Oxidative Stress Mechanisms in Epileptic Disorders

Epileptic disorders are characterised by recurrent neuronal hyperexcitability that disturbs redox homeostasis. Seizure activity drives excessive calcium influx and glutamate release, amplifying mitochondrial respiration and generating high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS). This oxidative onslaught damages lipids, proteins and DNA, impairs mitochondrial function and precipitates neuronal death via apoptotic and necrotic pathways. Endogenous antioxidant defences, largely orchestrated by the transcription factor Nrf2, attempt to restore balance by upregulating detoxifying enzymes, but chronic or severe seizures often overwhelm this system. Concurrent neuroinflammatory responses amplify oxidative injury through activated microglia and proinflammatory cytokines, which lower seizure threshold and fuel epileptogenesis. Lipid peroxidation products and mitochondrial DNA lesions create a vicious cycle of oxidative impairment, while disruptions in autophagy–apoptosis crosstalk further drive neuronal loss. Insights into these intertwined mechanisms point towards therapeutic strategies—ranging from Nrf2 activators and mitochondrial antioxidants to anti-inflammatory agents—that may prevent disease progression and improve patient outcomes.

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Oxidative Stress Mechanisms in Epileptic Disorders publication trend

The graph below shows the total number of articles in oxidative stress mechanisms in epileptic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that can damage cellular components.

Reactive nitrogen species (RNS): Nitrogen-containing radicals that contribute to oxidative damage in cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2): Transcription factor that regulates the expression of antioxidant and cytoprotective genes.

Oxidative phosphorylation (OXPHOS): Mitochondrial process by which cells generate ATP via the electron transport chain.

Lipid peroxidation: Oxidative degradation of lipids leading to membrane damage and cellular dysfunction.

Epileptogenesis: The process by which a normal brain becomes predisposed to recurrent seizures following an insult.

References

1. Repurposing dimethyl fumarate as an antiepileptogenic and disease-modifying treatment for drug-resistant epilepsy. Journal of Translational Medicine (2023).
2. Aminoprocalcitonin protects against hippocampal neuronal death via preserving oxidative phosphorylation in refractory status epilepticus. Cell Death Discovery (2023).
3. Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy. Cell & Bioscience (2023).