CDDO-EA Attenuates Acute Seizures and Suppresses Post-Status Epilepticus Epileptogenesis

We aimed to investigate the acute anticonvulsant and long-term antiepileptogenic effects of the synthetic triterpenoid CDDO-EA in complementary experimental models of epilepsy. CDDO-EA was evaluated in the pentylenetetrazol seizure model and a kainic acid-induced post-status epilepticus model. Acute seizure severity, latency to generalized seizures, oxidative stress and inflammatory markers, spontaneous recurrent seizures, and hippocampal neuronal survival were assessed. In the pentylenetetrazol model, CDDO-EA pretreatment reduced maximal seizure severity and prolonged the latency to stage V-VI seizures. These effects were associated with decreased inflammatory cytokine levels and malondialdehyde levels, alongside increased superoxide dismutase and catalase activities 24 h after pentylenetetrazol administration. In the post-status epilepticus model, two weeks of CDDO-EA treatment significantly delayed the onset of spontaneous recurrent seizures and produced sustained reductions in weekly seizure frequency and cumulative seizure burden. Histological analysis demonstrated greater neuronal preservation in the hippocampal CA1 and CA3 regions of CDDO-EA-treated animals compared with vehicle controls. CDDO-EA exerts both anticonvulsant and disease-modifying effects by attenuating seizure severity, restoring redox-inflammatory homeostasis, preserving hippocampal neurons, and suppressing epileptogenesis after status epilepticus, supporting its therapeutic potential as a novel strategy for epilepsy.