Abstracts

Rationale: Spike-and-wave discharge (SWD) has long been recognized in inbred rat strains as the electrographic hallmark of non-convulsive episodes that mimic absence seizures in humans. Similar patterns have also been reported in the electrocorticogram (ECoG) of rats undergoing lateral fluid percussion injury (LFPI), a leading model of post-traumatic epilepsy, and thought to reflect early signs of epileptogenesis preceding spontaneous convulsive seizures. However, it has been recently reported that SWD are observed in uninjured Sprague-Dawley rats used as controls in these and other models of acquired epilepsy. The presence of SWD in control rats raises the possibility of confounds in the interpretation of results from acquired epilepsy models if they are thought to also reflect epileptogenesis. Methods: The present study quantified features of SWD episodes throughout the lifetime of normal "control" rats with the objective of distinguishing normal brain activity from that heralding the development of non-convulsive and convulsive seizures. These results were compared to the same timeline in brain-injured rats receiving moderate to severe LFPI. A support vector machine was trained on the fully developed SWD of each rat and used to detect and quantify subsequent episodes. Results: A majority (approximately 80%) of older (8-12 mo) control rats displayed large-amplitude and frequent SWD bouts at parietal recording sites. These events occurred in bursts of 1-30 sec duration with a typical repetition frequency of approximately 1-4/hr. Earlier recordings in the same rats also revealed clear SWD at 3-6 mo age that were of shorter duration and less frequent, and occasional "larval" SWD detected as early as 1 mo of age. All features of SWD quantified for control rats were evident in LFPI animals, including a marked increase in the frequency of occurrence, duration and amplitude with age. Initial analysis indicated that the prevalence of SWD at earlier time-points (3-6 mo) close to the time of injury may be greater in LFPI rats, but this was too variable to reach significance. Conclusions: These results suggest that the presence, duration, amplitude, and frequency of occurrence of SWD may not unambiguously reflect epileptogenesis in acquired epilepsy with moderate to severe LFPI. However, none of our LFPI rats developed convulsive seizures across 1-12 mo of video/EEG monitoring. Work is underway to examine LFPI animals undergoing more severe impact pressures to determine parameters of SWD that may be uniquely associated with epileptogenesis.