Injury to repair: Functions of microglia and monocyte-derived cells in ischemic stroke

Anti-inflammatory microglial phenotypes promote neuronal survival, phagocytosis of necrotic debris, and blood-brain barrier repair. Pro-inflammatory microglial phenotypes, conversely, exacerbate injury through excitotoxicity, cytokine release, and vascular disruption. Initially, MdCs adopt a neuroprotective, reparative microglia-like role by phagocytizing debris and supporting repair but later shift to a pro-inflammatory phenotype, driving secondary damage. The dynamic interaction between microglia and MdCs is crucial for stroke recovery, with microglia and MdCs initially aiding in tissue repair and angiogenesis while subsequently amplifying secondary injury through pro-inflammatory phenotypes. Although various biomarkers have been proposed to differentiate microglia from MdCs and predict stroke outcomes, none have been clinically validated. Further studies are needed to identify reliable biomarkers for these distinct cell types and develop strategies to minimize secondary injury without impairing recovery after stroke.