Seizures Cause Prolonged Impairment of Ventilation, CO Chemoreception and Thermoregulation.

Sudden unexpected death in epilepsy (SUDEP) has been linked to respiratory dysfunction, but the mechanisms underlying this association remain unclear. Here we found that both focal and generalized convulsive seizures (GCSs) in epilepsy patients caused a prolonged decrease in the hypercapnic ventilatory response (HCVR; a measure of respiratory CO chemoreception). We then studied (Dravet syndrome; DS) and (D/+) mice of both sexes, two models of SUDEP, and found that convulsive seizures caused a postictal decrease in ventilation and severely depressed the HCVR in a subset of animals.

Sudden unexpected death in epilepsy: Respiratory mechanisms.

Epilepsy is one of the most common chronic neurologic diseases, with a prevalence of 1% in the US population. Many people with epilepsy live normal lives, but are at risk of sudden unexpected death in epilepsy (SUDEP). This mysterious comorbidity of epilepsy causes premature death in 17%-50% of those with epilepsy.

A ketogenic diet protects DBA/1 and Scn1a mice against seizure-induced respiratory arrest independent of ketosis.

Patients with uncontrolled epilepsy have a high risk of sudden unexpected death in epilepsy (SUDEP). Seizure-induced respiratory arrest (S-IRA) is thought to be the determining cause of death in many cases of SUDEP. The goal of the present study was to use Scn1a (Dravet Syndrome, DS) and DBA/1 mice to determine: (1) the effect of a ketogenic diet (KD) on S-IRA and (2) the relationship between serum ketones and the protective effect of a KD.

Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy.

Objective: Sudden unexpected death in epilepsy (SUDEP) is an unpredictable and devastating comorbidity of epilepsy that is believed to be due to cardiorespiratory failure immediately after generalized convulsive seizures.

Methods: We performed cardiorespiratory monitoring of seizure-induced death in mice carrying either a p.Arg1872Trp or p.

Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Mice.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutations in the gene.

Chemosensitivity of Phox2b-expressing retrotrapezoid neurons is mediated in part by input from 5-HT neurons.

Key Points: Neurons of the retrotrapezoid nucleus (RTN) and medullary serotonin (5-HT) neurons are both candidates for central CO /pH chemoreceptors, but it is not known how interactions between them influence their responses to pH. We found that RTN neurons in brain slices were stimulated by exogenous 5-HT and by heteroexchange release of endogenous 5-HT, and these responses were blocked by antagonists of 5-HT receptors. The pH response of RTN neurons in brain slices was markedly reduced by the same antagonists of 5-HT receptors.

Medullary 5-HT neurons: Switch from tonic respiratory drive to chemoreception during postnatal development.

Serotonin (5-HT) neurons contribute to respiratory chemoreception in adult mice, but it is unclear whether they play a similar role in neonatal mice. We studied breathing during development in Lmx1b mice, which lack 5-HT neurons. From postnatal days 1-7 (P1-P7), ventilation of Lmx1b mice breathing room air was 50% of WT mice (p<0.

Serotonin neurons and central respiratory chemoreception: where are we now?

Serotonin (5-hydroxytryptamine, 5-HT) neurons are widely considered to play an important role in central respiratory chemoreception. Although many studies in the past decades have supported this hypothesis, there had been concerns about its validity until recently. One recurring claim had been that 5-HT neurons are not consistently sensitive to hypercapnia in vivo.