Carvedilol attenuates PTZ-induced epileptogenesis: associations with hippocampal neuroinflammation and PI3K/AKT/mTOR-related alterations.

Epileptogenesis is increasingly recognized as a multifactorial process driven by persistent neuroinflammation, oxidative stress, and dysregulated intracellular signaling, highlighting the need for therapeutic strategies that extend beyond symptomatic seizure control. The present study investigated the potential effects of prophylactic carvedilol administration on behavioral seizure progression and associated pathological alterations during the PTZ-induced kindling model, with particular emphasis on inflammatory and signaling pathways implicated in epileptogenesis. Repeated PTZ administration resulted in progressive behavioral seizure development, impaired open-field performance, hippocampal neuronal damage, reduced GABA levels, increased oxidative stress and inflammatory mediators, and altered hippocampal NLRP3 expression, along with changes in PI3K-, AKT-, and mTOR-related protein expression. Carvedilol treatment was associated with lower behavioral seizure scores, improved open-field performance, preservation of hippocampal architecture, restoration of GABA content, and attenuation of oxidative and inflammatory alterations. Carvedilol treatment was also accompanied by reduced NLRP3 levels and changes in PI3K/AKT/mTOR-related measurements. These findings demonstrate associations between carvedilol treatment and multiple pathological processes during PTZ-induced kindling, but do not establish direct pathway-specific causality.