Abstracts

Rationale: Post-traumatic epilepsy (PTE) develops in ~5-50% of people who sustain traumatic brain injury (TBI). There is a need for good models of PTE to study mechanisms of epileptogenesis and potential interventions. However, there is a paucity of reports of specific seizure frequency, duration, and time to first seizure after experimental TBI. We report here these characteristics after controlled cortical impact (CCI) in rats observed as part of a study of EEG dynamics as predictors of PTE after TBI.Methods: Thirty-six adult male (300 gm) Sprague-Dawley rats underwent a 6 mm diameter right parietal craniotomy under ketamine/dexmedetomidine anesthesia. Then, using a pneumatically controlled cortical impact device, a 6 mm diameter piston was made to strike the surface of the brain at a velocity of 5.5 meters per second and to penetrate 3 mm into the cortical surface of the brain for a total duration of 55 msec. Immediately following CCI four cortical electrodes, two hippocampal electrodes, and two centromedial thalamic nuclei electrodes were implanted. Starting 10 days after surgery, rats were monitored continuously for 16 weeks using an Xltek EEG recording machine to determine the time of onset, frequency, and duration of spontaneous seizures, as detected by visual inspection of the EEG. At the end of the observation period, histology was performed to verify the location of the lesion and recording electrodes. A subset of nine rats was trained in a Morris Water Maze (MWM) prior to CCI/electrode implantation and then tested again at the completion of the 16 week monitoring period.Results: Three rats died prior to starting EEG monitoring. Thirty-three rats were recorded up to 16 weeks. Of these, 21 (63.6%) developed epilepsy (two or more seizures), but only 19 completed 16 weeks of recording because of loss of recording head caps, usually from violent seizures. Seizures typically were complex partial seizures with behavioral arrest, chewing movements, and whisker twitching accompanied initially by low voltage beta activity which increased in amplitude and slowed in frequency. The mean time to the 1st seizure was 46 days after CCI (median 46 days, range 11-87 days) and the weekly frequency of seizures for epileptic rats was 1.16 (range 0.2-4.0). The mean duration of electrographic seizures was 2 min 10 sec (range 6 sec to 8 min 17 sec). Performance in the MWM was significantly impaired when rats were tested 16 weeks after CCI. The mean time to find the platform on the 4th pre-CCI training day was 10.6 8.5 sec; the mean time to the platform on the 1st 16 week post-CCI test day was 23.2 20.7 sec. Hematoxylin and eosin staining showed significant loss of brain tissue in the impacted area.Conclusions: The CCI model of TBI can be used to reliably and efficiently induce PTE, as manifested by discrete behavioral and electrographic seizures and also cognitive deficits in the MWM, and thus can serve as a good model for the study of post-TBI epileptogenesis and its mechanisms and treatment. Support: DOD grant PT090712/W81XWH-11-1-0283 and ABRC grant 1121