Environmental enrichment applied during epileptogenesis increases seizure latency and reduces serum interleukin-6 in a PTZ kindling model.

Epilepsy is a chronic neurological disorder affecting millions of individuals worldwide and is strongly associated with inflammatory processes. Although pharmacological treatment remains the first-line approach, approximately one-third of patients are refractory to available therapies. Environmental enrichment (EE) has been shown to improve cognitive function, reduce stress, and enhance neuroplasticity, suggesting its potential as a non-pharmacological strategy for neurological disorders.In this study, we investigated the effects of EE in a pentylenetetrazole (PTZ)-induced seizure model using different exposure paradigms. Animals were exposed either to EE for 30 days prior to seizure induction or during the 14-day PTZ kindling protocol. Seizure severity and latency were assessed, along with inflammatory (interleukin-6) and stress-related (cortisol) biomarkers.EE exposure during seizure induction significantly increased the latency to seizure onset compared to both the control and pre-exposed groups, with a significant Group × Session interaction across the kindling protocol and pronounced effects at later PTZ sessions. A borderline trend toward reduced seizure severity was also observed in this group, but day-specific differences did not survive correction for multiple comparisons. The EED group also exhibited significantly lower serum IL-6 levels compared with controls. No significant differences in cortisol levels were observed in serum or in the frontal cortex. Pre-exposure to EE did not produce significant protective effects on any of the outcomes evaluated.These findings suggest that EE exerts beneficial effects when applied during epileptogenic processes, particularly on the temporal progression of seizure susceptibility, and may be associated with changes in selected inflammatory markers. EE may represent a promising adjunct therapeutic strategy for epilepsy, although mechanistic studies with broader molecular characterization are still needed.