ArticleEpilepsia2020
Progressive cardiorespiratory dysfunction in Kv1.1 knockout mice may provide temporal biomarkers of pending sudden unexpected death in epilepsy (SUDEP): The contribution of orexin.
Article in Epilepsia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- SUDEP update 2026: recent advances in experimental and clinical research.Current opinion in neurology · 2026Review
- Article
- Development and characterization of an autoresuscitation test for preclinical SUDEP models.Epilepsia · 2025Article
- Sleep EEG and respiratory biomarkers of sudden unexpected death in epilepsy (SUDEP): a case-control study.The Lancet. Neurology · 2025Article
- Article
- Sudden Unexpected Death in Epilepsy: A Narrative Review of Mechanism, Risks, and Prevention.Journal of clinical medicine · 2025Review
- Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.International journal of molecular sciences · 2025Review
- Influence of sleep on seizures and interictal epileptiform discharges in epilepsy.Encephalitis (Seoul, Korea) · 2025Article
- Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons.Neurobiology of disease · 2024Article
- Challenges and future directions of SUDEP models.Lab animal · 2024Review
- Personalization of SUDEP risk: A survey of transient subclinical comorbid changes.Epilepsy research · 2024Article
- Review
- Molecular and neural basis of pleasant touch sensation.Science (New York, N.Y.) · 2022Article
- Sudden unexpected death in epilepsy.Current opinion in neurology · 2022Review
- Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy.Frontiers in neurology · 2022Article
- The role of sleep state and time of day in modulating breathing in epilepsy: implications for sudden unexpected death in epilepsy.Frontiers in neural circuits · 2022Review
- Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation.Frontiers in cardiovascular medicine · 2022Article
- Pharmacoresponsiveness of spontaneous recurrent seizures and the comorbid sleep disorder of epileptic Kcna1-null mice.European journal of pharmacology · 2021Article
- Proceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP.Epilepsy currents · 2021Article
- Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization.Physiological reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveImmediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO
methodsHeart rate and SaO
resultsIntermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity. SIGNIFICANCE: High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.