DISTRIBUTIONS OF HEAT-SHOCK PROTEIN (HSP)-70 AND HEAT-SHOCK COGNATE PROTEIN (HSC) 70 MESSENGER-RNAS AFTER TRANSIENT FOCAL ISCHEMIA IN RAT-BRAIN

The distribution of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNA after 30 min of middle cerebral artery (MCA) occlusion was investigated in rat brain by in situ hybridization using cloned cDNA probes selective for the mRNAs. While HSP70 mRNA was hardly present at caudate and dorsal hippocampal levels of the sham brain this mRNA was greatly induced in cells of the MCA territory 1 h after reperfusion. Although the maximum amount of induced HSP70 mRNA in the caudate was much smaller than that in the cortex the maximum induction in the caudate (3 h) preceded that in the cortex (8 h). In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most cells of the sham brain, and was especially dense in hippocampal CA3 cells. Further induction of HSC70 mRNA was observed after reperfusion in the same cell populations, as in the case of HSP70 mRNA. HSC70 mRNA levels were significantly reduced in the caudate at 8 h when small amounts of HSP70 mRNA were still elevated. In the ipsilateral granule cells of the dentate gyrus and hippocampal CA3 cells a slight but significant induction of HSC70 mRNA was observed from 1 h to 1 day, while obvious induction of HSP70 mRNA never occurred. All the induced signals of HSP70 and HSC70 mRNA were diminished or returned to the sham level by 7 days, except for HSC70 mRNA in the caudate. These results are the first observations of the distribution of HSP70 and HSC70 mRNA after transient focal ischemia of rat brain. The results indicate that the temporal and quantitative differences in the maximum induction of HSP70 and HSC70 mRNA may relate to the different susceptibilities between cells of the caudate and cortex. Different roles under normal conditions and a general cooperative role in the recovery process from ischemic injury between HSP70 and HSC70 are suggested. The finding of selective induction of HSC70 mRNA in hippocampal cells may indicate that a stress response, which is not accompanied by HSP70 mRNA induction, occurs in the brain after transient ischemia.