High-intensity interval training attenuates neuroinflammation and seizure activity via miR-146a/NF-κB signaling in chronic mesial temporal lobe epilepsy.

OBJECTIVES: Regular exercise training has emerged as a non-pharmacological approach that can beneficially impact disease progression in epileptic patients, but the underlying molecular pathways remain unclear. In this study, we investigated the effects of eight weeks of high-intensity interval training (HIIT), recognized as a time-efficient form of aerobic exercise, on hippocampal neuroinflammation and seizure activity in a kainic acid rat model of chronic Mesial temporal lobe epilepsy (MTLE). MATERIALS AND METHODS: After induction of epilepsy via intrahippocampal injection of kainic acid, rats were randomly divided into 4 groups: Control, Sham, Epilepsy, and Epilepsy+HIIT. After an acclimatization period, rats in the exercise group performed 8 weeks of HIIT. The HIIT protocol consisted of running at 90% of Vmax, with active rest periods at 30% of Vmax. At the end of week 8, rats were sacrificed, and hippocampal tissue was extracted for Western blotting and real-time qPCR. RESULTS: After 8 weeks of HIIT, our data showed that IL-1β (P<0.0001), IRAK1 (P<0.0001), NF-κB (P<0.0001), and p-NMDA (P<0.0001) levels were significantly lower than in the epileptic group. Additionally, miR-146a levels were significantly lower than in the epileptic group (P<0.001). Seizure intensity also decreased in parallel with the reduction in inflammation. CONCLUSION: Our results indicate that HIIT could serve as a potent anti-inflammatory and neuroprotective tool in chronic MTLE through regulating the miR-146a/NF-κB/pNMDA pathway, highlighting that regular chronic exercise training could be a complementary therapeutic option for drug-resistant epilepsy.