Expression of c-fos in the hippocampus following mild and moderate fluid percussion brain injury.

Abstract

An oncoprotein mediator of gene expression, c-fos, was evaluated in the central fluid percussion model of traumatic brain injury (TBI). Since hippocampal CA1 neurons are particularly vulnerable to TBI, we hypothesized that TBI may produce pathobiologic changes in CA1, in part, by alterations in gene expression through c-fos. Sprague-Dawley rats were subjected to mild (1.0 atm) or moderate (2.1 atm) fluid percussion TBI or sham injury. At 15 min, 1 h, and 24 h after injury (or sham injury), sections from middorsal hippocampus were immunostained with antibodies to c-fos, and c-fos-positive CA1 neurons were counted. As predicted, c-fos was localized in the nuclei of CA1 pyramidal neurons. However, the intensity of label was not equal over all CA1 neurons. Cells with high-intensity c-fos label were more prevalent after mild TBI. The number of c-fos-labeled CA1 neurons was increased at 15 min after both mild and moderate TBI relative to paired sham controls. Counts of c-fos-positive neurons remained significantly elevated at 1 h postinjury only after mild TBI. By 24 h postinjury, the number of c-fos-positive cells at both injury levels was not different from sham controls. No difference was observed between the number of c-fos-positive cells in naive and sham controls. However, label intensity was slightly less in the naive cases. These results suggest that the pathobiologic changes at early intervals following mild or moderate TBI may involve c-fos alteration of gene expression and that c-fos expression may be differentially regulated as a function of injury level.