Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2022 Jun;72(6):1224-1233. doi: 10.1007/s12031-022-01999-8. Epub 2022 Mar 23.
The most well-known type of focal epilepsy that is resistant to existing treatments is temporal lobe epilepsy (TLE), with seizure foci in various structures including temporal lobe, hippocampus, amygdala, entorhinal cortex, and subcortex. The most significant processes involved in the pathophysiology of temporal lobe epilepsy (TLE) are oxidative stress, inflammation, and pyroptosis. There are evidences indicating that acetyl-l-carnitine (ALC) has anti-oxidative, anti-inflammatory, and anti-pyroptotic effects. In the present study, rat model of TLE was induced by intrahippocampal kainate and animals received ALC (100 mg/kg, p.o.). ALC properly attenuated intensity of seizures and also incidence of kainate-induced status epilepticus (SE). As well, obtained findings showed that ALC can partially reverse hippocampal levels of MDA, ROS, SOD, TNFa, NF-kB, TLR4, GFAP, and caspase 1. Besides, treatment of kainate group with ALC exerted a protective effect against CA neuronal loss and abnormal mossy fiber sprouting (MFS). Conclusively, these results suggest that ALC is capable to attenuate kainate-induced SE which is somewhat mediated through its lowering of oxidative stress, neuroinflammation, and pyroptosis that are related to its neuroprotective effect.
最著名的对现有治疗方法有抗性的局灶性癫痫是颞叶癫痫（TLE），其发作灶位于包括颞叶、海马体、杏仁核、内嗅皮层和皮质下等各种结构中。颞叶癫痫（TLE）病理生理学中涉及的最重要过程是氧化应激、炎症和细胞焦亡。有证据表明乙酰左旋肉碱（ALC）具有抗氧化、抗炎和抗细胞焦亡作用。在本研究中，通过海马内海人酸诱导大鼠 TLE 模型，并用 ALC（100mg/kg，口服）处理动物。ALC 可适当减轻癫痫发作的强度，并降低海人酸诱导的癫痫持续状态（SE）的发生率。此外，研究结果表明，ALC 可部分逆转海马体 MDA、ROS、SOD、TNFa、NF-kB、TLR4、GFAP 和 caspase 1 的水平。此外，ALC 对海人酸组的治疗对 CA 神经元丢失和异常苔藓纤维发芽（MFS）具有保护作用。总之，这些结果表明，ALC 能够减轻海人酸诱导的 SE，这在一定程度上是通过降低与神经保护作用相关的氧化应激、神经炎症和细胞焦亡来实现的。
