29 March 2017
Int J Med Sci 2017; 14(4):333-339. doi:10.7150/ijms.17514
GSK-3β as a target for protection against transient cerebral ischemia
1. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China;
Stroke remains the leading cause of death and disability worldwide. This fact highlights the need to search for potential drug targets that can reduce stroke-related brain damage. We showed recently that a glycogen synthase kinase-3β (GSK-3β) inhibitor attenuates tissue plasminogen activator-induced hemorrhagic transformation after permanent focal cerebral ischemia. Here, we examined whether GSK-3β inhibition mitigates early ischemia-reperfusion stroke injury and investigated its potential mechanism of action. We used the rat middle cerebral artery occlusion (MCAO) model to mimic transient cerebral ischemia. At 3.5 h after MCAO, cerebral blood flow was restored, and rats were administered DMSO (vehicle, 1% in saline) or GSK-3β inhibitor TWS119 (30 mg/kg) by intraperitoneal injection. Animals were sacrificed 24 h after MCAO. TWS119 treatment reduced neurologic deficits, brain edema, infarct volume, and blood-brain barrier permeability compared with those in the vehicle group. TWS119 treatment also increased the protein expression of β-catenin and zonula occludens-1 but decreased β-catenin phosphorylation while suppressing the expression of GSK-3β. These results indicate that GSK-3β inhibition protects the blood-brain barrier and attenuates early ischemia-reperfusion stroke injury. This protection may be related to early activation of the Wnt/β-catenin signaling pathway.
Keywords: blood-brain barrier, ischemic stroke, Wnt/β-catenin signaling, TWS119
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How to cite this article:
Wang W, Li M, Wang Y, Wang Z, Zhang W, Guan F, Chen Q, Wang J. GSK-3β as a target for protection against transient cerebral ischemia. Int J Med Sci 2017; 14(4):333-339. doi:10.7150/ijms.17514. Available from http://www.medsci.org/v14p0333.htm