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

Abstract

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.