The rodent brain offers extraordinary access to studying detailed physiology of the epileptic brain. However, some important differences exist between rodent brains and human brains. Most notably these include size, white matter-to-gray matter ratio, and the presence of folds (gyrencephalic vs lissencephalic).
There are also important differences in the brains response to injury. In rodent models of post-traumatic epilepsy, cortical impact leads to a disappearance of the injured cortex and emergence of seizure activity in the underlying hippocampus. In pigs (and humans) brain injury leads to swelling of the injured tissue and, most commonly, emergence of a cortical seizure focus.
We hypothesize that injury-induced changes in the composition of the brain’s extracellular matrix alter excitability of the injured tissue. To test the hypothesis, in a collaboration between the Pediatric Epilepsy Research Group and the Brain Trauma Lab, we developed a porcine model of post-traumatic epilepsy where bilateral cortical impact leads to epilepsy with a probability of approximately 50%. To answer fundamental questions about changes in intra and extracellular chloride and neuronal network excitability, we also developed techniques to virally transduce fluorescent protein-based biosensors and perform longitudinal two-photon imaging at the site of injury.
