Role of oxidative stress in epileptogenesis and potential implications for therapy

Abstract

In a state of balance between oxidants and antioxidants, free radicals play an advantageous role of "redox messengers". In a state of oxidative stress, they trigger a cascade of events leading to epileptogenesis. During this latent, free of seizures period, a cascade of neurological changes takes place and finally leads to spontaneous recurrent seizures. The main processes involved in seizure generation are: neuroinflammation, neurodegeneration with anomalous neuroregeneration and lowering seizure threshold. Time of epileptogenesis offers a unique therapeutic window to prevent or at least attenuate seizure development. Animal data indicate that some antioxidants (for instance, resveratrol) may bear an anti-epileptogenic potential.

Keywords: Epileptogenesis; Free radicals; Nitrogen species; Oxidative stress; Oxygen species.

Fig. 1

The outline of oxidative stress processes. R· free radical, O₂⁻· superoxide, NO· nitric oxide radical, ONNO· peroxynitrite, OH· hydroxyl peroxide, L· lipid radical, LOO· lipid peroxy radical, LOOH lipid hydroperoxide, LOH stable lipid alcohol, NOS nitric oxide synthase, SOD superoxide dismutase, GSH glutathione, GSSG oxidized glutathione, GPX glutathione oxidise, CAT catalase

Fig. 2

Oxidative stress and neuroinflammation in pathogenesis of seizures. ROS reactive oxygen species, RNS reactive nitrite species, TGFβ-R transforming growth factor β receptor, NMDA-R N-methyl-d-aspartate receptor, AMPA-R α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, IL-1β interleukin 1β, TNF-α tumor necrosis factor α, GLU glutamate