Background and objective: Microglia,widely considered as the resident macrophages in the CNS,play critical role in regulating neuronal homeostasis.Under different stage,microglia either develop into M1-like microglia related toproinflammatory responses or M2-like microglia corresponding with anti-inflammatory reactions and tissue remodeling.While studies have proved the correlation between the metabolic conversion of macrophage and microglia and its activation,much less is known about how alteration of metabolism accurately regulates its polarization.Whether the function of microglia relies on its metabolism conversion under neuronal injury,like ischemic stroke,still remains unclear.Methods: Mice with middle cerebral artery occlusion(MCAO)and BV2 cells with Oxygen-glucose deprivation(OGD)were involved to detect microglia phenotype under neuronal injury.Results: IHC analysis showed augmented expression of key regulators of glycolysis including monocarboxylate transporter 1(MCT1),MCT4 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)in M1-like microglia in the ischemic penumbra after MCAO.In vitro OGD experiments also showed the significant increase of MCT1,MCT4 and PFKFB3 in mice microglia cell line BV2.After stimulation with LPS and IL4,respectively,we demonstrated that MCT1,MCT4 and PFKFB3 were specifically increased in LPS-induced M1-like primary microglia and BV2 cells.Knockdown of MCT1 and MCT4 significantly inhibited LPS-induced M1 polarization of BV2 cells.Furthermore,our results proved that MCT1 regulates M1-like polarization via up-regulation of PFKFB3 expression.We also found that knockdown of MCT1 attenuated LPS-induced production of lactate.These results suggested that MCT1 might enhance the glycolysis rate through up-regulating the expression of PFKFB3,which further accelerate LPS-induced M1-like polarization.Finally,knockdown of MCT1 attenuated microglial neurotoxicity in microglia-neuron co-cultures by suppressingthe protein levels of iNOS and proinflammatory cytokines,like IL1 β,TNF α and IL6.Conclusion: High expression of MCT1 may enhance glycolysis via PFKFB3 and further accelerate M1-like polarization and play proinflammatory roles in pathological conditions.