Reactive oxygen species in status epilepticus

There has been growing evidence for a critical role of oxidative stress in neurodegenerative disease, providing novel targets for disease modifying treatments. Although antioxidants have been suggested and tried in the treatment of epilepsy, it is only recently that the pivotal role of oxidative stress in the pathophysiology of status epilepticus has been recognized. Although conventionally thought to be generated by mitochondria, reactive oxygen species during status epilepticus and prolonged seizure are generated mainly by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (stimulated by NMDA receptor activation). Excessive production of reactive oxygen species results in lipid peroxidation, DNA damage, enzyme inhibition, and mitochondrial damage, culminating in neuronal death. Antioxidant therapy has been hampered by poor CNS penetration and rapid consumption by oxidants. However, alternative approaches such as inhibiting NADPH oxidase or increasing endogenous antioxidant defenses through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) could avoid these problems. Small molecules that increase Nrf2 activation have proven to be not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. There are “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures”. •There is substantial evidence that reactive oxygen species are generated during and after status epilepticus.•There is growing evidence that the main source of reactive oxygen species in status epilepticus is not mitochondria but rather a plasma membrane-bound enzyme, NAPH oxidase.•Reactive oxygen species significantly contribute to mitochondrial failure and neuronal death during and following status epilepticus.•Promoting the production of endogenous antioxidants through activation of the transcription factor, Nrf2, not only neuroprotects, but also potently decreases the frequency of spontaneous seizures following status epilepticus.