Guo Hui, Liu Wen-Cao, Sun Yan-Yun, Jin Xin-Chun, Geng Pan-Pan
Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100069, China.
Shanxi Provincial People's Hospital, Taiyuan, 030012, China.
Acta Pharmacol Sin. 2025 Aug 12. doi: 10.1038/s41401-025-01640-5.
Neuroinflammation and immune responses mediated by glial cells and immune cells play dual roles in the neural injury and repair of ischemic stroke (IS): glial cells and immune cells primarily have a detrimental role in the acute phase of IS, while they mainly serve a reparative function in the chronic phase. Thus, suppressing neuroinflammation and immune responses driven by glial and immune cells represents a major strategy in the treatment of IS. In this review, we provide an overview of the molecular mechanisms of neuroinflammation and immune responses mediated by glial cells and immune cells at different stages after IS and highlight the roles of different glial cells and immune cells in post-IS neural injury and repair. We also summarize the relevant molecular targets and clinical application challenges for reducing neuroinflammation and immune responses to promote IS repair. Current evidence supports that PD-1/PD-L1, DAPK1, HDAC3-p65-cGAS-STING could be the targets. In addition, we discuss some treatment strategies for reducing neuroinflammation and immune responses such as traditional Chinese medicine (TCM) and natural product therapy, stem cell-based therapy and biomaterials, as well as current clinical trial progress and prospects.
由胶质细胞和免疫细胞介导的神经炎症和免疫反应在缺血性中风(IS)的神经损伤和修复中发挥双重作用:胶质细胞和免疫细胞在IS急性期主要起有害作用,而在慢性期主要发挥修复功能。因此,抑制由胶质细胞和免疫细胞驱动的神经炎症和免疫反应是IS治疗的主要策略。在本综述中,我们概述了IS后不同阶段由胶质细胞和免疫细胞介导的神经炎症和免疫反应的分子机制,并强调了不同胶质细胞和免疫细胞在IS后神经损伤和修复中的作用。我们还总结了用于减轻神经炎症和免疫反应以促进IS修复的相关分子靶点和临床应用挑战。目前的证据支持PD-1/PD-L1、DAPK1、HDAC3-p65-cGAS-STING可能是靶点。此外,我们讨论了一些减轻神经炎症和免疫反应的治疗策略,如中药(TCM)和天然产物疗法、基于干细胞的疗法和生物材料,以及当前的临床试验进展和前景。