PROLONGED EXPRESSION OF HSP70 MESSENGER-RNA FOLLOWING TRANSIENT FOCALCEREBRAL-ISCHEMIA IN TRANSGENIC MICE OVEREXPRESSING CUZN-SUPEROXIDE DISMUTASE

The distribution of heat shock protein hsp70 mRNA after 10 min of midd le cerebral artery (MCA) occlusion was investigated through in situ hy bridization in transgenic (Tg) mice overexpressing CuZn-superoxide dis mutase (CuZn-SOD) and in control nontransgenic (nTg) littermates. In t he ischemic cortex of nTg mice, hsp70 mRNA was detected 1 h after repe rfusion and was observed for up to 6 h. In Tg mice, however, it was st ill detectable within the cortex even at 24 h. In the caudate putamen, hsp70 mRNA appeared at 1 h and was present for up to 6 h in both nTg and Tg mice. Although hsp70 mRNA was detected in the thalamus only at 1 h in nTg mice, it was observed for up to 6 h in Tg mice. Similarly, hsp70 mRNA was detected in the hippocampus of nTg mice only at 1 h, wh ereas it was detected in Tg mice at 1 h and continued up to 24 h, with high intensity in the CA1 subfield. Despite the significant amounts o f hsp70 mRNA in both Tg and nTg mice following ischemia, there was no observable neuronal necrosis (as assessed using hematoxylin and eosin staining) for up to 7 days. Cortical cerebral blood flow (CBF), measur ed by laser-Doppler flowmetry, did not differ between nTg and Tg mice during ischemia and reperfusion, despite exhibiting hyperemia followin g hypoperfusion. These results suggest that oxidative stress affects t he expression of hsp70 following temporary focal ischemia. An alterati on in oxidation stress, which resulted from reduced levels of superoxi de radicals in the presence of the CuZn-SOD transgenes, may permit the prolonged expression of hsp70. This prolonged expression of hsp70 mRN A in cortex cannot be accounted for by changes of CBF in Tg mice durin g ischemia and reperfusion.