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

9 Citations (Scopus)

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

Fingerprint

Glycogen Synthase Kinase 3
Transient Ischemic Attack
Catenins
Middle Cerebral Artery Infarction
Stroke
Reperfusion Injury
Blood-Brain Barrier
Cerebrovascular Circulation
Wnt Signaling Pathway
Tight Junctions
Brain Edema
Tissue Plasminogen Activator
Neurologic Manifestations
Dimethyl Sulfoxide
Intraperitoneal Injections
Brain Ischemia
Action Potentials
Cause of Death
Permeability
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

GSK-3β as a target for protection against transient cerebral ischemia. / Wang, Wei; Li, Mingchang; Wang, Yuefei; Wang, Zhongyu; Zhang, Wei; Guan, Fangxia; Chen, Qianxue; Wang, Jian.

In: International Journal of Medical Sciences, Vol. 14, No. 4, 2017, p. 333-339.

Research output: Contribution to journalArticle

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, vol. 14, no. 4, pp. 333-339. https://doi.org/10.7150/ijms.17514
Wang, Wei ; Li, Mingchang ; Wang, Yuefei ; Wang, Zhongyu ; Zhang, Wei ; Guan, Fangxia ; Chen, Qianxue ; Wang, Jian. / GSK-3β as a target for protection against transient cerebral ischemia. In: International Journal of Medical Sciences. 2017 ; Vol. 14, No. 4. pp. 333-339.
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