scn1ar1407x/+ Mouse on a Diet Supplemented with Whey Have Reduced Mortality Due to Promotion of Autoresuscitation
Abstract number :
2.009
Submission category :
10. Dietary Therapies (Ketogenic, Atkins, etc.)
Year :
2024
Submission ID :
1182
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Eduardo Bravo, PhD – University of Iowa
Frida Teran, MD, PhD – University of iowa
Yu-jaung Kim, PhD – University of Iowa
Angel Kelley, Student – University of Iowa
Claire Enyart, Student – University of Iowa
Toshihiro kitamoto, PhD – University of Iowa
George Richerson, MD, PhD – University of Iowa
Rationale: Patients with refractory epilepsy have a high risk of sudden unexpected death in epilepsy (SUDEP), and seizure-induced respiratory arrest (S-IRA) is thought to be the primary cause of death in many cases. The goal of the present study was to use Scn1aR1407X/+ (Dravet Syndrome, DS) mice to determine how a diet containing whey (WD) affects (1) mortality; (2) seizures; (3) S-IRA, and; (4) autoresuscitation/gasping/sighs.
Methods: DS mice were fed a regular mouse diet or a diet supplemented with 13% whey from the age they were weaned (P21) until P100. They were housed with DS littermates and video monitored to determine the rate of spontaneous death due to seizures.
A second cohort of DS mice was used to analyze interictal ventilatory parameters. A temperature telemetry probe was implanted in the peritoneal cavity at P21 in control and WD mice. The hypercapnic ventilatory response (HCVR) and the number of sighs in response to 10% hypoxia were measured 5 days later, before and after nonfatal generalized convulsive seizures were induced by hyperthermia.
A third cohort of DS mice was used to induce seizures up to modified Racine 4 (R4) by gradually increasing electrical stimulation of the hippocampus once per day for 5 days, followed by 5 days of once per day stimulation of R5 seizures, or until animals died. Data were evaluated to determine the effect of a WD on threshold for seizures, the severity of seizures, and the likelihood that R5 seizures were fatal. Between times of seizure stimulation mice were monitored in a mouse EMU for spontaneous seizures and death.
Results: A WD reduced death induced by spontaneous seizures in DS mice, increasing the survival rate at P100 from 36% for regular diet to 49% for WD. A high number of deaths occurred during the transition from day to night on regular diet, but in mice on WD the time of death was more random. Some mice on a WD were witnessed to have R5 seizures with hindlimb extension, and yet recovered and survived, which had not been seen in DS mice previously. None of the interictal ventilatory parameters were affected by a WD, with similar values of ventilation, tidal volume and frequency, as well as the HCVR and in 10% O2. After heat induced R5 seizures. During the electrical stimulation protocol, 10 of 12 mice on control diet died after an average of 4.7±0.9 days of the protocol either after stimulation of seizures (n=7) or spontaneously while mice were monitored in the EMU (n=2). The six mice on WD survived until the tenth day, at which time two died after a seizure was induced. During the 5 days that stimulation of R5 seizures was attempted, the 5 WD mice had 12 R5 seizures with hindlimb extension and ventilatory arrest,yet survived when apnea ended leading to recovery of normal eupnea. Only one mouse on control diet survived a single R5 seizure with hindlimb extension and ventilatory arrest.
Conclusions: A WD decreased mortality of DS mice by preventing death from R5 seizures, probably in part due to promotion of autoresuscitation/gasping mechanisms to recover from apnea.
Funding: NIH/NINDS U01-NS0904143 SUDEP Research Alliance
RO1NS123155 (GBR)
F31NS110333 NRSA (FAT)
Dietary Therapies (Ketogenic, Atkins, etc.)