OBSERVED RELATIONSHIP BETWEEN SEIZURES AND SPREADING DEPRESSION IN THE TETANUS TOXIN MODEL OF TEMPORAL LOBE EPILEPSY
Open Access
- Author:
- Curay, Carlos
- Millennium Scholars Program:
- Biology (BIOL)
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisor:
- Bruce Gluckman, Thesis Supervisor
- Keywords:
- Seizure
Biology
Spreading Depression
Tetanus
SUDEP - Abstract:
- Spreading Depression (SD) and Seizure dynamics were assumed in older literature to be strongly associated, and early acute (evoked) seizure investigations were accompanied by the emission of SD waves [12]. There has recently been renewed interest in the link between seizure and SD - including theoretical work implicating that these source from a unified set of instabilities [9], and from the hypothesis that Sudden Unexpected Death in Epilepsy is mediated by SD invasion of brainstem [11]. There have been only rare if any observations of spontaneous seizure-associated SD events. We hypothesize this is primarily due to technical/instrumentation limitations. We first observed SD events associated with spontaneous seizures in a murine model of post-cerebral malaria epilepsy [6] with an in-house constructed digital recording system with DC sensitivity, sufficient dynamic range, and non-polarizing electrodes. Here we report that spontaneous SD events occur frequently in the tetanus toxin model of temporal lobe epilepsy. We have extended our system to provide 16 channels of biopotential recording plus head acceleration in rats. We utilized this technology for experimental measurements of cortical activity and hippocampal field potentials. We find that initiation of SD events is linked to the seizure focus and that SD events potentially mediate seizure severity and underlie seizure clusters. These measurements are the first record of spontaneous seizure-related spreading depolarization in an animal model of temporal lobe epilepsy. They provide a platform for mechanistic investigation of seizure-SD dynamics in chronic epilepsy and cases of sudden unexplained death in epilepsy (SUDEP) that may lead to new intervention and treatment approaches.