Microglia as Double-Edged Players in Ischemic Stroke.
Stroke has long been a leading cause of death and long-term disability worldwide. In recent years, more and more research has revealed that microglial responses to ischemic injury are highly heterogeneous and exhibit dynamic evolution over time, across brain regions, and under different metabolic states. This endows microglia with a dual regulatory role in both neurotoxicity and neuroprotection after ischemia: on one hand, they drive inflammatory responses, exacerbating secondary neuronal damage, blood-brain barrier disruption, and synaptic loss; on the other hand, they orchestrate debris clearance, vascular rebuilding, and neural repair. The traditional pro-inflammatory versus anti-inflammatory dichotomy is no longer sufficient to fully describe their complex functions. In this review we summarize recent advances in understanding the dual regulatory roles of microglia after ischemic stroke, with a focus on key mechanisms such as metabolic reprogramming, lipid metabolism regulation, inflammasome activation, and epigenetic modification. Furthermore, emerging therapeutic strategies targeting microglia and the challenges they face are discussed.