Abstracts

Rationale: The pathological network alterations that correspond with the development of post-traumatic epilepsy (PTE) are not known. In animal models of PTE, there is evidence that hippocampal hyperexcitability begins shortly after traumatic brain injury (TBI), and may contribute to the subsequent development of post-traumatic seizures. Based on studies using status epilepticus (SE)-induced animal models and surgical patients with epilepsy, results suggest that pathological high frequency oscillations (HFOs; 250-600Hz) reflect basic neuronal disturbances responsible for epileptogenicity, and may also play a role in epileptogenesis. Therefore, it is possible that pathological HFOs are associated with the development of PTE. In order to evaluate this hypothesis, TBI was induced in rats using lateral fluid percussion injury (FPI), a widely used technique that reproduces many features of human TBI that often includes PTE. High frequency depth EEG recordings were carried out to determine whether lateral FPI-induced network alterations support the generation of pathological HFOs, and correspond with the development of PTE. Methods: A craniotomy overlying the left hemisphere was the site for lateral FPI in adult Wistar rats. Bilateral depth electrodes with 1.5mm inter-tip spacing were positioned in hippocampal areas anterior and posterior to site of injury, and recorded wide bandwidth (0.1-3kHz) depth EEG that started immediately after injury. Depth recordings were reviewed for occurrences of pathological HFOs, and analyzed with respect to the appearance of post-traumatic seizures. Results: Depth electrode recordings immediately following brain injury captured multiple, independent seizures in 1 rat that remitted within 48 hours, while no early seizures were detected in the remaining 3 injured rats. Analysis of depth recordings revealed the occurrence of abnormal HFOs primarily in ipsilateral dentate gyrus (peak spectral frequency ≥140Hz) and hippocampus (≥260Hz) that could be detected several hours after injury, but were consistently observed days to weeks following injury in all rats. In some rats, single pulse electrical stimulation evoked hippocampal network responses that consisted of multiple population spike discharges that resembled spontaneous abnormal HFOs. Abnormal HFOs occurred prior to the appearance of late post-traumatic seizures, which were captured in all rats during long-term monitoring at latencies that ranged from 15 to 158 days following injury. Furthermore, abnormal HFOs were associated with the onset of some hippocampal seizures. Conclusions: Results indicate that abnormal HFOs observed in rats immediately after lateral FPI resemble pathological HFOs found in SE-induced chronic animals models and patients with epilepsy. The specificity of pathological HFOs in predicting PTE cannot be determined from these data because all rats in this preliminary study developed PTE . However, pathological HFOs were present in the absence of early seizures, and suggests pathological HFOs may be a more sensitive predictor of PTE than early seizures.