DOI: 10.3390/biology15211919 ISSN: 2079-7737

Dynamic Functional Remodeling of Microglia and Monocyte-Derived Macrophages After Ischemic Stroke: A Narrative Review of Traditional Chinese Medicine Mechanisms and Translational Perspectives

Xinyu Li, Cuicui Chang, Yujie Kuai, Yanju Gong, Hongfei Li, Xiang Li, Yushi Li, Hangcheng Jiang, Liangqin Shi

Ischemic stroke elicits a dynamic and heterogeneous myeloid response involving brain-resident microglia and recruited monocyte-derived macrophages, whose functional programs are shaped by lineage, spatial context, metabolic state, and disease stage. Traditional Chinese medicine (TCM) has been widely investigated for ischemic stroke, and accumulating evidence suggests that TCM-associated bioactive compounds and multi-component formulas modulate neuroinflammation, metabolism, phagocytosis, and tissue repair through these myeloid populations. However, many studies still interpret treatment effects within the M1/M2 polarization framework, which does not adequately capture post-stroke myeloid complexity. This review reframes TCM-mediated myeloid regulation in terms of dynamic functional remodeling. We examine the distinct origins, spatial heterogeneity, and stage-dependent organization of microglia and monocyte-derived macrophages, then evaluate pharmacological regulation across receptor-mediated sensing, intracellular inflammatory and metabolic signaling, and nuclear transcriptional and epigenetic control. Formula-level evidence is further considered in relation to blood–brain barrier preservation, inflammatory resolution, phagocytic clearance, neural repair, remyelination, and neurological recovery. Current evidence supports multilevel regulation but remains limited by insufficient lineage resolution, reliance on polarization-associated markers, uncertain target-cell accessibility and target engagement, and incomplete demonstration of causal myeloid mediation. Future studies integrating longitudinal, lineage-resolved, and spatial approaches with direct assessment of cellular exposure and target engagement are needed to define when, where, and through which myeloid populations TCM contributes to post-stroke repair.

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