Abstract 221 Critical Care Platform, Monday, 5/3

We are pioneering the study of developmental differences in the response to closed head injury in rats. We have described differences in outcome and physiology following fluid percussion injury (FPI) between immature and mature rats. We are now testing the hypothesis that FPI will lead to specific patterns of immediate early gene (IEG) induction in rats of different ages.

Six 17-day old (P17) and four adult (A) rats were subjected to left lateral FPI. Two P17 and two A rats underwent surgery without FPI (Sham). Surgeries were performed under enflurane anesthesia. Injury severity was graded by the duration of unconsciousness (DOU) defined as the time from injury until the animal responded to a toe pinch. Three P17 rats received mild FPI (DOU: 6-30s). Two P17 rats received moderate FPI (DOU: 45-91s). One P17 and 4 A rats received severe FPI (DOU: 149-820s). One hour after injury, the rats were sacrificed and total RNA was isolated from the left hippocampus. The RNAs were subjected to northern analysis with probes representing a group of IEGs that are induced in neurons by depolarization. The data are presented as fold induction over sham (mean±SD). (Figure)

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cfos has the most robust induction after all levels of injury and the clearest correlation between fold induction and injury severity (mild 3.6±0.5, moderate 5.6±1.0, P17 severe 17.4, A severe 16.5±3.5). NGFI-B induction also correlates with injury severity (mild 1.4±0.2, moderate 1.7±0.3, P17 severe 3.3, A severe 6.0±1.0). KID-2 is somewhat induced by severe FPI in both P17 (1.5) and A (2.3±0.9). NURR1 and KID-1 are induced only in A (3.5±0.3 and 1.7±0.1 respectively). Sec1 and sytIV are not induced 1 hour after FPI. After severe FPI, A rats respond with more robust gene induction than P17 rats. This is interesting as the adults had shorter DOU than the P17 (149-224s versus 820s).

These preliminary data support the hypotheses that IEG induction after FPI is specific to the gene, severity of injury and stage of maturation of the injured animal. We are expanding our study of IEG induction after FPI in rats.

Supported by AR01870, NS30308, NS27544, NS28660.