Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers

Background: Neuronal hyperexcitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy. The high rate of oxidative metabolism, coupled with the low antioxidant defenses and the richness in polyunsaturated fatty acids, makes the brain highly vulnerable to free radical damage. The increased susceptibility of the brain to oxidative damage highlights the importance of understanding the role of oxidative stress in the pathophysiology of seizures. Objectives: The present review aims not only to address the link between mitochondrial dysfunction, oxidative stress and seizures, but also the modulation of the pro-oxidant/antioxidant balance following seizures and treatment with antioxidants and antiepileptic drugs. Methods: A literature review revealed that there are articles that address the role of oxidative stress and mitochondrial dysfunction in neurological disorders, including those involving different seizure models where the modulation of the pro-oxidant/antioxidant balance by seizures per se and by antioxidant agents is discussed. However, the critical role of oxidative stress in all seizure models is not uniform. Therefore, there is a need for a review article that will address all these issues together. Results/conclusions: The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of certain seizure types. The pro-oxidant/antioxidant balance is not only modulated by seizures per se, but also by antiepileptic drugs. The ability of antioxidants for reducing the seizure manifestations and the accompanying biochemical changes (i.e., markers of oxidative stress) further supports a role of free radicals in seizures and highlights a possible role of antioxidants as adjuncts to antiepileptic drugs for better seizure control.