TEPP-46 inhibits glycolysis to promote M2 polarization of microglia after ischemic stroke
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Updated: Aug 10, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Xiaomei Xia1, Wenli Chen2, Ting Zhou3
1Department of Rehabilitation Medicine, The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People's Hospital of Lianyungang, Lianyungang 222000 China; Department of Rehabilitation Medicine, Kangda College of Nanjing Medical University, Lianyungang 222000 China.
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.
Insights
PKM2 activation in microglia drives inflammation after ischemic stroke. TEPP-46, a PKM2 activator, reduced inflammation and injury by promoting beneficial microglial M2 polarization and inhibiting harmful glycolysis.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Ischemic stroke triggers neuroinflammation, characterized by microglial activation.
- Activated microglia in inflammatory responses often exhibit increased glycolysis metabolism.
- PKM2 expression in microglia increases during activation following ischemic stroke.
Purpose of the Study:
- To investigate the role of PKM2 in microglial activation post-ischemic stroke.
- To evaluate the therapeutic potential of TEPP-46, a PKM2 activator, in mitigating neuroinflammation and neuronal injury.
Main Methods:
- Assessed PKM2 expression in activated microglia.
- Administered TEPP-46 in vivo (tMCAO mice) and in vitro models.
- Analyzed microglial polarization, phagocytosis, neuroinflammation markers, and infarct volume.
- Investigated the mechanism involving PKM2 nuclear translocation and interaction with HIF-1α.
Main Results:
- TEPP-46 enhanced M2 microglial polarization and phagocytosis.
- TEPP-46 administration reduced neuroinflammation, neuronal injury, and infarct volume in mice.
- TEPP-46 inhibited microglial glycolysis by suppressing PKM2 nuclear translocation and PKM2-HIF-1α interaction.
Conclusions:
- PKM2 modulation in microglia presents a potential therapeutic strategy for ischemic stroke.
- TEPP-46 demonstrates efficacy in polarizing microglia from M1 to M2 phenotype, offering neuroprotection after ischemia/reperfusion injury.
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