The effect of cyclosporin a on ischemia-reperfusion damage in a mouse model of ischemic stroke. (1st September 2020)

• Record Type: Journal Article
• Authors: Deng, Huajiang; Zhang, Shuang; Ge, Hongfei; Liu, Liang; Liu, Luotong; Feng, Hua; Chen, Ligang
• Is Part Of: Neurological research. Volume 42:Number 9(2020)
• Page Start: 721
• Page End: 729
• Publication Date: 2020-09-01
• Subjects: Cerebral ischemia-reperfusion -- cyclosporin A -- blood-brain barrier -- ischemic stroke -- PI3K/Akt; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8005
• DOI: 10.1080/01616412.2020.1762353
• Languages: English
• ISSNs: 0161-6412

Abstract

ABSTRACT: Objectives: We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism. Methods: Mice were divided equally into five groups: Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression. Results: CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased. Discussion: CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.