title: GSK-3β inhibitors suppressed neuroinflammation in rat cortex by activating autophagy in ischemic brain injury.
abstract: 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.
authors: Department of Orthopaedics Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors: Xiaogang
authors: X
authors: Zhou
authors: Jian
authors: J
authors: Zhou
authors: Xilei
authors: X
authors: Li
authors: Chang'an
authors: C
authors: Guo
authors: Taolin
authors: T
authors: Fang
authors: Zhengrong
authors: Z
authors: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004660:Encephalitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D017628:Microglia / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3