Astrogliosis in the Brainstem of a Preclinical SUDEP Model: Impact of Ketogenic Diet Treatment
Abstract number :
3.507
Submission category :
2. Translational Research / 2D. Models
Year :
2023
Submission ID :
1494
Source :
www.aesnet.org
Presentation date :
12/4/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Christy Heimbrecht, BS – Creighton University School of Medicine
Reid Morrissey, BS – Creighton University School of Medicine; Kristina Simeone, PhD – Creighton University School of Medicine
Rationale: Epilepsy is a chronic neurological condition that is characterized by unprovoked seizures. Sudden unexpected death in epilepsy (SUDEP) is a poorly characterized phenomenon which is more prevalent in the approximately 35% of epilepsy patients who have refractory epilepsy, resulting in 4.2 cases of SUDEP per 1000 patients. Evidence from previous studies suggests that patients with these refractory seizures may have damage in the brain’s respiratory centers, leading to a series of events promoting hypoxic and hypercapnic fluctuations in blood gasses, including generalized convulsive seizures and apnea, from which they were unable to autoresuscitate ultimately leading to terminal apnea. Data indicate astrogliosis in respiratory centers in the brainstem of the Kv1.1 KO mice, a preclinical model of SUDEP, suggesting that this increased gliosis could lead to respiratory problems in epileptic mice. Ketogenic diet (KD) consists of a diet of high fat, low carbohydrate and has historically been utilized for those patients with refractory seizure unresponsive to pharmacotherapy. This study aims to examine whether KD treatment attenuates brainstem astrogliosis.
Methods: Kv1.1 and WT control mice were treated with either standard or ketogenic diet for two weeks. Following transcardial perfusion, brainstem sections were immunolabeled with GFAP to assess astrogliosis using immunohistochemistry.
Results: Previous studies found widespread astrogliosis in brainstem regions of mice that have had chronic seizures for multiple months. Here, we assessed an early timepoint and found selective astrogliosis in injury susceptible brainstem regions, including the locus coeruleus, nucleus ambiguous and raphe obscurus. Treatment with the ketogenic diet for two weeks attenuated astrogliosis in the locus coeruleus, but not the other regions.
Conclusions: Ketogenic diet treatment attenuated astrogliosis in select brainstem regions. Future studies will investigate whether long-term treatment will benefit additional brainstem regions.
Funding: NIH NINDS R01 (KAS)
Translational Research