Immune interventions in stroke: current progress and perspectives

Acute ischemic stroke (AIS) is a devastating cerebrovascular disorder associated with high morbidity, mortality, and long-term disability, where neuroinflammation serves as a central pathogenic driver mediating secondary brain injury and functional impairment. This comprehensive review synthesizes the latest advances in neuroimmune interventions for AIS over the past decade, drawing on systematic literature retrieval from PubMed, Web of Science, Embase, and Ovid Medicine. We first delineate the dual pro-inflammatory and anti-inflammatory mechanisms of key immune cells-including microglia, astrocytes, T cells, B cells, natural killer (NK) cells, monocytes, and neutrophils-in the ischemic brain. Specifically, we highlight their dynamic phenotypic polarization, intercellular crosstalk, and regulatory roles in shaping the post-ischemic immune microenvironment, which provides a theoretical basis for targeted immune interventions. Subsequently, we systematically summarize the clinical research progress on promising therapeutic strategies, encompassing traditional and novel agents such as tirofiban, methylprednisolone, natalizumab, fingolimod combined with alteplase, edaravone dexborneol, butylphthalide, JAK/STAT pathway inhibitors, ApTOLL, anakinra, and tocilizumab, as well as cell transplantation therapies. For each intervention, we analyze its efficacy, safety, underlying immune-modulatory mechanisms, and current clinical trial status. Finally, we discuss the existing challenges in clinical translation-such as suboptimal targeting efficiency, individual variability in treatment response, and unresolved safety concerns-and prospect future directions for precision immune therapy in AIS. This review offers a comprehensive and up-to-date overview of the neuroimmune landscape in AIS, providing valuable insights for researchers and clinicians engaged in stroke treatment and drug development.