Effect of prednisolone in a kindling model of epileptic seizures in rats on cytokine and intestinal microbiota diversity.

ABSTRACT

Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures. Epileptic seizures can be initiated and facilitated by inflammatory mechanisms. As the dysregulation of the immune system would be involved in epileptogenesis, it is suggested that anti-inflammatory medications could impact epileptic seizures. These medications could potentially have a side effect by altering the structure and composition of the intestinal microbiota. These changes can disrupt microbial homeostasis, leading to dysbiosis and potentially exacerbating intestinal inflammation. We hypothesize that prednisolone may affect the development of epileptic seizures, potentially influencing the diversity of the intestinal microbiota and the regulation of pro-inflammatory cytokines in intestinal tissue. This study aimed to evaluate the effects of prednisolone treatment on epileptic seizures and investigate the effect of this drug on the bacterial diversity of the intestinal microbiota and markers of inflammatory processes in intestinal tissue. We used Male Wistar rat littermates (n = 31, 90-day-old) divided into four groups positive control treated with 2 mg/kg of diazepam (n = 6), negative control treated with 0.9 g% sodium chloride (n = 6), and the remaining two groups were subjected to treatment with prednisolone, with one receiving 1 mg/kg (n = 9) and the other 5 mg/kg (n = 10). All administrations were performed intraperitoneally (i.p.) over 14 days. To induce the chronic model of epileptic seizures, we administered pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. Seizure latency (n = 6 - 10) and TNF-α and IL-1ß concentrations from intestinal samples were measured by ELISA (n = 6 per group), and intestinal microbiota was evaluated with intergenic ribosomal RNA (rRNA) spacer (RISA) analysis (n = 6 per group). The prednisolone treatment demonstrated an increase in the latency time of epileptic seizures and TNF-α and IL-1ß concentrations compared to controls. There was no statistically significant difference in intestinal microbiota diversity between the different treatments. However, there was a strong positive correlation between microbial diversity and TNF-α and IL-1ß concentrations. The administration of prednisolone yields comparable results to diazepam on increasing latency between seizures, exhibiting promise for its use in clinical studies. Although there were no changes in intestinal microbial diversity, the increase in the TNF-α and IL-1ß cytokines in intestinal tissue may be linked to immune system signaling pathways involving the intestinal microbiota. Additional research is necessary to unravel the intricacies of these pathways and to understand their implications for clinical practice.