Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in mice  

作　　者：Saba Tehreem Azka Sabir Maryam Farooq Waseem Ashraf Faleh Alqahtani Tanveer Ahmad Imran Imran 

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

出　　处：《Animal Models and Experimental Medicine》2025年第2期222-238,共17页动物模型与实验医学(英文)

基　　金：The authors extended their appreciation to Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through research supporting project number(RSP2024R131).

摘　　要：Background:Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking.In this study,the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice,which is a cost-effective mechanism for screening of antiseizure drugs.Methods:The impact of lacosamide(5 mg/kg)and perampanel(0.125 mg/kg)alone and their combination was tested in corneal kindling process(3-mA current for 3 s applied twice daily for consecutive 12 days)in male BALB/c mice.Post-kindling,mice were subjected to a battery of behavioral tests assessing anxiety,memory,and depression-like behaviors.Brain tissues were then harvested for analysis of oxidative stress biomarkers.Results:Our results showed that the combination therapy of lacosamide and perampanel was more effective in reducing seizure progression than monotherapy of these drugs.Animals treated with combination therapy showed significant behavioral improvements,as reduced anxiety and depression were noticed,and their cognitive abilities were notably better compared to animals of all other groups.Moreover,biochemical assays of isolated brains from combination-treated group revealed lesser amount of oxidative stress.In addition,outcomes of dual regime were comparable to the phenytoin in seizure control but showed superior benefits in mitigation of kindling-prompted behavioral dysfunction and oxidative stress.Conclusions:This study suggests that the lacosamide and perampanel combination therapy worked noticeably better in halting the corneal kindling process in mice and improved the epilepsy-associated psychiatric disorders that might be due to antioxidant effects of both drugs.

关 键 词：behavioral studies corneal kindling LACOSAMIDE learned helplessness oxidative stress PERAMPANEL 

分 类 号：R73[医药卫生—肿瘤]