Brivaracetam Combined With Topiramate at Low Doses Alleviates Neurobehavioral Deficits and Oxidative Stress in a Chemoconvulsant Kindled Seizure Model

Epilepsy is a long-lasting neurological condition often associated with cognitive and behavioral comorbidities, such as anxiety, depression, and memory deficits. This study examined the therapeutic effect of topiramate (TPM) and brivaracetam (BRV), both separately and combined, using pentylenetetrazole-kindled mice. Seizure severity was visually observed during the kindling process. After that, mice underwent a series of behavioral tests to evaluate anxiety, depression, and memory performance. Subsequently, neurochemical analyses were performed to assess cholinergic activity and oxidative stress markers. The TPM + BRV group showed significantly attenuated seizure progression during all PTZ doses (<i>p</i> < 0.001), with an 88.4% reduction in seizure scores compared to monotherapies. PTZ-kindled mice showed marked behavioral impairments and biochemical imbalances, including elevated oxidative stress and acetylcholinesterase activity. While monotherapy with BRV or TPM displayed partial improvements, combined therapy provided significantly greater effects, enhancing central explorations (152% and 259.6%), sociability (195.2%), memory retention (508.4% for discrimination index and 463.9% for aversive awareness), and reducing depressive-like behaviors (52.7%-73.7%). Biochemically, the combined treatment restored antioxidant enzyme levels (SOD, CAT, and GPx) by 45%-70% and significantly lowered MDA levels (70.7%) and restored SOD activity (220.9%). These findings suggest that low-dose rational polytherapy with TPM and BRV may enhance seizure control and ameliorate associated neuropsychiatric and oxidative imbalance.