Abstracts

Rationale: Sleep disturbances are common and persistent symptoms after traumatic brain injury, which can significantly complicate recovery. In epilepsy, some types of seizure occur primarily during sleep and can be exacerbated by sleep deprivation. However, the relationship between sleep disturbances following brain trauma and development of post-traumatic epilepsy remains poorly understood.

Methods: We developed a large animal model of post-traumatic epileptogenesis, whereby miniature Yucatan pigs were injured at 6 months of age via controlled-cortical impact (CCI) injury. At 5 days post-injury, animals were implanted with wireless EEG system containing a 32-channel hippocampal depth electrode, a 24-channel cortical grid, and 4 bilaterally placed ECoG screws. Chronically implanted pigs were video EEG monitored following brain injury in home cages up to 9 months post-injury. Changes in neurophysiological signals were analyzed for epileptogenesis and sleep disturbances starting at 5 days post sham or CCI injury and up to end points of the study.

Results: Over time, a subset of the CCI-injured (n = 4) but not sham (n = 3) animals presented with epileptiform activity (spikes, bursts, and slow wave discharges) and subsequently developed seizures. 1) Examination of the neuronal properties in hippocampus revealed that at 5 days post-CCI, hippocampal CA1 pyramidal cells had significantly altered firing rates (sham = 3.4 ± 0.8 Hz vs. CCI = 1.554 ± 0.2 Hz, mean ± SEM, p < 0.01) and burstiness (sham = 449 ± 18 µsec vs. CCI = 392 ± 9 µsec, mean ± SEM, p < 0.01), while the electrophysiological properties of hippocampal CA1 interneurons remained unchanged. While there were no changes in the electrophysiological properties of neurons in the cortex at this time point, the number of interneurons detected in the injured cortex were significantly decreased (sham = 8.5 ± 1.5, mean ± SEM vs. CCI = 2.3 ± 0.3, mean ± SEM, p < 0.01). 2) Sleep duration in CCI-injured animals was significantly decreased (sham = 13.8 ± 0.2 vs. CCI = 12.4 ± 0.3 hours, p < 0.01) up to 5 months post-injury. In addition, CCI-injured animals had significantly fragmented sleep, which was frequently interrupted by brief in duration awake periods (sham = 2.6 ± 0.2 vs. CCI = 4.9 ± 0.4 times/NREM1, p < 0.001). Also, CCI-injured animals had a significant increase in delta oscillation (0.5-4 Hz) detected on ipsilateral (sham = 11 ± 2 vs. CCI = 18 ± 01 %, p < 0.01) and contralateral (sham = 12 ± 2 vs. CCI = 18 ± 1 %, p < 0.01) ECoG screws up to 5 months post-CCI.