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

Yueying Liu,1,* Shengjie Xu,1,* Yufan Luo,1,* Xue Xiao,1 Xiaofan Jiang,1 Wei Xiao,1 Ruijin Xie,1 Xianhui Deng,2 Zhen Li,3 Yingsi Cao,1 Yuanjin Chang,1 Dongqin Wu,1 Hua Xu,1 Wenjing Zhao4 1Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 2Department of Neonatology, Jiangyin People’s Hospital of Nantong University, Wuxi, People’s Republic of China; 3Department of Child Health and Development, Center for Disease Control and Prevention of Yangzhou, Yangzhou, People’s Republic of China; 4Department of Anesthesiology, Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjing Zhao, Department of Anesthesiology, Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, People’s Republic of China, Email [email protected]: 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.Keywords: epilepsy, Maresin1, neuroinflammation, ferroptosis