Abstracts

Rationale: Post-traumatic epilepsy (PTE) in humans is a heterogeneous neurological disorder, varying in severity and syndrome. Several factors may underlie this heterogeneity, including age at time of injury, genetic background, as well as location, type and severity of the injury. Indeed, fluid percussion injury (FPI) in the rat is found to induce different seizure frequencies and PTE syndromes in different laboratories. Thus, to begin clarifying the factors responsible for the variability of PTE in humans, and begin standardizing the FPI model of PTE, we investigated the effects of three different injury locations and two different degrees of severity. Methods: 30 day-old male Sprague-Dawley rats received either moderate (2 atm) or severe (3.5 atm) FPI. Percussions were delivered to either frontal parietal (fpFPI), parietal (pFPI), or parietal occipital (poFPI) areas. One week after injury, 5 epidural electrodes were implanted for chronic video-electrocorticography (ECoG). At least 48 hours of video-ECoG data were acquired at 3 time points (2-3, 8-9, 17-19 weeks after injury) from each animal of the 6 different experimental groups. Results: More severe trauma (3.5 atm) resulted in a higher probability of developing epilepsy for all locations of injury investigated. At 2-3 weeks after injury, the probability of developing epilepsy was ~0.43 following moderate fpFPI and ~0.75 following severe fpFPI. Similar results were obtained after pFPI (~0.43 for injury at 2 atm and ~0.67 for injury at 3.5 atm), and poFPI (~0.45 and ~0.60 for moderate and severe injury respectively). No sham-injured animals developed epilepsy within 18 weeks of observation (n=10). Seizure frequency was higher when severe trauma was applied. At 2-3 weeks after fpFPI, the mean seizure frequency was 3.26±1.17 events/hour for rats injured at 3.5 atm (n=26), and only 0.21±0.18 events/hour for those injured at 2 atm (n=7). pFPI rats presented with a mean seizure frequency of 0.15±0.06 events/hour (n=12) when injured at 3.5 atm, and 0.03±0.02 events/hour (n=7) when the milder pressure was applied. The mean seizure frequencies of poFPI rats were 0.19±0.06 events/hour (n=15) at 3.5 atm pressure pulse and 0.16±0.08 events/hour (n=11) at 2 atm pressure pulse. At 2-3 weeks post injury, more than 90% of events presenting with focal neocortical onset originated from the frontal-parietal cortex even when trauma was applied in parietal or parietal occipital neocortex. Conclusions: Similarly to human PTE, the severity of FPI correlates with a higher probability of developing epilepsy in the rat. In addition, seizure frequency is higher with higher mechanical severity of FPI. Injury severity being equal, the frontal neocortex of the rat is more epileptogenic than the parietal and parietal occipital ones. Thus, FPI delivered to the frontal cortex is ideal for experimental and translational studies of PTE which require seizure frequencies adequate to power studies. Supported by NIH NS053928 (RD).