Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Metab Brain Dis. 2019 Jun;34(3):805-819. doi: 10.1007/s11011-018-0378-0. Epub 2019 Jan 15.
Ethanol is known as an effective agent against cerebral lesions after ischemia. Modafinil is a stimulant of the central nervous system (CNS) with antioxidant properties. We assessed the neuroprotective effect of modafinil in combination with ethanol after focal cerebral ischemia. Male wistar rats weighing 280-300 g were divided into nine groups (n = 12 each group): The groups consisted of the MCAO (middle cerebral artery occlusion) group (i.e. ischemia without treatment); the vehicle group(Dimethylsulfoxide); the modafinil group including three subgroups which pretreated with Modafinil (10, 30, 100 mg/kg), respectively, for seven days prior to the induction of MCAO; the ethanol group which received 1.5g/kg ethanol at the time of reperfusion; and modafinil+ethanol group which was divided into three subgroups that received three doses of modanifil (10, 30,100 mg/kg), respectively, for seven days prior to MCAO as well as ethanol at the time of reperfusion. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of the right middle cerebral artery. Edema, infarct volume, glial scar formation (gliosis) and apoptosis were analyzed. The ethanol alone treatment (with a less significant effect), modafinil (in a dose-dependent way), and the combination of modafinil and ethanol significantly decreased the brain infarct volume, edema, apoptosis, and gliosis (P ≤ 0.05). Additionally, modafinil+ethanol mediated the restoration of aerobic metabolism and hyper-glycolysis suppress, thereby resulting in an increase in pyruvate dehydrogenase and a decrease in lactate dehydrogenase activity, respectively, which ultimately reduced oxidative reperfusion injury. These results demonstrate that pretreatment with modafinil (100 mg/kg) and modafinil+ethanol(1.5 g/kg) may prevent ischemic brain injuries.
乙醇是一种已知的有效抗脑缺血损伤的药物。莫达非尼是一种中枢神经系统（CNS）兴奋剂，具有抗氧化特性。我们评估了莫达非尼联合乙醇对局灶性脑缺血的神经保护作用。体重 280-300g 的雄性 Wistar 大鼠分为 9 组（每组 12 只）：MCAO 组（即缺血未治疗）；载体组（二甲基亚砜）；莫达非尼组，包括三个亚组，分别在 MCAO 诱导前预处理 7 天，给予莫达非尼（10、30、100mg/kg）；乙醇组，在再灌注时给予 1.5g/kg 乙醇；莫达非尼+乙醇组，分为三个亚组，分别在 MCAO 前预处理 7 天，再灌注时给予乙醇，同时给予莫达非尼（10、30、100mg/kg）。通过右侧大脑中动脉腔内 60 分钟闭塞诱导短暂性脑缺血。分析脑水肿、梗死体积、胶质瘢痕形成（胶质增生）和细胞凋亡。单独给予乙醇（作用较弱）、莫达非尼（呈剂量依赖性）以及莫达非尼和乙醇联合治疗显著降低脑梗死体积、脑水肿、细胞凋亡和胶质增生（P≤0.05）。此外，莫达非尼+乙醇介导有氧代谢的恢复和高糖酵解的抑制，分别导致丙酮酸脱氢酶活性增加和乳酸脱氢酶活性降低，从而减少氧化再灌注损伤。这些结果表明，莫达非尼（100mg/kg）预处理和莫达非尼+乙醇（1.5g/kg）预处理可能预防缺血性脑损伤。
