Journal article
A ketogenic diet protects DBA/1 and Scn1aR1407X/+ mice against seizure-induced respiratory arrest independent of ketosis
Epilepsy & behavior, Vol.124, pp.108334-108334
11/2021
DOI: 10.1016/j.yebeh.2021.108334
PMCID: PMC8960470
PMID: 34600281
Abstract
•A KD decreased SUDEP incidence in Scn1aR1407X/+ mice independent of ketosis.•A KD delayed the onset of audiogenic S-IRA in DBA/1 mice independent of ketosis.•The protective effect of a KD in DBA/1 mice required continuous treatment.•Mechanisms other than formation of ketones may have a protective effect against SUDEP.
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 Scn1aR1407X/+ (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. Ketogenic diet treatment significantly decreased spontaneous seizure-induced mortality in DS mice compared to control (8% vs 39%, p = 0.0021). This protective effect was not abolished when ketosis was prevented by supplementing the KD with glucose (10% mortality, p = 0.0007). In DBA/1 mice, the latency to onset of S-IRA due to audiogenic seizures was delayed from 7.6 to 20.8 seconds by a KD on treatment day (TD) 7 compared to control (p < 0.0001), an effect that was reversed on TD14 when mice were crossed over to a control diet on TD7. β-Hydroxybutyrate (BHB) levels were significantly decreased in DBA/1 mice on a KD supplemented with glucose (p = 0.0038), but the protective effect was maintained. Our findings show that a KD decreases SUDEP in DS mice and increases the latency to audiogenic S-IRA in DBA/1 mice. In both mouse models, a KD was protective against S-IRA. This effect may be due in part to specific dietary components rather than generation of ketone bodies.
Details
- Title: Subtitle
- A ketogenic diet protects DBA/1 and Scn1aR1407X/+ mice against seizure-induced respiratory arrest independent of ketosis
- Creators
- Megan S Crotts - University of IowaYuJaung Kim - University of IowaEduardo Bravo - University of IowaGeorge B Richerson - University of IowaFrida A Teran - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Epilepsy & behavior, Vol.124, pp.108334-108334
- DOI
- 10.1016/j.yebeh.2021.108334
- PMID
- 34600281
- PMCID
- PMC8960470
- NLM abbreviation
- Epilepsy Behav
- ISSN
- 1525-5050
- eISSN
- 1525-5069
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: F31 NS110333, U01 NS090407, U01 NS090414
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984181074802771
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