Reactive oxygen species in status epilepticus

Epilepsy & Behavior : E&B
T Shekh-AhmadM C Walker

Abstract

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 sta...Continue Reading

Citations

Sep 1, 2020·Pharmacological Reports : PR·Kinga K Borowicz-Reutt, Stanisław J Czuczwar
Sep 6, 2020·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Suchitra Joshi, Howard P Goodkin
Oct 28, 2020·Antioxidants·Tsu-Kung LinYao-Chung Chuang
Jan 12, 2021·Frontiers in Neuroscience·Shuang ChenQifu Li
Aug 8, 2021·Environmental Science and Pollution Research International·Hagar N Abd AllahEman S Abdel-Reheim
Aug 28, 2021·Antioxidants·Sara PetrilloFiorella Piemonte

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