Respiratory Biomarkers in Kv1.1 Knockout Mice, a Model for Temporal Lobe Epilepsy
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Approximately 1:26 people have epilepsy and around 30% of those cannot effectively treat their seizures with medications, putting them at risk for Sudden Unexpected Death in Epilepsy (SUDEP). We recently demonstrated the progressive nature of epilepsy and mortality in Kv1.1 knockout (KO) mice, a model of temporal lobe epilepsy and SUDEP. We reported respiratory abnormalities in KO mice using the methacholine (MCh) challenge, indicating that increased breathing rate, apnea and respiratory failure is associated with SUDEP. We have also found that the metabolic therapy, ketogenic diet (KD), significantly reduces seizures and prolongs lifespan in KO mice. Markers of inflammation activated in toll-like receptor 4 (TLR4) pathway are associated with apnea and respiratory failure, therefore we determined whether an inflammatory pathology is apparent in lung tissue in older, KO mice that are at high-risk for SUDEP and wildtype (WT) control littermates treated with either control diet or ketogenic diet (KD). Data indicates respiratory pathology in KO mice. Increased expression of MyD88, NF-kB p65, and iNOS in bronchiole focused regions of lung tissue from high risk KO may suggest a greater susceptibility to inflammatory mediated damage and promote respiratory failure when challenged by severe seizures. Treatment with the KD protects against inflammation with reduction in inflammatory markers. Reduced inflammation may contribute to the increased longevity in the KD treated KO mice.
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