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. 2020 Jan 25:316:108915.
doi: 10.1016/j.cbi.2019.108915. Epub 2019 Dec 6.

Zafirlukast protects blood-brain barrier integrity from ischemic brain injury

Chaosheng Zeng  1 , Desheng Wang  1 , Cong Chen  2 , Lin Chen  1 , Bocan Chen  1 , Li Li  1 , Min Chen  1 , Huaijie Xing  1
Affiliations

Zafirlukast protects blood-brain barrier integrity from ischemic brain injury

Chaosheng Zeng et al. Chem Biol Interact. .

Abstract

Stroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the cysLT1R antagonist zafirlukast both in vivo and in vitro using a middle cerebral artery occlusion (MCAO) mouse model and human brain microvascular endothelial cells (HBMVECs). In vivo, we found that zafirlukast pretreatment could reduce MCAO-induced increased brain permeability by rescuing the expression levels of the tight junction proteins occludin and ZO-1. In vitro, we found that zafirlukast could suppress the increase in endothelial monolayer permeability induced by OGD/R via rescue of occludin and ZO-1 expression; additionally, we found that zafirlukast prevented OGD/R-induced degradation of the extracellular matrix via inhibition of MMP-2 and MMP-9 expression. Finally, we found that zafirlukast could also inhibit OGD/R-induced activation of the critical proinflammatory regulator NF-κB by preventing phosphorylation and nuclear translocation of p65 protein. Together, our findings demonstrate a promising role for zafirlukast in preventing damage induced by ischemic stroke and reperfusion injury.

Keywords: Brain endothelial cells; Brain permeability; NF-κB; Tight junction; ZO-1; Zafirlukast.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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