article · Scientific Reports
Epileptogenesis involves complex biological changes, including ongoing brain inflammation, oxidative damage, and dysregulated intracellular signalling pathways. Using a pentylenetetrazole kindling model, repeated stimulation produced worsening seizure behaviour, impaired open-field performance, hippocampal tissue damage, depleted GABA levels, and heightened inflammatory and oxidative markers, alongside alterations in NLRP3 and PI3K, AKT, and mTOR pathways. Prophylactic administration of carvedilol lowered seizure severity scores and improved behavioural performance in open-field tests. The treatment was also linked to preserved hippocampal architecture, restored GABA concentrations, and reduced oxidative stress and inflammatory mediators, including lower NLRP3 levels. Although carvedilol was associated with measurable changes across these neurochemical and behavioural markers, the results demonstrate therapeutic associations rather than proving direct, pathway-specific causality.
Current epilepsy treatments primarily address symptoms rather than the underlying disease development. By demonstrating that carvedilol can alleviate seizure severity, suppress neuroinflammation, and protect brain tissue in an animal model, this work highlights potential pathways for developing therapies that could alter the progression of seizure disorders beyond standard symptom control.
The findings suggest potential avenues for drug repurposing, where carvedilol could inform future neuroprotective therapies aimed at slowing seizure progression. The immediate users of this work are neuropharmacology researchers and early-stage drug development teams exploring anti-epileptogenic targets. Because the evidence is derived entirely from an animal kindling model, the work represents early-stage discovery that remains distant from clinical use.
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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.
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DOI: 10.1038/s41598-026-67306-2
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