The objective of this study was to define the time- and brain-area-related distribution of c-fos expression in the brain during the first 24 h following a closed head injury in rats. In the control groups (n=32), only a few c-fos positive nuclei were observed in the brain and the c-fos staining did not change during the next 24 h. In the closed head injury group c-fos-positive cells were rare in the brain regions during the first 30 min. During the next 2 h, the number of c-fos-positive cells increased rapidly in the basal ganglions, the ventricular ependyma cells the corticospinal tract, the area postrema, the cerebral neocortex, and the corpus callosum. The increase was highest in the corpus callosum (317±44.5 mm−2), in the thalamic reticular nucleus (474.8±49.2 mm−2), in the dentate hilus (1090±187 mm−2) and in the cerebral neocortex (992±93 mm−2). Thereafter, the elevated c-fos expression gradually decreased and at 6 h post-closed head injury no significant differences were observed between the controls and the trauma group. We conclude that a closed head injury induces a large, transient increase of c-fos expression in the brain. Since the observed time course and regional differences in c-fos expression are in good agreement with the cognitive and memory deficits observed after human TBI it can be utilized in further investigations, especially to test the effects of various forms of pharmacological or cellular therapy.

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