期刊
NEUROBIOLOGY OF DISEASE
卷 82, 期 -, 页码 289-297出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2015.07.005
关键词
Epilepsy; Learning and memory; Oxidative stress; Reactive oxygen species; Pilocarpine; Mitochondrial dysfunction; Neuronal loss
资金
- Rocky Mountain Neurological Disorders Core Center [NIH/NS048154]
- [NIHRO1NS039587]
- [NIHRO1NS086423]
- [UO1NS083422]
- [F31NS086405]
- [F31NS077739-03]
Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. (C) 2015 Elsevier Inc. All rights reserved.
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