# Sleep state-dependent mechanisms of seizure-induced death

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $381,951

## Abstract

ABSTRACT
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with
refractory epilepsy. The majority of SUDEP cases occur at night, during sleep, but why this is the
case in unclear. It has been proposed that a portion of these cases may be due to lack of adequate
supervision during the nighttime and relayed resuscitation efforts following a seizure. Recent
evidence suggests this is not the whole story. There are a number of physiologic changes that
occur during sleep, that may make sleep relatively intolerant to the additonal physiologic insult of a
seizure. Seizure-induced impairment of respiratory, cardiac, and arousal mechanisms have all been
implicated in SUDEP. All of these are subject to sleep state-dependent regulation. A large body of
evidence suggests that abnormalities in signaling of the neurotransmitter serotonin are important in
SUDEP. Serotonin is also regulated in a sleep state-dependent manner, and is involved in the
regulation of breathing, cardiac activity, and sleep and wakefulness, and can modulate seizures.
The primary goal of this proposal is to understand how seizures that occur during sleep become
fatal. In pursuing this goal we will test the overarching hypothesis that serotonin is involved in
regulating the state-dependence of seizure-induced death. In Aim 1 we will determine how seizures
that occur during sleep dysregulate respiratory function. In Aim 2 we will determine how seizures
that occur during sleep dysregulate arousal mechanisms. Finally, in Aim 3 we will determine how
REM sleep is protective against seizures. Completion of these aims will provide an understanding
of how seizures that occur during sleep could be fatal, and some of the findings could be directly
translatable to the clinic to aid in identification of persons at risk for SUDEP and in implemention of
novel prophylactic strategies. This work will additionally lay the groundwork for future projects
delving deeper into these mechanisms.

## Key facts

- **NIH application ID:** 10118793
- **Project number:** 3R01NS095842-05S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Gordon F Buchanan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,951
- **Award type:** 3
- **Project period:** 2016-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118793

## Citation

> US National Institutes of Health, RePORTER application 10118793, Sleep state-dependent mechanisms of seizure-induced death (3R01NS095842-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10118793. Licensed CC0.

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