Abstracts

Rationale:  Fluid percussion injury (FPI) is a leading model of human closed-head injury and has been used to model post-traumatic epilepsy (PTE) in rats. Several laboratories have described “epileptiform electrocorticography events” (EEEs) in the ECoG of rats following FPI that they conclude reflect non-convulsive seizures (D’Ambrosio, R, et al., Brain, 2009). While EEEs appear very similar to spike-wave discharges (SWDs) seen in uninjured control rats and in rat models of absence epilepsy, it is claimed that they may be distinguished by their focal (as opposed to bilaterally synchronous) onset on the side of injury (Reid, AY, et al., Epilepsia, 2016). We hypothesized that if focal EEEs uniquely reflect PTE, and not normal SWDs or those associated with absence epilepsy, they should be insensitive to the anti-absence drug ethosuximide (ETX), which suppresses the later SWD events in rats. Methods: Thirty-six 2-month-old male Wistar rats were instrumented with bilateral parietal screw electrodes following severe (3 atm), parietal FPI (n=28), or sham surgery (n=8). Chronic video/ECoG recording was performed for up to 9 months post-injury and a support vector machine was trained to detect SWDs. At approximately 9 months, SWD bursts were also visually quantified for 1 day prior to, during, and following ETX injection. Results: Histological data indicated that both sham and FPI-injured rats sustained cortical damage; however, far more damage was seen in the FPI rats. Neither FPI-injured nor sham rats displayed any spontaneous recurrent seizures despite the severity of injury. All rats – FPI-injured and controls – displayed SWD bursts that became more frequent with age. While most of the SWDs had bilaterally synchronous onsets, approximately 16% of the bursts detected in both groups began focally (with typical latencies of 0.5-1.0 s), ipsilateral to the injury. In sham and FPI-injured rats, ETX profoundly suppressed SWDs of both focal and bilaterally synchronous onset. Conclusions: ETX suppression of focal as well as bilaterally synchronous onset SWDs in the FPI model suggests that both burst types share the same thalamocortical circuits and may rely on T-type calcium channels known to be ETX sensitive. As such, neither focal- nor synchronous-onset SWDs in the FPI model were distinct from those in sham-controls or those reported in rat models of absence epilepsy, which also show the same frequency, waveform morphology, and burst durations. However, when focal SWDs did occur, they were consistently on the side of the craniectomy and injury. Thus, while not likely reflecting PTE or seizures, these events may represent an aberration of normal SWD rhythms possibly induced by injury-related alterations in cortical excitability. Funding: Funded by CURE 411446 and CDMRP EP150033