Abstract
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.
References
Nov 1, 1989·Transplantation·K KawanoM Kobayashi
Apr 1, 1995·Stroke; a Journal of Cerebral Circulation·J H GarciaX J Hu
Oct 26, 1999·Neuroscience Letters·H KitagawaK Abe
Nov 14, 2000·Neuroscience·P G SullivanS W Scheff
Mar 30, 2004·Biochemical and Biophysical Research Communications·Yoshinori SekoRyozo Nagai
Feb 3, 2006·Annals of Neurology·Victoria E O'CollinsDavid W Howells
Jul 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Annarita Di LorenzoWilliam C Sessa
Feb 11, 2011·Neurosurgery·Dzenan LulicCesar V Borlongan
May 20, 2011·Neuropeptides·Mohamed M OsmanCesar V Borlongan
May 25, 2012·Nature·Robert D BellBerislav V Zlokovic
Jan 18, 2014·Biochemical and Biophysical Research Communications·Ge YuGuoyong Hu
Jan 28, 2014·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Yun ZhouGuo-qing Zheng
Jan 1, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Peter SeizerAndreas E May
May 26, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Matthew A McMillinSharon DeMorrow
Aug 15, 2015·Toxicology Mechanisms and Methods·Nayira Ahmed Abdel BakyHazar Yacoub
Jan 30, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Michael J Haley, Catherine B Lawrence
Apr 27, 2016·Handbook of Clinical Neurology·Birgit ObermeierRichard M Ransohoff
May 11, 2018·Life Sciences·Zhiliang LiZengwu Shao
Jul 11, 2018·Acute Medicine & Surgery·Shohei MatsumotoYasuo Watanabe
Jul 19, 2018·Behavioural Neurology·Jie QuYujie Chen
Mar 8, 2019·Scientific Reports·Axel ForsseFrantz Rom Poulsen
Mar 18, 2019·Lancet Neurology·Simiao WuUNKNOWN China Stroke Study Collaboration
Apr 16, 2019·Frontiers in Immunology·Camila FloresOlivier Hermine
May 6, 2019·The Medical Journal of Australia·Bruce Cv Campbell
Jan 15, 2020·Thrombosis Research·Carme GubernMar Castellanos