Microglia polarization in ischemic stroke: complex mechanisms and therapeutic interventions

Abstract

Signal transducer and activator of transcription 3 (STAT3) signaling pathway STAT3 is a potential negative regulator of inflammatory cytokine release, and phosphorylation of STAT3 (p-STAT3) is associated with microglial polarization. The STAT3 signaling pathway was activated during M2 polarization in BV-2 cells treated with panaxatriol saponins, which are traditional Chinese medicines, to treat stroke, while the inhibition of STAT3 activation by Stattic, a selective inhibitor of STAT3, reversed the inhibitory effect of panaxatriol saponins on the inflammatory response and apoptosis in microglia in an oxygen-glucose deprivation/reperfusion (OGD/R) model. [5] p-STAT3 was also increased by in vivo ischemic/reperfusion injury and in vitro OGD, while this effect was decreased by DZNep, an EZH2 inhibitor, which could promote anti-inflammatory microglial polarization. [11] In a tMCAO mouse model, Bendavia exerted antioxidative and anti-inflammatory effects, reduced matrix metalloproteinase (MMP)-9 and TNF-α protein expression levels, and reduced inflammatory microglia/macrophage activation.