臨床および実験神経免疫学ジャーナル

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Targeting Soluble Epoxide Hydrolase for Temporal Lobe Epilepsy

Yu-Wen Hung, Yung-Yang Lin

Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. It remains unknown regarding the mechanisms for epilepsy formation. Prolonged seizures trigger significant neuroinflammatory responses in experimental and human temporal lobe epilepsy, which have been speculated to be mediating the epileptogenesis. Currently, extensive evidence suggests that anti-inflammatory approaches might offer a promising alternative therapeutic strategy especially when antiepileptic medications are ineffective. By diminishing the anti-inflammatory activities of epoxyeicosatrienoic acids (EETs), soluble epoxide hydrolase (sEH) has been considered a potential therapeutic target for epileptic seizures. Here we review evidences concerning the relevance of neuroinflammarion to the pathophysiology of epilepsy, the physiological functions of EETs-sEH metabolism in central nervous system, and the linkage of EET-sEH pathway to neuroinflammation and neuromodulation. Several contemporary studies have contributed to defining the importance of sEH inhibition in modulating inflammatory responses and abnormal hyperexcitability related to epilepsy. Notwithstanding some discrepancies have been noted between different experimental models or between pharmacological inhibition and genetic deletion of sEH, the involvement of sEH in the generation and progression of epilepsy suggests that sEH may be an attractive target for therapeutic intervention.