Abstract
One of the most important characteristics of the brain compared to other organs is its elevated metabolic demand. Consequently, neurons consume high quantities of oxygen, generating significant amounts of reactive oxygen species (ROS) as a by-product. These potentially toxic molecules cause oxidative stress (OS) and are associated with many disorders of the nervous system, where pathological processes such as aberrant protein oxidation can ultimately lead to cellular dysfunction and death. Epilepsy, characterized by a long-term predisposition to epileptic seizures, is one of the most common of the neurological disorders associated with OS. Evidence shows that increased neuronal excitability—the hallmark of epilepsy—is accompanied by neuroinflammation and an excessive production of ROS; together, these factors are likely key features of seizure initiation and propagation. This review discusses the role of OS in epilepsy, its connection to neuroinflammation and the impact on synaptic function. Considering that the pharmacological treatment options for epilepsy are limited by the heterogeneity of these disorders, we also introduce the latest advances in anti-epileptic drugs (AEDs) and how they interact with OS. We conclude that OS is intertwined with numerous physiological and molecular mechanisms in epilepsy, although a causal relationship is yet to be established.
Highlights
Epilepsy is a group of heterogeneous diseases affecting 50 million individuals worldwide across all ages and ethnicities [1,2]
It may be that the degree of pathological oxidative stress (OS) in epilepsy varies according to the cause and the severity of the episodes, explaining some of the apparent inconsistencies described in the literature
Despite significant advances in the genetics of epilepsy, the heterogeneity of disorders characterised by seizures continues to hamper the search for novel therapeutic strategies that will target multiple patient groups
Summary
Epilepsy is a group of heterogeneous diseases affecting 50 million individuals worldwide across all ages and ethnicities [1,2]. Epilepsy is classified initially as generalised or partial, with further sub-classifications according to the seizure type and duration, overall severity and physical consequences to the patient [4]. To add to this complexity, differences in the underlying cause, neurophysiological and neuroimaging characteristics and comorbidities are major players in disease prognosis and management [5]. It is estimated that neurons consume 75–80% of energy produced in the brain [14]; the brain is a prime target for OS To add another layer of complexity, epilepsy and OS are linked to neuroinflammation [15]. We discuss classical and new anti-epileptic drugs (AEDs) and their interference with OS, as well the influence of neuroinflammation and new strategies for the clinical management of epilepsy
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