Volume 6,Issue 4
Remodeling the Ischemic Stroke Immuno-Microenvironment via Microglial Phenotypic Switching
Ischemic stroke triggers a complex cascade of sterile inflammation that critically influences neurological outcomes. While reperfusion therapies remain the standard of care, their efficacy is often undermined by secondary brain injury driven by the pro-inflammatory polarization of microglia. As the central orchestrators of the central nervous system (CNS) immuno-microenvironment, microglia exhibit dynamic plasticity, shifting between the neurotoxic M1 phenotype and the neuroprotective M2 phenotype. The pathological transition from an M2-dominant state to a sustained M1 state perpetuates neuronal death and blood-brain barrier disruption. This review comprehensively elucidates the spatiotemporal dynamics of microglial polarization and the molecular mechanisms governing this switch, with a particular focus on key signaling pathways. Furthermore, we summarize emerging therapeutic strategies, including pharmacological modulation, stem cell-derived exosomes, and stimuli-responsive nanomedicine, aimed at precisely remodeling the immuno-microenvironment. We conclude that promoting the M1-to-M2 phenotypic switch represents a promising therapeutic avenue to mitigate reperfusion injury and enhance long-term functional recovery.
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