Authors :
Presenting Author: Karolina Liska, PhD – 2LF, Charles University
Aakash Pant, Student – Student, Physiology, 2LF, Charles University; Brano Krajcovic, PhD – Research Associate, Physiology, 2LF, Charles University; John Jefferys, PhD FAES FMedSc – Professor, Physiology, 2LF, Charles University
Rationale:
We investigated the nature of ictal apnoeas in a rat model of temporal lobe epilepsy first reported at AES 2022. The relationship between seizures and respiratory malfunction may shed light on mechanisms for SUDEP.
Methods:
Fifteen adult male Wistar rats received injection of tetanus toxin into one ventral hippocampus (List Biological Inc, 25 ng in 11, 75 ng in four compensating for reduced toxicity). Five control rats received saline injections. During the same aseptic operation under anaesthesia, we implanted: intranasal thermocouple, electrodes in ipsilateral dorsal hippocampus and/or contralateral neocortex, ECG leads (11 rats), and EMG leads (four rats) intra-abdominally (for diaphragm)1 and subcutaneously (dorsal rostrolumbar). All sensors connected to a socket cemented to the skull. After recovery from surgery, continuous video-EEG recordings were made through a bespoke preamplifier (Digitimer Ltd), wires and counterbalanced slip rings, and digitized by a 1401 signal acquisition system running SPIKE2 (CED Ltd).
Results:
Ictal apnoeas occurred during spontaneous seizures with secondary generalization. They lasted 9.6±5.07s (mean±SD) and occurred in 315 of a total of 631 stage-5 seizures in toxin-injected rats. We excluded apnoeas being obstructive, because they were not associated with large phasic EMG signals on high-pass filtered ECG and ECoG in 10 rats with the necessary recordings.2 Instead, a large tonic high-frequency signal superimposed on ECG and ECoG was broadly associated with apnoeas (Fig. 1). These HF signals were associated with tonic activity in diaphragm leads (as reported for mice1). However, overlap of apnoeas and tonic EMGs varied considerably, including some with no overlap at all. To date, 7 of 28 apnoeas did not overlap at all with the large tonic EMG; the overall sample differed from full overlap (one-sample Wilcoxon Signed Rank Test, P< 0.001). Similar EMG discharges occurred when rats reared during normal interictal behaviour, simultaneously recorded on a dorsal EMG lead. We conclude the ictal tonic EMG is associated with the rearing phase of these seizures rather than specifically with apnoea. Analysis of apnoeas not overlapping with large tonic EMG revealed a signal smaller (measured as root mean square amplitude, over 20 ms) than the rhythmic breathing preceding the apnoea.