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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.
AuthorsS Williams, N Hamil, A Y Abramov, M C Walker, S Kovac
JournalNeuroscience (Neuroscience) Vol. 303 Pg. 160-5 (Sep 10 2015) ISSN: 1873-7544 [Electronic] United States
PMID26162241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Sulfones
  • 4-(2-aminoethyl)benzenesulfonylfluoride
  • NADPH Oxidases
  • Glutathione
Topics
  • Animals
  • Brain (drug effects, enzymology, metabolism)
  • Cell Death (drug effects)
  • Cells, Cultured
  • Glutathione (analysis)
  • Male
  • NADPH Oxidases (antagonists & inhibitors)
  • Neurons (drug effects, enzymology, metabolism)
  • Neuroprotective Agents (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (antagonists & inhibitors, metabolism)
  • Status Epilepticus (enzymology, metabolism)
  • Sulfones (pharmacology)

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