Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy

• Published in: Neurobiology of disease Vol. 82; pp. 289 - 297
• Main Authors: Pearson, Jennifer N, Rowley, Shane, Liang, Li-Ping, White, Andrew M, Day, Brian J, Patel, Manisha
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015; Elsevier
• Subjects: Animals; Antioxidants - pharmacology; Cell Death - drug effects; Cell Death - physiology; Cognition Disorders - drug therapy; Cognition Disorders - metabolism; Cognition Disorders - pathology; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe - drug therapy; Epilepsy, Temporal Lobe - metabolism; Epilepsy, Temporal Lobe - pathology; Epilepsy, Temporal Lobe - psychology; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Learning and memory; Male; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial dysfunction; Neurology; Neuronal loss; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Nootropic Agents - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pilocarpine; Random Allocation; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Status Epilepticus - drug therapy; Status Epilepticus - metabolism; Status Epilepticus - pathology; Status Epilepticus - psychology; Learning and memory; Oxidative stress; Reactive oxygen species; Neuronal loss; Mitochondrial dysfunction; Epilepsy; Pilocarpine
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2015.07.005

Abstract 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.