Abstracts

Respiratory and Cardiac Dysfunction During Spontaneous Tonic-clonic Seizures Initiated in Rat Hippocampi

Abstract number : 3.009
Submission category : 1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year : 2022
Submission ID : 2204654
Source : www.aesnet.org
Presentation date : 12/5/2022 12:00:00 PM
Published date : Nov 22, 2022, 05:26 AM

Authors :
Karolina Liška, PhD – 2nd Medical Faculty, Charles University, Prague; Aakash Pant, BS – Student, Physiology, 2nd Medical Faculty, Charles University; John Jefferys, PhD, FAES – Professor, Physiology, 2nd Medical Faculty, Charles University

Rationale: We investigated the impact of repeated seizures on respiratory and cardiac function in a rat model of temporal lobe epilepsy. The relationship between seizures and cardiorespiratory function may help identify mechanisms for SUDEP.

Methods: Eleven adult male Wistar rats received an injection of tetanus toxin (List Biological Inc, 25 ng in 250 nL) into one ventral hippocampus. During the same aseptic operation under general anaesthesia we implanted an intranasal thermocouple, subcutaneous ECG leads, and electrodes in the dorsal hippocampus and/or neocortex over the contralateral dorsal hippocampus. All sensors connected to a socket cemented to the skull. After recovery from anaesthesia, continuous video-EEG recordings were made through a purpose-built preamplifier (Digitimer Ltd), wires and counterbalanced slip rings, and digitized by a 1401 signal acquisition system running SPIKE2 (CED Ltd).

Results: The first seizures appeared 3 to 10 days after injection, each lasting up to 1.5 minutes, typically in clusters lasting a few days. Ten of eleven rats developed tonic-clonic seizures. We analysed 541 tonic-clonic seizures, median duration was 49 seconds (interquartile range, 36-57 s). Of these 341 (63%) were associated with apnoeas lasting a median of 9 seconds (interquartile range, 5-13 s). These apnoeas were associated with bradyarrhythmias of similar durations, as we reported previously (DOI: 10.1111/epi.16479). In the new series, we also found cases of premature ventricular contraction during tonic-clonic seizures.

Conclusions: We developed a reliable means of monitoring respiratory airflow together with cardiac and neural electrophysiology in chronically epileptic rats. We found that the convulsive (tonic-clonic) component of seizures led to cessation of breathing, in parallel with cardiac dysfunction as reported previously. These results demonstrate a link between forebrain seizure activity and respiratory and cardiac dysfunction.

Funding: Czech Medical Research Council S-AZV/001536/2020
Basic Mechanisms