title: Status epilepticus results in persistent overproduction of reactive oxygen species, inhibition of which is neuroprotective.
abstract: Epilepsy and seizure activity result in the generation of reactive oxygen species (ROS), which contribute to seizure-induced neuronal damage. Recent in vitro evidence indicates that NADPH oxidase contributes significantly to seizure-induced ROS. We further tested this in rat glio-neuronal cultures and in ex vivo chronic epileptic rat brain tissue using live cell-imaging techniques. Here, we show that ROS are upregulated in chronic epilepsy and that ROS production contributes to cell death, which is seen after status epilepticus (SE) and chronic seizures. Inhibition of ROS production by AEBSF, a NADPH oxidase inhibitor, markedly reduced seizure-induced cell death in the perforant path model of epilepsy. These findings demonstrate a critical role for ROS, generated by NADPH oxidase, contributing to seizure-induced cell death. These findings point to NADPH oxidase inhibition as a novel treatment strategy to prevent brain injury in SE and chronic epilepsy.
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Hamil
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: A Y
authors.initials: AY
authors.lastname: Abramov
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Walker
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, UK; Department of Neurology, University of Muenster, Muenster, Germany. Electronic address: stjepana.kovac.09@ucl.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Kovac
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000032:analysis; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013226:Status Epilepticus / Q000201:enzymology / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D019255:NADPH Oxidases; D005978:Glutathione
keywords: NADPH oxidase; cell death; reactive oxygen species; seizures; status epilepticus