Challenging the autonomous nervous system: Comparison of vagus nerve activity during PTZ-induced seizures and heart rate alteration

Details

Supervisors

El Tahry, Riëm

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Epilepsy is a neurological disease that affects more than 50 million people worldwide, with one-third of patients not responding to anti-seizure medication. These refractory patients are referred to surgery or neuromodulation treatments such as vagus nerve stimulation (VNS). The VNS consists of placing an electrode around the vagus nerve at the cervical level and a stimulator under the collarbone to stimulate the vagus nerve. However, one-third of the patients are non-responders (<50% seizure reduction). Therefore, research has proved that stimulation at the beginning of a seizure improves response rate. We believe seizure detection based on vagus nerve electroneurogram (VENG) would be more sensitive and specific than the detection based on heart rate changes as the vagus nerve relay information from multiple organs as the respiration rate changes, blood pressure variation, etc. Previous acute studies in our laboratory confirm autonomic changes during the induced Pentylenetetrazol (PTZ) seizure, such as cardiac changes leading to increased vagus nerve activity (Stumpp et al., 2021). Therefore, this project aimed to compare changes in vagus nerve activity during heart rate alteration conditions. The experiment conditions were during pharmacological heart alterations induced by epinephrine (EPI) and tonic-clonic (TC) seizures induced after an infusion of PTZ. Therefore, the hypothesis is that the vagus nerve activity will be greater during TC seizures than during a simple change in heart rate since this increase is not the only change in the autonomic nervous system during seizures. For this purpose, we performed acute recording on 8 Wistar rats 270-390g in two different infusion conditions in the lateral tail vein (4 PTZ and 4 EPI). All animals were implanted with epidural electrodes to record the electroencephalogram (EEG), subcutaneous tungsten needle electrodes to record the electrocardiogram (ECG), and a tripolar cuff electrode around the left cervical vagus nerve to record VENG. In the PTZ-infused group, we observed two rats with an increase of heart rate by 4.2 % and 22.63% during the TC stage compared to the baseline. The two last rats had a decrease in heart rate of 3.46% and 6.06%. All four PTZ rats had a steep increase of the VENG during the seizure of 6 ± 1.87-fold compared to baseline. In the EPI-infused group, we observed two decreased heart rates by 10.99% and 1.14% and two increased heart rates by 16% and 1%. For the VENG of the EPI rats, we observed no increase in the VENG during EPI infusion. Consistent with our hypothesis, we obtained a greater increase in VENG during TC seizures than in EPI-infused animals. However, we expected more remarkable changes in heart rate in both groups. Therefore, the EPI infusion protocol will be improved to observe a better change in heart in the future.