The initial precipitating injury such as SE progresses to chronic epilepsy through multiple epileptogenic processes. Early epileptogenic events are generally characterized by neuroinflammation, neurodegeneration and abnormal neurogenesis in the hippocampus. Metformin has exhibited anti-inflammatory and neuroprotective properties in numerous studies. The current study attempts to investigate the effect of metformin on seizure-induced inflammation and neuronal degeneration, and the involvement of the mTOR pathway. Status epilepticus (SE) was induced in male Wistar rats with systemic administration of Lithium (127 mg/kg) and Pilocarpine (30 mg/kg). In test rats, Metformin 100 mg/kg or 200 mg/kg was administered orally for 7 days, followed by SE induction. Results indicate that metformin did not alter the SE profile significantly which was evident by the behavioural scoring and electroencephalogram (EEG) recordings. However, metformin 200 mg/kg attenuated the SE-induced glial activation (p < 0.01), up regulated mRNA levels of proinflammatory cytokines (p < 0.001) and chemokines (p < 0.001) and enhanced BBB permeability (p < 0.05). In addition, metformin ameliorated the insult-induced region-specific neuronal damage (p < 0.01) and restored the hippocampal neuronal density. Metformin significantly inhibited phosphorylated S6 ribosomal protein (phospho-S6rp) (p < 0.05), thus demonstrating that the beneficial effects might be partly mediated by the mTOR pathway. The study thus reiterates that mTOR signalling is one of the mechanisms involved in inflammation and neurodegeneration in early epileptogenesis following SE.

最初的诱发性损伤（如 SE）通过多个致癫痫过程发展为慢性癫痫。早期致癫痫事件通常以海马神经炎症、神经变性和异常神经发生为特征。在众多研究中，二甲双胍表现出抗炎和神经保护特性。目前的研究试图调查二甲双胍对癫痫引起的炎症和神经元变性的影响，以及 mTOR 通路的参与。全身给药锂 (127 mg/kg) 和毛果芸香碱 (30 mg/kg) 在雄性 Wistar 大鼠中诱导癫痫持续状态 (SE)。在测试大鼠中，口服二甲双胍 100 mg/kg 或 200 mg/kg 7 天，然后进行 SE 诱导。结果表明二甲双胍没有显着改变 SE 特征，这可以通过行为评分和脑电图 (EEG) 记录来证明。然而，二甲双胍 200 mg/kg 减弱了 SE 诱导的神经胶质激活（p  < 0.01)，上调促炎细胞因子 ( p  < 0.001) 和趋化因子 ( p  < 0.001) 的mRNA 水平并增强 BBB 通透性 ( p  < 0.05)。此外，二甲双胍改善了侮辱诱导的区域特异性神经元损伤（p  < 0.01）并恢复了海马神经元密度。二甲双胍显着抑制磷酸化的 S6 核糖体蛋白 (phospho-S6rp) ( p  < 0.05)，从而证明有益作用可能部分由 mTOR 通路介导。因此，该研究重申，mTOR 信号传导是参与 SE 后早期癫痫发生中炎症和神经变性的机制之一。