Ralta Arti, Prakash Ajay, Kumar M Praveen, Kumar Rohit, Sarma Phulen, Bhatia Alka, Medhi Bikash, Chakrabarti Amitava
Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER) Chandigarh, India.
Basic Clin Neurosci. 2023 Jan-Feb;14(1):155-166. doi: 10.32598/bcn.2021.3154.1. Epub 2023 Jan 1.
Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model.
PTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, 500 mg\kg, pergolide 2 mg/kg, C. paniculatus (250 mg\kg)+ Pergolide (1 mg/kg), and (250 mg\kg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed.
(500 mg/kg) alone and in combination ( (250 mg\ kg)+ pergolide (1 mg/kg) and (250 mg\kg)+ SVA (100 mg/kg)) significantly (P<0.05) reduced the seizure score, mean latency time, and distance traveled in the MWM. However, no significant effect was seen in GPS. Biochemical analysis showed elevated antioxidant markers, namely GSH, CAT, and SOD, and also elevated dopamine levels. and its combination also significantly (P<0.05) protected against neuronal loss in the hippocampus and frontal cortex evidenced by H&E staining.
alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits.
认知缺陷是癫痫常见的合并症之一。本研究评估了种子提取物对戊四氮（PTZ）诱导的化学点燃模型后癫痫严重程度和认知缺陷的影响。
通过每天给予30mg/kg的亚惊厥剂量PTZ，持续四周来建立PTZ点燃模型。诱导四周后，在注射PTZ（30mg/kg）前30分钟给予以下治疗，即丙戊酸钠（SVA）200mg/kg、500mg/kg、培高利特2mg/kg、圆锥叶大戟（250mg/kg）+培高利特（1mg/kg）以及圆锥叶大戟（250mg/kg）+SVA（100mg/kg），持续接下来的14天。评估神经行为参数，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽（GSH）和多巴胺水平，并进行莫里斯水迷宫试验（MWM）和握力试验（GPS）。对海马角回（CA1）、CA2、CA3、齿状回（DG）和额叶皮质进行苏木精-伊红（H&E）染色。
单独使用（500mg/kg）以及联合使用（圆锥叶大戟（250mg/kg）+培高利特（1mg/kg）和圆锥叶大戟（250mg/kg）+SVA（100mg/kg））均显著（P<0.05）降低了癫痫发作评分、平均潜伏时间以及在MWM中的游动距离。然而，在GPS中未观察到显著影响。生化分析显示抗氧化标志物GSH、CAT和SOD升高，多巴胺水平也升高。H&E染色证明，单独使用以及联合使用还显著（P<0.05）防止了海马体和额叶皮质中的神经元损失。
单独使用以及与其他药物联合使用可能具有治疗癫痫和相关认知缺陷的潜力。
