Introduction:As a chronic neurological disorder, epilepsy is affected by social stress, which is one of the numerous complications in societies. In addition to medication, enriched environment (EE) and exercise are among the complementary strategies in the treatment of epilepsy. Oxidative stress, which potentially can activate the inflammatory pathways, is one of the causes of this disorder. So, we tried to examine thoroughly the beneficial impacts of EE and exercise on neuroinflammation in epileptic rats. Methods: Male Wistar rats were divided into five groups of twelve rats each, including: a control group, a group induced with pilocarpine to simulate epilepsy, an epileptic group subjected to social stress, an epileptic group placed in an enriched environment, and an epileptic group subjected to an exercise regimen. The impact of social stress, enriched environment, and exercise on oxidative stress biomarkers was investigated through TBARS spectrophotometric test and the gene expression of NLRP3, Caspase-1, IL18, and IL1β were evaluated through real-time PCR method. Results: Epilepsy and social stress caused a reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) (p<0.05). Moreover, they resulted in an enhancement of plasma malondialdehyde (MDA), NLRP3, Caspase-1, interleukin-18 (IL18), and IL1β gene expression (p<0.05). Exercise increased the GPx and diminished the expression of Caspase-1 and IL 18 inflammatory genes (p<0.05). Accordingly, EE enhanced the SOD and GPx antioxidant indicators and reduced proinflammatory gene expression. Conclusion: In this research, social stress resulted in elevated levels of oxidative markers and upregulation of inflammatory gene expression. EE and regular exercise improved the situation.
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