Seizures Cause Prolonged Impairment of Ventilation, CO2 Chemoreception and Thermoregulation Via a Serotonergic Mechanism
Abstract number :
3.062
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2021
Submission ID :
1825619
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
George Richerson, - University of Iowa; Frida A. Teran, PhD – Postdoctoral Scholar, Neurology, University of Iowa; Rup Sainju, MD – Clinical Assistant Professor, Neurology, University of Iowa; Eduardo Bravo, PhD – Postdoctoral Research Scholar, Neurology, University of Iowa; YuJaung Kim, PhD – Neurology – University of Iowa; Alex Granner, BS – Undergraduate Research Assistant, Neurology, University of Iowa; Brian Gehlbach, MD – Clinical Professor of Neurology, Neurology, University of Iowa
Rationale: Sudden unexpected death in epilepsy (SUDEP) has been linked to serotonin (5-HT) dysfunction, but the mechanisms of this remain unclear. Here we study the effects of focal and generalized convulsive seizures (GCS) on the hypercapnic ventilatory response (HCVR) in epilepsy patients. We then study Scn1aR1407X/+ mice, a model of Dravet Syndrome (DS), to assess how seizures affect the HCVR.
Methods: Adult epilepsy patients undergoing video-EEG monitoring were tested with a rebreathing technique to measure the HCVR during an interictal period and then after a seizure. Baseline HCVR was measured in DS and WT (Scn1a+/+) littermates using whole-body plethysmography. The HCVR was then measured before and after inducing a GCS in DS mice using a heat lamp up to 42.5°C, and in WT mice before and after inducing hyperthermia to the same average temperature. In a second cohort of DS mice instrumented with telemetry temperature probes, a preictal and postictal HCVR was obtained, and core temperature was monitored for up to 24 hrs. A third cohort of DS mice received para-chlorophenylalanine (PCPA; 800 mg/kg ip) or saline once per day for four days, after which the HCVR was tested before and after heat-induced seizures. Paired t-tests were used to compare interictal and postictal HCVR slopes. Mouse data were normalized to body weight and a two-way repeated-measures ANOVA or multiple t-tests followed by Holm-Sidak’s multiple comparison tests were used as appropriate (p <0.05).
Basic Mechanisms