• Ping Li, Yongfang Zhang, and Hongtao Liu.
• Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, PR China; Department of Anesthesiology, The First Affiliated Hospital of Jingzhou Medical University, Jinzhou, 121001, PR China.
• Life Sci. 2019 Nov 1; 236: 116921.

AimsTo assess the role of glycogen synthase kinase-3β (GSK3β) and β-catenin in the protection of ischemic injury by dexmedetomidine (Dex).Main MethodsAdult male Sprague-Dawley rats were subjected to (middle cerebral artery occlusion, MCAO) for 2 h followed by reperfusion and Dex was administered 30min before MCAO. The neurological deficit score, cerebral infarct size and neuron survival were evaluated at 24 h after reperfusion. The expression of pAKT, pGSK3β and β-catenin in the ischemic penumbra was assayed by Western blot at 2 h after reperfusion.Key FindingsWe found that the Dex-induced increment of neuron survival in the ischemic penumbra was diminished by the PI3K inhibitor LY294002 and the β-catenin inhibitor XAV939, respectively. The increasing expression of pAKT, pGSK3β and β-catenin induced by Dex was markedly inhibited by LY294002. And the increasing expression of β-catenin in nuclei induced by Dex was markedly inhibited by XAV939. At the same time, the GSK3β inhibitor SB216763 also caused an increment of neuron survival and an increasing expression of pGSK3β and β-catenin in the ischemic penumbra.SignificanceOur data suggested that treatment with Dex reduced cerebral injury in rats exposed to cerebral ischemia-reperfusion (I/R) by the activation of the PI3K/AKT/GSK3β pathways as well the activation of downstream Wnt/β-catenin pathway. And the Wnt/β-catenin pathway may play an important role in the protection against cerebral ischemia/reperfusion injury in rats.Copyright © 2019 Elsevier Inc. All rights reserved.

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