Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
J Stroke Cerebrovasc Dis. 2022 Aug;31(8):106576. doi: 10.1016/j.jstrokecerebrovasdis.2022.106576. Epub 2022 May 25.
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth and metabolism and integrates various signals under physiological and pathological conditions. Altered signaling of mTOR has been shown to play pathogenic roles in ischemic stroke. In the present study, the protective effect of everolimus, the selective mTOR inhibitor, in the middle cerebral artery occlusion (MCAO) model of ischemic stroke was evaluated.
Wistar rats were exposed to MCAO (30 min) followed by reperfusion for 24 h. Everolimus (100, and 500 µg/kg) was administered at the time of reperfusion, intraperitoneally. 24 h post operation, the neurological function, infarct volume, histopathological alterations and the markers of oxidative stress including superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol levels were analyzed in the peri-infarct region.
In the rats subjected to MCAO, everolimus ameliorated neurological deficits, neuronal cell loss, and infarct volume, as compared to the stroke group. Also, everolimus significantly increased SOD activity and total thiol content, while markedly decreased the MDA level, as compared to MCAO group.
Single-dose administration of everolimus significantly improved neurological deficits and inhibited cortical cell loss by enhancing redox status, subsequently protected cerebral ischemia-reperfusion injury in rats.
雷帕霉素靶蛋白（mTOR）是一种丝氨酸/苏氨酸激酶，可调节细胞生长和代谢，并在生理和病理条件下整合各种信号。已经表明，mTOR 信号的改变在缺血性中风中起致病作用。在本研究中，评估了雷帕霉素（mTOR 的选择性抑制剂）在大脑中动脉闭塞（MCAO）缺血性中风模型中的保护作用。
Wistar 大鼠暴露于 MCAO（30 分钟）后再灌注 24 小时。雷帕霉素（100 和 500μg/kg）在再灌注时腹腔内给药。手术后 24 小时，在梗塞周围区域分析神经功能、梗塞体积、组织病理学改变以及氧化应激标志物，包括超氧化物歧化酶（SOD）活性、丙二醛（MDA）和总巯基水平。
与中风组相比，MCAO 大鼠中雷帕霉素改善了神经功能缺损、神经元细胞丢失和梗塞体积。与 MCAO 组相比，雷帕霉素还显著增加了 SOD 活性和总巯基含量，同时明显降低了 MDA 水平。
单次给予雷帕霉素可通过增强氧化还原状态显著改善神经功能缺损并抑制皮质细胞丢失，从而保护大鼠脑缺血再灌注损伤。
