TEPP-46 inhibits glycolysis to promote M2 polarization of microglia after ischemic stroke.

Abstract

Following an ischemic stroke, neuroinflammation is triggered and is often typified by microglial activation. According to recent research, increased glycolysis metabolism frequently occurs when microglia become activated in an inflammatory response. In this study, we found that the PKM2 expression of microglia was gradually increased during the activation of microglia in ischemic stroke. TEPP-46, the activator of PKM2, enhanced the M2 polarization and promoted phagocytosis of microglia both in vivo and in vitro. Meanwhile, TEPP-46 administration ameliorated neuroinflammation and neuronal injuries and reduced the infarct volume of tMCAO mice. Mechanistically, we demonstrated that TEPP-46 suppressed the nuclear translocation of PKM2 and the interaction of PKM2 and HIF-1α, and inhibited glycolysis of microglia. According to our research, PKM2 modulation in microglia may be a viable therapeutic approach to lessen neuroinflammation following ischemic stroke, and TEPP-46 may be able to polarize microglia from an M1 to an M2 phenotype after ischemia/reperfusion damage.