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 journalArticle

13 Scopus citations

Abstract

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
Volume14
Issue number4
DOIs
StatePublished - 2017
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wang, W., Li, M., Wang, Y., Wang, Z., Zhang, W., Guan, F., Chen, Q., & Wang, J. (2017). GSK-3β as a target for protection against transient cerebral ischemia. International Journal of Medical Sciences, 14(4), 333-339. https://doi.org/10.7150/ijms.17514