Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Brain Res. 2024 Dec 1;1844:149138. doi: 10.1016/j.brainres.2024.149138. Epub 2024 Aug 10.
Cognitive impairment is a prevalent co-morbidity associated with epilepsy. Emerging studies indicate that neuroinflammation could be a possible link between epilepsy and its comorbidities, including cognitive impairment. In this context, the roles of glial activation, proinflammatory mediators, and neuronal death have been well studied and correlated with epilepsy-associated cognitive impairment in animal studies. While recent reports have demonstrated the anti-epileptogenic and anti-convulsant actions of metformin, its effect on epilepsy associated cognitive deficit remains unknown. Therefore, the current study investigated the effect of metformin treatment on neuroinflammation, neurodegeneration, and cognitive deficits after inducing status epilepticus (SE) with lithium-pilocarpine in rats. Metformin treatment improved the hippocampal-dependent spatial and recognition memory in Morris water maze and Novel object recognition tasks, respectively. Further, metformin treatment attenuated microglial and astroglial activation, accompanied by reduced IL-1β, COX-2 and NF-ĸβ gene expression. Additionally, metformin conferred neuroprotection by inhibiting the neuronal death as assessed by Nissl staining and transmission electron microscopy. These findings suggest that metformin holds promise as a therapeutic intervention for cognitive impairment associated with epilepsy, possibly through its modulation of glial activation and neuronal survival. Further research is needed to elucidate the precise mechanisms and to assess the long-term effect of metformin in epilepsy-associated cognitive impairment.
认知障碍是与癫痫相关的常见合并症。新出现的研究表明，神经炎症可能是癫痫与其合并症（包括认知障碍）之间的一个可能联系。在这种情况下，神经胶质细胞激活、促炎介质和神经元死亡的作用已在动物研究中得到了充分研究，并与癫痫相关的认知障碍相关。虽然最近的报告表明二甲双胍具有抗癫痫发生和抗惊厥作用，但它对癫痫相关认知缺陷的影响尚不清楚。因此，目前的研究调查了二甲双胍治疗对锂-匹鲁卡品诱导癫痫持续状态（SE）后神经炎症、神经退行性变和认知缺陷的影响。二甲双胍治疗改善了 Morris 水迷宫和新物体识别任务中海马依赖性空间和识别记忆。此外，二甲双胍治疗减弱了小胶质细胞和星形胶质细胞的激活，同时降低了 IL-1β、COX-2 和 NF-ĸβ 基因的表达。此外，二甲双胍通过抑制神经元死亡（如尼氏染色和透射电子显微镜评估）发挥神经保护作用。这些发现表明，二甲双胍有望成为治疗癫痫相关认知障碍的一种治疗干预手段，可能通过调节神经胶质细胞激活和神经元存活来实现。需要进一步研究以阐明其确切机制，并评估二甲双胍在癫痫相关认知障碍中的长期效果。
