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Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy

Shekh-Ahmad, T; Lieb, A; Kovac, S; Gola, L; Wigley, WC; Abramov, AY; Walker, MC; (2019) Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy. Redox Biology , 26 , Article 101278. 10.1016/j.redox.2019.101278. Green open access

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Abstract

Many epilepsies are acquired conditions following an insult to the brain such as a prolonged seizure, traumatic brain injury or stroke. The generation of reactive oxygen species (ROS) and induction of oxidative stress are common sequelae of such brain insults and have been shown to contribute to neuronal death and the development of epilepsy. Here, we show that combination therapy targeting the generation of ROS through NADPH oxidase inhibition and the endogenous antioxidant system through nuclear factor erythroid 2-related factor 2 (Nrf2) activation prevents excessive ROS accumulation, mitochondrial depolarisation and neuronal death during in vitro seizure-like activity. Moreover, this combination therapy prevented the development of spontaneous seizures in 40% of animals following status epilepticus (70% of animals were seizure free after 8 weeks) and modified the severity of epilepsy when given to chronic epileptic animals.

Type: Article
Title: Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.redox.2019.101278
Publisher version: https://doi.org/10.1016/j.redox.2019.101278
Language: English
Additional information: © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Keywords: Epileptogenesis, Keap1-Nrf2 pathway, NADPH oxidase, Oxidative stress, Spontaneous seizures
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/10079612
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