Expression of c-jun, hsp72 and gfap following repeated unilateral common carotid artery occlusion in gerbils-correlates of delayed ischemic injury.

The relationship between gene responses and cumulative ischemic damage, as induced by two 10 min episodes of unilateral common carotid artery (CCA) occlusion separated by 5 h, was examined by in situ hybridization histochemistry and terminal transferase biotinylated-dUTP nick end labeling (TUNEL) in the gerbil brain. Intense cell death was noticed starting from 5 h after the second ischemic insult, reaching maximum levels in the nucleus caudate-putamen and thalamus at 12-24 h, but in the cortex and hippocampus at 2 days post-ischemia. Although tissue damage developed gradually, the region of progressive infarction could be delineated as an area deficient in gfap mRNA starting from 12 h, more apparent 24 h after repeated ischemic insults. Hsp72 mRNA was strongly increased in the cortex, caudate-putamen, ventrolateral thalamus, CA1-CA4 fields and dentate gyrus in the early stages, i.e., 15 min-5 h post-ischemia. C-jun mRNA was also elevated in these structures except for the CA1 field, where mRNA levels remained low. In the caudate-putamen and thalamus, where DNA fragmentation occurred rapidly, c-jun and hsp72 mRNAs declined to almost basal levels within 12 h after repeated ischemia, whereas in the other structures, c-jun and hsp72 mRNAs decreased in a more delayed fashion by 24-48 h. The close association between the c-jun and hsp72 mRNA decline and the onset of injury may reflect a more general disruption of the transcription process probably as the consequence of secondary metabolic deterioration. The dissociation between c-jun and hsp72 mRNA expression in the CA1 field may indicate severe ischemic injury, surpassing the range of tissue salvage.