Expression of c- fos, junB, c- jun, MKP-1 AND hsp72 following traumatic neocortical lesions in rats—relation to spreading depression

Abstract

The effects of a traumatic neocortical lesion on c- fos, junB, c- jun, MKP-1 and hsp72 expression were examined by in situ hybridization and immunocytochemistry 1–6 h following transcranial cold injury. The direct current potential was recorded in the injury-remote cortex to evaluate the role of transient direct current shifts, i.e. spreading depressions, in gene expression. In 14 out of 21 injured rats, spreading depression-like depolarizations of the direct current potential were noticed, which were accompanied by a transient decrease in electroencephalographic activity and increase in laser Doppler flow. In seven injured animals, no spontaneous direct current deflections were seen. In animals without spreading depressions, only a short-lasting response of c- fos, junB, c- jun and MKP-1 messenger RNAs as well as c-Fos protein was bilaterally found in the piriform cortex, and—with ipsilateral dominance—the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injured animals with spreading depressions however, a strong elevation was seen in layers II–IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted over as long as 6 h. Messenger RNA levels for c- fos, junB and MKP-1 were closely related to the time interval between the last direct current deflection and the end of experiment. Levels were highest shortly after transient direct current shifts, and decreased thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c- fos, junB and MKP-1 messenger RNAs, respectively. In 6 h animals with spreading depressions, hsp72 messenger RNA was slightly elevated in layer II of the injury-remote cortex, but Hsp72 was not increased. The present results demonstrate that spreading depression is the most prominent factor influencing the trauma-related gene response in the lesion-remote cortical tissue.