The effect of cyclosporin a on ischemia-reperfusion damage in a mouse model of ischemic stroke

• Published in: Neurological research (New York) 2020-09, Vol.42 (9), p.721-729
• Main Authors: Deng, Huajiang, Zhang, Shuang, Ge, Hongfei, Liu, Liang, Liu, Luotong, Feng, Hua, Chen, Ligang
• Format: Article
• Language: English
• Subjects: blood-brain barrier; Cerebral ischemia-reperfusion; cyclosporin A; ischemic stroke; PI3K/Akt
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2020.1762353

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. 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. 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. 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.