Department of Pharmacology, Research Block-B, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160012, India.
Inflammopharmacology. 2018 Aug;26(4):1125-1131. doi: 10.1007/s10787-018-0478-9. Epub 2018 Apr 11.
Epilepsy, a disease of the brain, is one of the most common serious neurological conditions. It is associated with a group of processes which alter energy metabolism, interrupt cellular ionic homeostasis, cause receptor dysfunction, activate inflammatory cascade, alter neurotransmitter uptake and result in neuronal damage. The increasing knowledge and understanding about the basis of neuronal changes in epilepsy lead to investigate the mechanistic pathway of neuroprotective agents in epilepsy. With this background, the present study is designed to reveal the molecular and biochemical mechanisms involved in the neuroprotective potential of zonisamide in epilepsy.
Seizure-induced neuronal damage was produced by maximal electroshock seizures in animals. The oxidative stress and neuroinflammatory and apoptotic markers were assessed in the brain tissue of animals.
The present findings revealed that zonisamide treatment prevented the development of seizures in animals. Seizures-induced free radicals production and neuroinflammation were markedly ameliorated by zonisamide administration. In conclusion, the present study demonstrated the mechanisms behind the strong neuroprotective potential of zonisamide against seizures by attenuating the oxidative stress, inflammatory cascade and neuronal death associated with progression of seizures. It can be further developed as a neuroprotective agent for epilepsy and other neurodegenerative disorders.
癫痫是一种脑部疾病，是最常见的严重神经系统疾病之一。它与一系列改变能量代谢、破坏细胞离子平衡、导致受体功能障碍、激活炎症级联反应、改变神经递质摄取并导致神经元损伤的过程有关。对癫痫中神经元变化基础的认识不断提高，促使人们研究神经保护剂在癫痫中的作用机制。基于这一背景，本研究旨在揭示佐尼沙胺在癫痫中的神经保护潜力所涉及的分子和生化机制。
通过最大电休克诱发动物癫痫发作，产生癫痫诱导的神经元损伤。评估动物脑组织中的氧化应激和神经炎症及凋亡标志物。
本研究发现佐尼沙胺治疗可预防动物癫痫发作。佐尼沙胺的给药显著改善了癫痫发作引起的自由基生成和神经炎症。总之，本研究通过减轻与癫痫进展相关的氧化应激、炎症级联和神经元死亡，证明了佐尼沙胺对癫痫发作具有强大的神经保护潜力的机制。它可以进一步开发为癫痫和其他神经退行性疾病的神经保护剂。
