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 status epilepticus, but also potently antiepileptogenic. There are “Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures”.
Original language | American English |
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Article number | 106410 |
Journal | Epilepsy and Behavior |
Volume | 101 |
DOIs | |
State | Published - Dec 2019 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by Epilepsy Research UK , the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602102 (EPITARGET), the German Research Foundation ( KO 3878/2-1 grant to SK), the Innovative Medizinische Forschung (IMF grant KO111715 grant to SK), and the Ursula von Euch Stiftung (fellowship to SK).
Funding Information:
This work was supported by Epilepsy Research UK, the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602102 (EPITARGET), the German Research Foundation (KO 3878/2-1 grant to SK), the Innovative Medizinische Forschung (IMF grant KO111715 grant to SK), and the Ursula von Euch Stiftung (fellowship to SK).This work was undertaken at UCLH/UCL which receives a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.
Funding Information:
This work was undertaken at UCLH/UCL which receives a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.
Publisher Copyright:
© 2019 Elsevier Inc.
Keywords
- Mitochondria
- NADPH oxidase
- Nrf2
- Oxidative stress
- Reactive oxygen species
- Status epilepticus