Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury

Damage to the frontal cortex and to the hippocampus, both in terms of cell loss and neuronal dysfunction, is thought to underlie many of the neurological and behavioural consequences of traumatic brain injury (TBI). Several studies have indicated that the hippocampus is particularly susceptible to central nervous system insults, whereas the frontal cortex possesses relatively higher capacities for regeneration and plasticity. It has been postulated that dissimilarities in the gene expression profiles in these structures, both in the normal and the postinjury states, may underlie these differences. In order to explore this issue, mRNA samples taken from the frontal cortex and the hippocampus of uninjured animals were subjected to high-density microarray analysis. The analysis indicated that the mRNA levels of 65 genes were differentially expressed between these two brain regions. Among these, genes involved in intracellular signalling, neurotransmitter release, and genes encoding for channels and receptors were identified. Samples taken from animals injured using controlled cortical impact (a model of TBI) showed altered mRNA levels for 341 frontal cortex genes 24 h following injury. These genes can be broadly classified into one of 12 functional classes: cell cycle, metabolism, reactive oxygen metabolism, inflammation, receptors, channels and transporters, signal transduction, cytoskeleton, membrane proteins, neuropeptides, growth factors, and proteins involved in transcription/translation. The expression profile of these genes is compared to the expression profile of 241 genes in the hippocampus 24 h following cortical impact injury as previously reported by our laboratory. In addition to genes previously reported in the literature, this study found several genes that have not been associated with TBI. The functional implications of changes in the expression of some of these genes are discussed.