Abstracts

Rationale: Controlled-cortical impact (CCI) has been widely used as a model of traumatic brain injury (TBI), and several previous studies have used CCI in rodents as a possible model of post-traumatic epilepsy (PTE). Although previous studies have found evidence of 'late' spontaneous recurrent seizures (SRSs) after CCI (Hunt et al., Exp Neurol 2009; Statler et al., Epilepsy Res 2009, Bolkvadz & Pitkanen, J Neurotrauma 2012: Kelly et al, Epilepsy Res 2015), the percent of animals with clear SRSs and the SRS frequency were quite low, at least compared to models based on status epilepticus. These experiments aimed to assess PTE with long-term monitoring using a rat model of CCI.  Methods: Male Sprague-Dawley rats (n=20) were recorded with 1, 2 or 3 channels for 1-8 months using either EpochTM or DSI transmitters for wireless recordings from sites ipsilateral and contralateral to the CCI-induced injury. Brains of the animals were impacted with a 6-mm impactor at 5 m/s 2.8 mm deep with a dwell time of 1 ms over the caudal part of the animal's cortex. The impact resulted in an injury with severe damage to the cortex, hippocampus and thalamus of the brain. Another n=19 rats served as sham controls. Many rats (n=34) received a Neurological Severity Score based on their behavior. Long-term, continuous video-EEG recordings were obtained for up to 8 months after the CCI-injury. SRSs and spike-wave discharges (SWDs) were analyzed with various seizure/spike-detection algorithms and manually with direct observation. Results: The CCI-injured rats sustained severe cortical and subcortical damage, based on gross anatomic observations and Neurological Severity Scores. To examine effects of injury on the EEG recorded acutely and sub-acutely, several rats were selected from a cohort and analyzed. The CCI-treated rats (n=8) showed evidence of 'slowing' that recovered over several weeks after injury. The slowing was not present in sham controls (n=8). Some CCI and sham-control rats (n= 3 CCI, n=2 shams) had 'early' seizures within the first week after injury. Nearly all sham and CCI rats showed SWDs, with no apparent difference in their properties between groups, These events increased with age in both groups. 'Late' SRSs were not detected in any of the rats, even with continuous video-EEG monitoring for many months.  Conclusions: These data suggest that even with relatively severe CCI - based on behavioral studies, MRI, and gross anatomic observations, rats with “late” SRSs are relatively rare and/or their frequency is low.  Electrographic “slowing” and some cases of “early” seizures occur in this model, in spite of a lack of “late” SRSs. Because SWDs were routinely found in both sham-control and CCI-injured rats, they seem to have no relationship to TBI/PTE. Further studies are necessary to insure that these data do not represent a “false negative,” but our results – consistent with previous studies – suggest that although PTE can occur after CCI, it is relatively infrequent, at least under the conditions used here. Other approaches are under investigation to determine if they will increase the “late” of SRSs (i.e., epilepsy) found in the CCI model.  Funding: Funded by grants from NINDS (NS NS086364) and CDMRP EP150033