The Mechanism Of M2 Microglial Exosome Reduced Glial Scar Formation After Ischemic Stroke In Mice

Glia scar is major obstacle for neuronal regeneration after stroke.Approaches to promote the degradation and formation of glial scar is beneficial for functional recovery of stroke.Increasing evidence showed the interaction of microglia and astrocyte during glial scar formation after ischemic brain injury.However,whether microglia could affect glial scar formation was obscure.Our study found exosome derived from M2 microglial reduced glial scar formation and promote functional recovery after ischemic stroke.Furthermore,M2 microglial exosome enriched in miR124,one of its target gene is astrocyte proliferation gene stat3.M2 microglial exosome treatment decreased the STAT3 and GFAP expression,inhibited astrocyte proliferation in oxygen glucose deprivation injury in vitro and ischemic stroke in vivo.At the same time,M2 microglial exosome decreased Notch and increased Sox2 expression in astrocytes,which suggested that astrocyte may be transform to neuronal progenitor cell after treatment.Finally,blocking miR124 exosome derived from M2 microglia inhibited the effect of exosome on glial scar and functional recovery after stroke.Our results for the first time showed microglia regulated glial scar formation via exosome,and indicated that M2 microglial exosome treatment may be an alternative therapeutical approach for ischemic stroke.