Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

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

Articles in Press

Document Type : Original Article

Authors
Leila Saremi
Mohamadreza Kordi
Amir Hossein Saffar Kohneh Quchan
Younes Sarkabood
Siroos Choobineh
Zahra Javaheri
Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran
10.22038/ijbms.2026.94597.20400
Abstract
Objective(s): 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.
Keywords
Convulsion
Epilepsy
Exercise training
Hippocampus
Inflammation
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 28 July 2026