Recombinant CXCL16 reduces brain injury by modulating microglial phenotype and attenuating apoptosis in acute ischemic stroke.

Chemokines are traditionally known for their roles in immune cell recruitment during inflammation, but emerging evidence suggests that they may also directly regulate cellular states within the central nervous system. Specifically, it remains unclear whether CXCL16 affects microglial functional states in ischemic stroke. Here, we demonstrated that recombinant CXCL16 (rCXCL16) modulated the expression of inflammation- and repair-associated markers in primary microglia and in the ischemic brain. Functionally, microglia pretreated with rCXCL16 increased HT-22 cell viability and reduced apoptosis in an indirect co-culture system. Consistently, in vivo administration of rCXCL16 reduced infarct size, restored neurobehavior performance, and suppressed apoptosis in experimental stroke in mice. These findings identify rCXCL16 as a modulator of microglial responses and suggest that its neuroprotective effects are associated with reduced inflammatory marker expression and attenuation of apoptotic injury after ischemic stroke.