Abstracts

Rationale: TBI and its residuals are major health problems. Genetic factors are known to influence outcome after TBI. Prior research utilizing complementary rat strains bred for increased or decreased rates of perforant path kindling demonstrated differences in sequelae of TBI. The goal of this study is to examine the effects of genetic background on electrophysiologic activity in acute TBI.Methods: Perforant path kindling susceptible (PPKS) and perforant path kindling resistant (PPKR) rats bred from Sprague-Dawley rats were selected for fast or slow perforant path kindling. Controlled cortical impact (CCI) under urethane anesthesia was induced over the right temporo-parietal cortex to produce a moderate-to-severe TBI. Electrographic activity was recorded continuously from epidural electrodes over the left and right hemispheres, beginning 5 min pre-CCI and continuing for 20 min post-CCI. Power within delta, theta, alpha, and beta frequency bands was compared across strains and before and after the CCI. Statistical analysis utilized ANOVA, Bonferroni post-hoc tests, and t-tests with a threshold for significance of p <0.05.Results: Prior to CCI, no differences were found between the two strains or the hemispheres. Following CCI, electrographic activity within the delta band increased over the right (injured) hemisphere in the PPKS rats as compared to prior to CCI (pre-CCI relative delta 38%, post-CCI 55%) and following the CCI as compared to the left (uninjured) hemisphere (left 39%, right 55%). In PPKR rats no changes in relative band power were noted acutely following CCI, although absolute power decreases over the injured hemisphere (pre-CCI 31 sqrt(μV)/Hz, post-CCI 16 sqrt(μV)/Hz). Relative alpha power decreases over the injured hemisphere following CCI in both PPKS rats (pre-CCI 15%, post-CCI 6%) and PPKR rats (pre-CCI 18%, post-CCI 14%), although the PPKS demonstrate a greater reduction that PPKR rats (PPKS 40% of pre-CCI, PPKR 76%). Electrographic activity within the beta band decreased over the injured hemisphere in the PPKS rats as compared to prior to injury (pre-CCI 26%, post-CCI 9.6%) and following the CCI as compared to the uninjured hemisphere (left 24%, right 9.6%).Conclusions: The strain-specific differences described demonstrate that genetic pressures influencing the rate of kindling also influence electrophysiologic activity in the setting of acute TBI. As significant differences exist between the strains in fear context learning after TBI, and the differences in electrophysiologic activity immediately following TBI may be associated with the later behavioral deficits. The appearance of electrographic changes immediately following TBI also suggests electrographic biomarkers of sequelae of TBI may exist early in the course of these disorders. Furthermore, in these strains selected for susceptibility or resistance to epileptogenesis in the kindling model, differences in electrophysiologic activity in the setting of acute TBI may presage differences in other sequelae such as post-traumatic epilepsy. This study was supported by the Susan S. Spencer Clinical Research Training Fellowship.