Abstracts

Rationale: Traumatic brain injury is one of the largest causes of acquired epilepsy (post-traumatic epilepsy (PTE)). A prominent clinical question has been the relative contribution of diffuse and focal brain injury to the process of epileptogenesis. In order to monitor electrophysiological changes post injury over time, we have developed and successfully implemented a Large Animal Custom Enclosure System (LACES), which consists of a 64-channel wireless recording system combined with a custom 32-channel hippocampal depth probe, a 32-channel cortical grid and other ECoG electrodes. This system allows for 24/7 video monitoring of awake behaving pigs, with alternate days of 24/7 monitoring of the electrophysiological signals. Methods: Electrophysiological changes post traumatic brain injury (TBI) were studied in male Yucatan miniature pigs injured at 6 months of age in the inertial model of diffuse axonal injury (DAI), in the controlled cortical impact (CCI) injury model, or in the combination of both injuries for comparison of the development of epileptogenesis in these injury types. Oscillatory field potentials and single-unit neuronal activity were recorded with laminar silicon probes placed in the pig dorsal hippocampus, while cortical activity was recorded with surface grid electrodes and skull ECoG screws placed in the contralateral hemisphere. Results: At time points up to 5 months, we observed subclinical epileptiform activity in cortex and hippocampus of injured but not sham animals. Preliminary data suggest an interaction between the rotational and contusion injuries when superimposed. These events could be correlated to changes in spectral entropy over time. A post-mortem examination of neuropathology is being performed, with emphasis on the temporal lobe connections. Behavior, along with number and frequency of epileptogenic events will be correlated with the neuropathological outcomes to determine mechanistic underpinnings of PTE. Conclusions: The rotational injury data suggest that diffuse brain injury may induce hippocampal axonal and synaptic dysfunction and changes in hippocampal cellular excitability. The CCI model leads to substantial cortical and axonal pathology that has the potential for inducing seizure activity. Comparison and superimposition of these injuries combined with long-term video-EEG in this large animal model could clarify the contribution of each injury type to post traumatic epileptogenesis.  Funding: DoD ERP CDMRP, W81XWH-16-1-0675