rta-408 and Epilepsy

rta-408 has been researched along with Epilepsy* in 1 studies

Other Studies

1 other study(ies) available for rta-408 and Epilepsy

ArticleYear
KEAP1 inhibition is neuroprotective and suppresses the development of epilepsy.
    Brain : a journal of neurology, 2018, 05-01, Volume: 141, Issue:5

    Hippocampal sclerosis is a common acquired disease that is a major cause of drug-resistant epilepsy. A mechanism that has been proposed to lead from brain insult to hippocampal sclerosis is the excessive generation of reactive oxygen species, and consequent mitochondrial failure. Here we use a novel strategy to increase endogenous antioxidant defences using RTA 408, which we show activates nuclear factor erythroid 2-related factor 2 (Nrf2, encoded by NFE2L2) through inhibition of kelch like ECH associated protein 1 (KEAP1) through its primary sensor C151. Activation of Nrf2 with RTA 408 inhibited reactive oxygen species production, mitochondrial depolarization and cell death in an in vitro model of seizure-like activity. RTA 408 given after status epilepticus in vivo increased ATP, prevented neuronal death, and dramatically reduced (by 94%) the frequency of late spontaneous seizures for at least 4 months following status epilepticus. Thus, acute KEAP1 inhibition following status epilepticus exerts a neuroprotective and disease-modifying effect, supporting the hypothesis that reactive oxygen species generation is a key event in the development of epilepsy.

    Topics: Animals; Animals, Newborn; Anticonvulsants; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; Epilepsy; Excitatory Amino Acid Agonists; Gene Expression Regulation; Glutathione; Kainic Acid; Kelch-Like ECH-Associated Protein 1; Male; Membrane Potential, Mitochondrial; Mice, Transgenic; Mutation; Neuroglia; Neurons; Oxidative Stress; Rats; Rats, Sprague-Dawley; Triterpenes

2018