GSK-3β as a target for protection against transient cerebral ischemia

Wei Wang, Mingchang Li, Yuefei Wang, Zhongyu Wang, Wei Zhang, Fangxia Guan, Qianxue Chen, Jian Wang

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalInternational Journal of Medical Sciences
Issue number4
StatePublished - 2017


  • Blood-brain barrier
  • Ischemic stroke
  • TWS119
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Medicine(all)


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