Molecular Insights into the Role of Inflammation and Oxidative Stress in Epilepsy

Abstract

Epilepsy is a chronic neurological disorder manifested as unpredictable, unprovoked recurrent seizures that affect a variety of mental and physical functions. Despite the use of current anti-epileptic drugs (AEDs) about 30% of patients remain refractory, while 30-40% have associated psychiatric disturbances. A gap in successful AED search has been the lack of understanding of the processes leading to the cascade of epilepsy. Thus we tried to focus on the role of inflammation and oxidative stress in epilepsy. Epileptic seizures result in extensive release of proinflammatory factors i.e cytokines, chemokines from glial cells, thereby increasing the influx of neuronal calcium, enhancing extra neuronal glutamate concentration and decreasing potassium, resulting in decrease in seizure threshold and neurodegeneration. Prolonged seizures produce sufficient cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) which initiate a cascade of events induced by increased firing from neurons, excessive release of glutamate, activation of N-methyl-D-aspartate (NMDA) receptor, influx of cytosolic and mitochondrial calcium, increased ATP consumption and mitochondrial damage, resulting in neuronal hyperexcitation and neurodegeneration.