Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

The study investigated the role of epoxyeicosatrienoic acids (EETs) in modulating GABA-mediated neurotransmission to delay seizure onset. By inhibiting the soluble epoxide hydrolase (sEH), which metabolizes EETs, through genetic deletion or direct administration, researchers found that EETs delayed seizures induced by GABA antagonists. The anticonvulsant effects were partially blocked by finasteride, an inhibitor of neurosteroid synthesis, while sEH inhibition enhanced the efficacy of allopregnanolone, a neurosteroid. The study concluded that EETs naturally suppress seizure-related excitability by modulating GABA activity, suggesting potential new treatments for convulsive disorders.