Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy  

作　　者：Awais Sattar Zohabia Rehman Hammad Murtaza Waseem Ashraf Tanveer Ahmad Faleh Alqahtani Imran Imran 

机构地区：[1]Department of Pharmacology,Faculty of Pharmacy,Bahauddin Zakariya University,Multan,Pakistan [2]Institut pour l'Avancee des Biosciences,Centre de Recherche UGA/INSERM U1209/CNRS 5309,Universite Grenoble Alpes,Saint Martin d'Heres,France [3]Department of Pharmacology and Toxicology,College of Pharmacy,King Saud University,Riyadh,Saudi Arabia

出　　处：《Animal Models and Experimental Medicine》2025年第2期209-221,共13页动物模型与实验医学(英文)

基　　金：The authors extend their appreciation to the Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through Research Supporting Project Number RSP2024R131.

摘　　要：Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.

关 键 词：BRIVARACETAM corneal kindling EPILEPSY neurobehavioral analyses oxidative stress RUFINAMIDE 

分 类 号：R97[医药卫生—药品]