Naderi Yazdan, Sabetkasaei Masoumeh, Parvardeh Siavash, Moini Zanjani Taraneh
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Behav Pharmacol. 2017 Apr;28(2 and 3-Spec Issue):214-222. doi: 10.1097/FBP.0000000000000297.
Cerebral ischemia leads to memory impairment that is associated with loss of hippocampal CA1 pyramidal neurons. Neuroinflammation and oxidative stress may be implicated in the pathogenesis of ischemia/reperfusion damage. Minocycline has anti-inflammatory and antioxidant properties. We investigated the neuroprotective effects of minocycline in rats subjected to cerebral ischemia/reperfusion injury. Thirty male rats were divided into three groups: control, sham, and minocycline-pretreated group. Minocycline (40 mg/kg) was injected intraperitoneally immediately before surgery, and then ischemia was induced by occlusion of common carotid arteries for 20 min. Seven days after reperfusion, the Morris water-maze task was used to evaluate memory. Nissl staining was also performed to analyze pyramidal cell damage. We measured the contents of malondialdehyde and proinflammatory cytokines in the hippocampus by the thiobarbituric acid method and enzyme-linked immunosorbent assay, respectively. Microglial activation was also investigated by Iba1 immunostaining. The results showed that pretreatment with minocycline prevented memory impairment induced by cerebral ischemia/reperfusion. Minocycline pretreatment also significantly attenuated ischemia-induced pyramidal cell death and microglial activation in the CA1 region and reduced the levels of malondialdehyde and proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of ischemic rats. Minocycline showed neuroprotective effects on cerebral ischemia-induced memory deficit probably through its anti-inflammatory and antioxidant activities.
脑缺血会导致记忆障碍，这与海马CA1区锥体神经元的丧失有关。神经炎症和氧化应激可能与缺血/再灌注损伤的发病机制有关。米诺环素具有抗炎和抗氧化特性。我们研究了米诺环素对脑缺血/再灌注损伤大鼠的神经保护作用。将30只雄性大鼠分为三组：对照组、假手术组和米诺环素预处理组。在手术前立即腹腔注射米诺环素（40mg/kg），然后通过阻断颈总动脉20分钟诱导缺血。再灌注7天后，使用莫里斯水迷宫任务评估记忆。还进行了尼氏染色以分析锥体细胞损伤。我们分别通过硫代巴比妥酸法和酶联免疫吸附测定法测量海马中丙二醛和促炎细胞因子的含量。还通过Iba1免疫染色研究小胶质细胞活化。结果表明，米诺环素预处理可预防脑缺血/再灌注诱导的记忆障碍。米诺环素预处理还显著减轻了缺血诱导的CA1区锥体细胞死亡和小胶质细胞活化，并降低了缺血大鼠海马中丙二醛和促炎细胞因子（白细胞介素-1β和肿瘤坏死因子-α）的水平。米诺环素可能通过其抗炎和抗氧化活性对脑缺血诱导的记忆缺陷显示出神经保护作用。
