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Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair

Acta Pharmacologica Sinica volume 47, pages 273–289 (2026)Cite this article

Abstract

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.

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Fig. 1: Schematic representation of neuroinflammation and immune-mediated neural damage from different cell sources after IS.
Fig. 2: Schematic representation of neuroinflammation and immune-mediated neural repair from different cell sources after IS.
Fig. 3: Signaling pathways regulating IS repair.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2022YFC3602805), the Scientific Research Common Program of Beijing Municipal Commission of Education (KM202310025027), and Beijing Natural Science Foundation (7252192). This work was also supported by the National Natural Science Foundation of China (81671149, 81870973).

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  1. These authors contributed equally: Hui Guo, Wen-cao Liu, Yan-yun Sun

Authors and Affiliations

  1. 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

    Hui Guo, Xin-chun Jin & Pan-pan Geng

  2. Shanxi Provincial People’s Hospital, Taiyuan, 030012, China

    Wen-cao Liu

  3. Institute of Neuroscience, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Yan-yun Sun

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  1. Hui Guo
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Guo, H., Liu, Wc., Sun, Yy. et al. Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair. Acta Pharmacol Sin 47, 273–289 (2026). https://doi.org/10.1038/s41401-025-01640-5

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