eprintid: 10085309 rev_number: 28 eprint_status: archive userid: 608 dir: disk0/10/08/53/09 datestamp: 2019-11-07 16:16:09 lastmod: 2021-09-17 22:01:27 status_changed: 2019-11-07 16:18:15 type: article metadata_visibility: show creators_name: Shekh-Ahmad, T creators_name: Kovac, S creators_name: Abramov, AY creators_name: Walker, MC title: Reactive oxygen species in status epilepticus ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F81 divisions: F84 keywords: Mitochondria, NADPH oxidase, Nrf2, Oxidative stress, Reactive oxygen species, Status epilepticus note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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". date: 2019-12 date_type: published official_url: https://doi.org/10.1016/j.yebeh.2019.07.011 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1680166 doi: 10.1016/j.yebeh.2019.07.011 pii: S1525-5050(19)30577-3 lyricists_name: Abramov, Andrey lyricists_name: Shekh-Ahmad, Tawfeeq lyricists_name: Walker, Matthew lyricists_id: AABRA58 lyricists_id: TSHEK48 lyricists_id: MCWAL61 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Epilepsy & Behavior volume: 101 number: B article_number: 106410 event_location: United States issn: 1525-5069 citation: Shekh-Ahmad, T; Kovac, S; Abramov, AY; Walker, MC; (2019) Reactive oxygen species in status epilepticus. Epilepsy & Behavior , 101 (B) , Article 106410. 10.1016/j.yebeh.2019.07.011 <https://doi.org/10.1016/j.yebeh.2019.07.011>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10085309/1/Walker_AAM_ROS%20in%20neurodegeneration.pdf