The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress
Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency epileptogenesis phase, and the phase of spontaneous recurrent
seizures. Nowadays, an increasing attention is paid to the possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation
of mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both, physiological and pathological effects of mitochondrial function,
which can lead in neuronal cell death and consequent epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress. Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury.
The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of antiepileptic drugs are capable of covalent
binding to macromolecules which may lead to deterioration of the epileptic seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying
changes in oxidative burden, further support an important role of antioxidants as having a putative antiepileptic potential.
Keywords: Antiepileptic drugs; antioxidants; calcium; epileptogenesis; mitochondria; oxidative stress; reactive species; signalling
Document Type: Research Article
Publication date: 01 December 2012
- Current Neuropharmacology aims to provide current, timely and comprehensive reviews of all areas of neuropharmacology and related matters of neuroscience. The journal publishes reviews written by experts and leaders in the fields of molecular, cellular, and systems/behavioural aspects of neuropharmacology and neuroscience. The journal serves as a comprehensive, multidisciplinary expert forum for neuropharmacologists and neuroscientists.
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