Expression of c-fos, junB, c-jun, MKP-1 and hsp72 following traumatic neocortical lesions in rats--relation to spreading depression.
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 spreading depressions 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 depolarization 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 heat shock protein 72 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.
Hermann
D M
DM
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
Mies
G
G
Hossmann
K A
KA
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D018797:Cell Cycle Proteins; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D054638:Dual Specificity Phosphatase 1; D004594:Electrophysiology; D015870:Gene Expression / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017078:Laser-Doppler Flowmetry; D008297:Male; D019579:Neocortex / Q000098:blood supply / Q000166:cytology / Q000293:injuries*; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018797:Cell Cycle Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases