Swine model for translational research of invasive intracranial monitoring

Abstract

Summary Focal cortical epilepsy is currently most effectively studied in humans. However, improvement in cortical monitoring and investigational device development is limited by lack of an animal model mimicking human acute focal cortical epileptiform activity under epilepsy surgery conditions. Therefore, we assessed the swine model for translational epilepsy research. Swine were used due to their cost effectiveness, convoluted cortex, and comparative anatomy similar to humans. Focal subcortical injection of benzyl-penicillin produced clinical seizures correlating with epileptiform activity demonstrating temporal and spatial progression. Swine were evaluated under 5 different anesthesia regimens. Of the 5 regimens, conditions similar to human intraoperative anesthesia, including continuous fentanyl with low dose isoflorane, was the most effective for eliciting complex, epileptiform activity after benzyl-penicillin injection. The most complex epileptiform activity (spikes, and high frequency activity) was then repeated reliably in 9 animals, utilizing 14 swine total. There were 20.1 ± 10.8 (95% CI: 11.8–28.4) epileptiform events with greater than 3.5 hertz activity occurring per animal. Average duration of each event was 46.3 ± 15.6 (95% CI: 44.0 to 48.6) seconds, ranging from 20 to 100 seconds. In conclusion, the acute swine model of focal cortical epilepsy surgery provides an animal model mimicking human surgical conditions with a large brain, gyrated cortex, and is relatively cheap among animal models. Therefore, we feel this model provides a valuable, reliable, and novel platform for translational studies of implantable hardware for intracranial monitoring.

Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

“…The swine model was chosen because the large brain volume (pig brain:~160g) is comparable to that of the non-human primate (rhesus monkey brain:~100g) (Hardman et al, 2002; Shon et al, 2010), and with a gyrencephalic cortex, more closely represents human brain anatomy than do the brains of small animal models, such as rodents (Pour-El, 2006; Shon et al, 2010; Van Gompel et al, 2011; Wakeman et al, 2006). We took a novel approach using a high-resolution 3-dimensional pig brain atlas (Saikali et al, 2010), which allowed us to normalize the functional activation map and to apply general linear modeling in each subject group.…”

Nucleus Accumbens Deep Brain Stimulation Results in Insula and Prefrontal Activation: A Large Animal fMRI Study

“…Indeed, being similar in size and organization to the brain of the non-human primate [39], [40] the gyrencephalic swine brain, in contrast with the brain of small animals, is more closely representative of the human brain [39], [40], [41], [42]. Specifically, the mean± standard error of the mean (SEM) distance between the anterior commissure and posterior commissure (AC-PC) length for pigs in this study was 12.94±0.30 mm as compared to the 28.3±0.2 mm human AC-PC length that has been reported in the literature.…”

Development of a Model of Hemispheric Hypodensity (“Big Black Brain”)

“…38,39 Anesthetic protocols using fentanyl alone or in combination of dexmedetomidine failed to induce adequate sedation as previously described in piglets. 31,40 It is possible that these protocols failed to work in our hands because we induce neuromuscular blockade only after morphine and dexmedetomidine successfully sedated animals to ensure that sedation is adequate during paralysis. Fentanyl is a l-opioid receptor agonist that works well in humans, but we found that morphine, which binds to multiple opioid receptors, worked better as a sedative in piglets, with a dose previously used for anesthesia in elective open heart surgery.…”

“…After the surgery to create the injuries, piglets were weaned off isoflurane and a bolus of fentanyl (60-100 lg/kg) followed by a continuous infusion (30-100 lg/kg/h) that was previously reported to induce anesthesia failed to produce adequate sedation alone 40 or in combination with dexmedetomidine (10-30 lg/kg/h). 31 Additional boluses of fentanyl (20 lg/kg) failed to prevent movement, indicating inadequate levels of anesthesia.…”