Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy

Publication date: Available online 19 July 2019Source: Redox BiologyAuthor(s): Tawfeeq Shekh-Ahmad, Andreas Lieb, Stjepana Kovac, Lukas Gola, Christian W. Wigley, Andrey Y. Abramov, Matthew C. WalkerAbstractMany 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 though NADPH oxidase inhibition and the endogenous antioxidant system through nuclear factor erythroid 2-like 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.

Source: Redox Biology - July 20, 2019 Category: Biology Source Type: research