GSK-3β inhibitors suppressed neuroinflammation in rat cortex by activating autophagy in ischemic brain injury

Biochem Biophys Res Commun. 2011 Jul 29;411(2):271-5. doi: 10.1016/j.bbrc.2011.06.117. Epub 2011 Jun 23.


Previous studies have shown that GSK-3β inhibitor could reduce infarct volume after ischemia brain injury. However, the underlying mechanisms of GSK-3β inhibitor involving neuroprotection remain poorly understood. In the present study, we demonstrated that GSK-3β inhibitor suppressed insult-induced neuroinflammation in rat cortex by increasing autophagy activation in ischemic injury. Male rats were subjected to pMCAO (permanent middle cerebral artery occlusion) followed by treating with SB216763, a GSK-3β inhibitor. We found that insult-induced inflammatory response was significantly decreased by intraperitoneal infusion of SB216763 in rat cortex. A higher level of autophagy was also detected after SB216763 treatment. In the cultured primary microglia, SB216763 activated autophagy and suppressed inflammatory response. Importantly, inhibition of autophagy by Beclin1-siRNA increased inflammatory response in the SB216763-treated microglia. These data suggest that GSK-3β inhibitor suppressed neuroinflammation by activating autophagy after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Encephalitis / etiology
  • Encephalitis / pathology
  • Encephalitis / prevention & control*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta
  • Male
  • Microglia / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley


  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3