Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy

Tawfeeq Shekh-Ahmad, Andreas Lieb, Stjepana Kovac, L. Gola, W. Christian Wigley, Andrey Y. Abramov, Matthew C. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageAmerican English
Article number101278
JournalRedox Biology
Volume26
DOIs
StatePublished - Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Keywords

  • Epileptogenesis
  • Keap1-Nrf2 pathway
  • NADPH oxidase
  • Oxidative stress
  • Spontaneous seizures

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