Electrophysiological and histological investigation of the effect of interleukin-1 receptor antagonist on acute and PTZ kindling model of experimental epilepsy

Abstract

This study aimed to electrophysiologically and histopathologically evaluate the effects of the interleukin-1 receptor antagonist (IL-1Ra) on epileptogenesis in acute and chronic pentylenetetrazole (PTZ)-induced seizure models. A total of 42 male rats were divided into seven groups, including acute PTZ and PTZ kindling models. The effects of IL-1Ra (50 mg/kg, intraperitoneal) on seizure activity were assessed using electrocorticographic recordings, analyzing total seizure number, spike-wave number, and spike-wave duration. Histopathological examinations were performed to evaluate neuronal integrity. In the acute PTZ model, IL-1Ra administration resulted in a significant increase in the total number of seizures compared with the PTZ group (p < 0.05), while spike-wave duration was reduced. In contrast, in the PTZ kindling model, IL-1Ra decreased seizure frequency and total spike-wave duration (p < 0.05). Histopathological analysis revealed improved neuronal morphology in both the PTZ+Diazepam and PTZ+IL-1Ra groups compared with the acute PTZ group. These findings indicate that IL-1Ra exerts phase-dependent effects in experimental epilepsy. While early IL-1 receptor blockade may aggravate seizure frequency in the acute phase, it appears to attenuate epileptiform activity and provide partial neuroprotection in the chronic stage of epileptogenesis. The results underscore the importance of timing and inflammatory context in cytokine-targeted therapeutic strategies.

Keywords

• Neuroinflammation
• Epilepsy
• IL-1Ra
• Electrophysiology
• Histopathology

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