Robust, long-term video EEG monitoring in a porcine model of post-traumatic epilepsy

Abstract

To date, post-traumatic epilepsy (PTE) research in large animal models has been limited. Recent advances in neocortical microscopy have made possible new insights into neocortical PTE. However, it is very difficult to engender convincing neocortical PTE in rodents. Thus, large animal models that develop neocortical PTE may provide useful insights that also can be more comparable to human patients. Because gyrencephalic species have prolonged latent periods, long-term video EEG recording is required. Here, we report a fully subcutaneous EEG implant with synchronized video in freely ambulatory swine for up to 14 months during epileptogenesis following bilateral cortical impact injuries or sham surgery The advantages of this system include the availability of a commercially available system that is simple to install, a low failure rate after surgery for EEG implantation, radiotelemetry that enables continuous monitoring of freely ambulating animals, excellent synchronization to video to EEG, and a robust signal to noise ratio. The disadvantages of this system in this species and age are the accretion of skull bone which entirely embedded a subset of skull screws and EEG electrodes, and the inability to rearrange the EEG electrode array. These disadvantages may be overcome by splicing a subdural electrode strip to the electrode leads so that skull growth is less likely to interfere with long-term signal capture and by placing two implants for a more extensive montage. This commercially available system in this bilateral cortical impact swine model may be useful to a wide range of investigators studying epileptogenesis in PTE.

A team science approach for the preclinical and clinical characterization and biomarker development for post‐traumatic epilepsy

“…The Massachusetts General Hospital team developed a dual‐contusion model of PTE in Yucatan minipigs, with initial data suggesting an increase in epileptiform discharges around the time of onset of convulsions 17,18 . Preliminary data from this model also suggests approximately 50% incidence of PTE over several months and explored a working sequence of peri‐ictal behaviors of PTE in this large animal model 19 .…”

“…Preliminary data from this model also suggests approximately 50% incidence of PTE over several months and explored a working sequence of peri‐ictal behaviors of PTE in this large animal model 19 . Specifically, the team described the pattern of simple and complex spikes, spike trains and convulsions, accompanied by disturbed sleep patterns in the minipigs 18 . In addition, the team developed in vivo cortical chloride imaging to test the hypothesis that damage to the extracellular matrix may play a role in the development of PTE following TBI and that this can be evidenced by changes in extracellular and intracellular concentrations of chloride levels.…”

2-Photon imaging of fluorescent proteins in living swine

“…Two swine (18 months of age, 76 -84 kg) had received cortical impact 12 months prior to imaging. One pig had developed post-traumatic epilepsy; both were imaged to determine Clo 10 . The cranial imaging windows were observed in 2 pigs 3.5 month after installation.…”

“…The PDMS iteration in this case had a silicone ring/ "hat" attached to line the burr hole and more difficult to place. There was a large space-filling hemorrhage under the PDMS membrane in an animal that had previously placed skull screws for EEG 19 perhaps limiting movement and accommodation of the brain to the hematoma. Placing the PDMS membrane does present a risk of laceration of cortical veins and re-bleeding after skin closure.…”