Seizure-Induced Oxidative Stress in Temporal Lobe Epilepsy

Abstract

An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats

“…Oxidative stress manifests as a consequence of the first seizure, which may launch the process of epileptogenesis and subsequent memory loss due to damage to hippocampus [28]. In this study, animals pretreated with SAM 100 mg/kg had shown reduction in malondialdehyde and higher glutathione level compared with the disease control group (p b 0.0001) indicating an antioxidant property of SAM in the PTZ-induced kindling model.…”

Anti-Inflammatory Small Molecules To Treat Seizures and Epilepsy: From Bench to Bedside

“…Activated NADPH oxidases (NOXs) – a family including NOX1, NOX2, NOX3, NOX4, NOX5, dual oxidase 1 (DUOX1) and DUOX2 – are a primary source of ROS via transporting electrons from intracellular NADPH, across biological membrane, and then to extracellular oxygen, generating superoxide [102, 103]. Among these seven isozymes, NOX2 is the prototype form and plays central roles in neuroinflammation, neurodegeneration and associated functional deficits in neurological conditions such as spinal cord injury [104], Parkinson’s disease [105, 106], Alzheimer’s disease (AD) [107], amyotrophic lateral sclerosis [108], multiple sclerosis [109], and epilepsy [110]. …”

Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via Nrf2/ARE Signaling

“…The environmental, genetic and epigenetic factors are interwoven in individual patients with different types of epilepsy [3]. Besides, oxidative stress and impaired autophagy contribute to epileptogenesis [4, 5]. However, there is no effective treatment to prevent the genesis or progression of seizures [6].…”