Maresin 1 Alleviates Seizure Symptoms by Modulating the Crosstalk Between Inflammation and Ferroptosis.

BACKGROUND: Epilepsy is among the most common neurological disorders in children. The persistent challenges of drug-resistant epilepsy and the adverse effects associated with antiepileptic drugs highlight the need for innovative therapeutic approaches for pediatric epilepsy. Both ferroptosis and neuroinflammation have been identified as key mechanisms in the development of epilepsy. Recent studies suggest that Maresin1 may hold therapeutic promise for neurological diseases. However, the neuroprotective effects of Maresin1, particularly through the ferroptosis pathway in the context of seizures, remain insufficiently explored. OBJECTIVE: This study aimed to investigate the protective effects of MaR1 against seizures, with a focus on its regulatory role in neuroinflammation and neuronal ferroptosis. METHODS: Seizure severity was evaluated using the modified Racine scale. Cognitive abilities were assessed via the Morris Water Maze and Novel Object Recognition tests. Magnetic Resonance Imaging was used to determine hippocampal iron accumulation. Nissl staining quantified neuronal density, while Transmission Electron Microscopy examined mitochondrial ultrastructure. Western blotting was performed to analyze protein expression changes across experimental groups. RESULTS: Pretreatment with MaR1 or a ferroptosis inhibitor significantly reduced seizure severity and improved cognitive performance in epileptic mice. CONCLUSION: These findings demonstrate that MaR1 can attenuate both seizure severity and cognitive impairment in epilepsy models, potentially through modulation of neuroinflammation and the ferroptosis pathway.