Barakat Waleed, Safwet Nancy, El-Maraghy Nabila N, Zakaria Mohamed N M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Eur J Pharmacol. 2014 Feb 5;724:43-50. doi: 10.1016/j.ejphar.2013.12.032. Epub 2013 Dec 27.
Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin.
中风是工业化国家第二大死因，也是全球成年人永久性残疾的最常见原因。中风的最终结果不仅取决于缺血核心的体积，还取决于脑肿胀、微循环受损和炎症对半暗带组织造成的继发性脑损伤程度。唯一被批准用于治疗缺血性中风的药物是重组组织型纤溶酶原激活剂（rt-PA）。本研究旨在探讨坎地沙坦（0.15 mg/kg，口服）和甘草酸（30 mg/kg，口服）对C57BL/6小鼠实验性缺血性脑损伤（大脑中动脉闭塞，MCAO）的保护作用，并与标准神经保护药物（脑蛋白水解物，7.5 mg/kg，腹腔注射）的效果进行比较。所有药物均在MCAO前30分钟和后24小时给药。坎地沙坦和甘草酸均改善了MCAO的有害影响，这表现为动物行为测试表现的改善、脑梗死、神经元变性和白细胞浸润的减少。此外，MCAO导致TLR通路的不同元件显著上调，包括TLR-2和TLR-4、Myd88、TRIF和IRF-3以及下游效应分子TNF-α、IL-1β、IL-6和NF-κB。坎地沙坦和甘草酸治疗可显著改善所有这些变化。本研究结果为坎地沙坦和甘草酸在缺血性中风管理中的应用提供了新的依据，其效果与标准神经保护药物脑蛋白水解物相当。
