Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy

Redox Biology
T Shekh-AhmadMatthew C Walker

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.

Citations

Feb 11, 2020·Annals of the New York Academy of Sciences·Marson PutraThimmasettappa Thippeswamy
Jul 19, 2020·Medicinal Research Reviews·Claudia Bento-Pereira, Albena T Dinkova-Kostova
Oct 28, 2020·Antioxidants·Tsu-Kung LinYao-Chung Chuang
Dec 11, 2020·Oxidative Medicine and Cellular Longevity·Nan YangXiao-Yuan Mao
Sep 29, 2020·Epilepsy Research·Sookyong KohStéphane Auvin
Aug 3, 2021·Frontiers in Cellular Neuroscience·Yuxiang Cai, Zhiquan Yang
Aug 28, 2021·Antioxidants·Sara PetrilloFiorella Piemonte

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Methods Mentioned

BETA
Fluorescence

Software Mentioned

SPSS
Open Source Instruments
Graph Pad Prism

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