Department of Pharmacology, National Research Centre, Cairo, Egypt.
Department of Pharmacology, National Research Centre, Cairo, Egypt.
Epilepsy Behav. 2020 Mar;104(Pt A):106893. doi: 10.1016/j.yebeh.2019.106893. Epub 2020 Jan 27.
Patients with diabetes and epilepsy are more prone to cognitive impairment, dementia, and even Alzheimer's disease. Diabetes-induced inflammatory process is one of the main contributing factors; however, the impact on seizure is not clear. The current study is aimed to examine the role of metformin and trimetazidine in the reduction of neuronal damage caused by inflammatory mediators and apoptotic factors in diabetic epileptic rodent model. Diabetic epileptic rats received orally either metformin (100 mg/kg) or trimetazidine (10 mg/kg) for 3 weeks exhibited reduced cognitive function and ameliorated the disturbed brain neurotransmission. Besides, they improved both the inflammatory status and the histopathologic alterations. Administration of metformin or trimetazidine ameliorated the deterioration in cognitive function in Morris water maze (MWM) and reduced seizure score. Furthermore, brain neurotransmitters glutamate and γ-aminobutyric acid (GABA) were reverted back to their normal values. Both treatments reduced the rise in inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), apoptotic markers nuclear factor-κB (NF-κB) and caspase-3, and improved the pathological photomicrograph of the hippocampus of diabetic epileptic rats. Such effects were closely correlated to the observed increase in the adenosine triphosphate and adenosine diphosphate (ATP/ADP) ratio and reduction of death-associated protein (DAP) and mammalian target of rapamycin (mTOR). In conclusion, the current study shed light on the potential neuroprotective role of metformin and trimetazidine in the amelioration of cognitive function via hindering inflammatory processes in diabetic epileptic rats.
患有糖尿病和癫痫的患者更容易出现认知障碍、痴呆，甚至阿尔茨海默病。糖尿病引起的炎症过程是主要的致病因素之一；然而，其对癫痫发作的影响尚不清楚。本研究旨在探讨二甲双胍和曲美他嗪在减少糖尿病癫痫啮齿动物模型中炎症介质和凋亡因子引起的神经元损伤中的作用。接受口服二甲双胍（100mg/kg）或曲美他嗪（10mg/kg）治疗 3 周的糖尿病癫痫大鼠表现出认知功能下降，并改善了受干扰的脑神经递质传递。此外，它们还改善了炎症状态和组织病理学改变。给予二甲双胍或曲美他嗪可改善 Morris 水迷宫（MWM）中的认知功能恶化，并降低癫痫评分。此外，大脑神经递质谷氨酸和γ-氨基丁酸（GABA）恢复到正常水平。两种治疗方法均降低了炎症细胞因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）、凋亡标志物核因子-κB（NF-κB）和半胱氨酸天冬氨酸蛋白酶-3的升高，并改善了糖尿病癫痫大鼠海马的病理照片。这些影响与观察到的三磷酸腺苷和二磷酸腺苷（ATP/ADP）比值增加以及死亡相关蛋白（DAP）和雷帕霉素靶蛋白（mTOR）减少密切相关。总之，本研究阐明了二甲双胍和曲美他嗪通过抑制糖尿病癫痫大鼠的炎症过程，在改善认知功能方面具有潜在的神经保护作用。
