修复表型的转录因子。这些发现突出了优化免疫细胞动态以促进中风后康复的策略。
