Cellular and Molecular Research Center and Department of Physiology, School of Medicine Iran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center and Department of Physiology, School of Medicine Iran University of Medical Sciences, Tehran, Iran.
J Chem Neuroanat. 2020 Nov;109:101849. doi: 10.1016/j.jchemneu.2020.101849. Epub 2020 Jul 15.
Temporal lobe epilepsy (TLE) is the most prevalent and drug-resistant form of parietal epilepsy. TLE is accompanied by neuroinflammation in the brain, which involves reactive glial cells. Metformin is an old antidiabetic drug with anti-inflammatory and neuroprotective effects. Considering the importance of inflammation in epilepsy, we have investigated the effect of metformin on astrogliosis markers as well as pro and anti-inflammatory cytokines and its effect on progranulin expression (an important neuroprotective protein in epilepsy) in a rat TLE model. TLE was induced by intracerebroventricular microinjection of kainic acid. Metformin was orally administered for two weeks before the induction of epilepsy. Astrogliosis markers (GFAP and S100B), as well as IL-1β and IL- 10 levels, were detected by ELISA. The progranulin level was measured by Western blotting and immunohistochemistry in the hippocampus. Our results showed basal levels of GFAP, S100B, and pro-inflammatory cytokine increased in the epileptic rats but were significantly ameliorated after pretreatment with metformin. However, anti-inflammatory cytokine and progranulin also increased in the pre-treated rats and metformin alone group. An increment in the progranulin level emphasizes the importance of this protein in epilepsy. Hence, metformin may exert at least some of its anti-inflammatory effects by increasing progranulin level. In sum, we have concluded that progranulin can be a key mediator in epilepsy, and the anti-inflammatory action of metformin in status epilepticus is through increasing the secretion of IL-10 and inhibiting IL-1 β and astrogliosis.
颞叶癫痫（TLE）是最常见和最耐药的顶叶癫痫形式。TLE 伴有大脑中的神经炎症，涉及反应性神经胶质细胞。二甲双胍是一种古老的抗糖尿病药物，具有抗炎和神经保护作用。鉴于炎症在癫痫中的重要性，我们研究了二甲双胍对星形胶质细胞标记物以及促炎和抗炎细胞因子的影响，以及其对癫痫中重要的神经保护蛋白颗粒蛋白前体（progranulin）表达的影响，在大鼠 TLE 模型中。TLE 通过侧脑室微量注射海人酸诱导。在癫痫发作前两周，通过口服给予二甲双胍。通过 ELISA 检测星形胶质细胞标记物（GFAP 和 S100B）以及 IL-1β 和 IL-10 水平。通过 Western blot 和免疫组织化学在海马体中测量颗粒蛋白前体的水平。我们的结果表明，癫痫大鼠的基础 GFAP、S100B 和促炎细胞因子水平升高，但在用二甲双胍预处理后显著改善。然而，抗炎细胞因子和颗粒蛋白前体在预处理大鼠和单独使用二甲双胍组中也增加。颗粒蛋白前体水平的增加强调了该蛋白在癫痫中的重要性。因此，二甲双胍通过增加颗粒蛋白前体水平可能发挥至少部分抗炎作用。总之，我们得出结论，颗粒蛋白前体可能是癫痫的关键介质，而二甲双胍在癫痫持续状态中的抗炎作用是通过增加 IL-10 的分泌和抑制 IL-1β 和星形胶质细胞增生来实现的。
