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• W4383313294 endingPage "109653" @default.
• W4383313294 startingPage "109653" @default.
• W4383313294 abstract "Prolonged severe hypoxia follows brief seizures and represents a mechanism underlying several negative postictal manifestations without interventions. Approximately 50% of the postictal hypoxia phenomenon can be accounted for by arteriole vasoconstriction. What accounts for the rest of the drop in unbound oxygen is unclear. Here, we determined the effect of pharmacological modulation of mitochondrial function on tissue oxygenation in the hippocampus of rats after repeatedly evoked seizures. Rats were treated with mitochondrial uncoupler 2,4 dinitrophenol (DNP) or antioxidants. Oxygen profiles were recorded using a chronically implanted oxygen-sensing probe, before, during, and after seizure induction. Mitochondrial function and redox tone were measured using in vitro mitochondrial assays and immunohistochemistry. Postictal cognitive impairment was assessed using the novel object recognition task. Mild mitochondrial uncoupling by DNP raised hippocampal oxygen tension and ameliorated postictal hypoxia. Chronic DNP also lowered mitochondrial oxygen-derived reactive species and oxidative stress in the hippocampus during postictal hypoxia. Uncoupling the mitochondria exerts therapeutic benefits on postictal cognitive dysfunction. Finally, antioxidants do not affect postictal hypoxia, but protect the brain from associated cognitive deficits. We provided evidence for a metabolic component of the prolonged oxygen deprivation that follow seizures and its pathological sequelae. Furthermore, we identified a molecular underpinning of this metabolic component, which involves excessive oxygen conversion into reactive species. Mild mitochondrial uncoupling may be a potential therapeutic strategy to treat the postictal state where seizure control is absent or poor." @default.
• W4383313294 created "2023-07-07" @default.
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• W4383313294 date "2023-11-01" @default.
• W4383313294 modified "2023-10-02" @default.
• W4383313294 title "Postictal hypoxia involves reactive oxygen species and is ameliorated by chronic mitochondrial uncoupling" @default.
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• W4383313294 doi "https://doi.org/10.1016/j.neuropharm.2023.109653" @default.
• W4383313294 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37422182" @default.
• W4383313294 hasPublicationYear "2023" @default.
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