Acute and Subacute Differential Gene Expression in Rat Midbrain Following Blast Exposure Compared to Mechanical Brain Trauma

In this study, we employed two models of traumatic brain injury (TBI) in rats: head-directed blast overpressure exposure (OBI) and mechanical controlled cortical impact (CCI). Two groups of animals served as controls: naïve rats and rats exposed to blast noise. A genomics neurosystems biology approach was used to analyze differential gene expression between experimental groups. Midbrain RNA was isolated 24 hours (acute) and 7 days (subacute) after traumatic insult, probed with Affymetrix array containing 31,100 gene sequences, and quantified by Agilent Technologies. Differentially expressed genes were grouped into functional clusters and the significance of gene expression changes at 24 h and 7 days was further assessed using parametric and nonparametric t- test with Welch correction. Then, gene interactions in pathological pathways following blast exposures vs. mechanical impact were created and analysed using neurosystems biology tools. According to ANOVA (p<0.05), there was a significant difference in expression of 994 genes within blast exposure groups (vs. control) and in 1532 genes within CCI group (vs. control) with an overall overlap of 579 genes. Parametric and nonparametric t-tests revealed significant differences in temporal profile of changes in various genes at 24 hours vs. 7 days in blast exposed animals compared to CCI. Specifically, genes involved in neural development and repair, such as ROBO1 and NEDD4 were up-regulated in CCI, while they were shown to be down-regulated following blast exposure. These results demonstrate several differences as well as overlaps in the expression of genes between the two brain insults. This will help to reveal specific molecular signatures of each brain insult and assist in developing diagnostics of chronic posttraumatic encephalopathy.