DNA SCISSION AFTER FOCAL BRAIN ISCHEMIA - TEMPORAL DIFFERENCES IN 2 SPECIES

Background and Purpose Species- and model-dependent differences in cel l response to focal brain ischemia may underlie differences in adhesio n receptor expression. The aim of this study was to quantitatively eva luate the spatial and temporal distribution of dUTP incorporation into damaged DNA, as an indicator of ischemic injury, in the corpus striat um. Methods Cerebral ischemia was produced in 16 nonhuman primates and 19 rats by occluding the middle cerebral artery (MCA:O) with reperfus ion for various periods. In situ dUTP was incorporated into cells with DNA damage by terminal deoxynucleotidyl transferase (TdT), DNA polyme rase I, or the Klenow fragment of DNA polymerase. Dual immunolabeling experiments with immunoprobes against neuronal, vascular, or glial mar ker proteins were performed. Results Significant topographical differe nces in dUTP between the two species were seen. In both models the TdT and polymerase I regions changed characteristically during focal isch emia. The number and density of dUTP-labeled cells increased with time from MCA:O and were dramatically different between the species (2P<.0 01). By 2 hours of ischemia, the density of dUTP label was 48.8+/-10.3 cells/mm(2) in the primate and 2.4+/-0.8 cells/mm(2) in the rat (2P<. 05), but these values became nearly identical by 24 hours of reperfusi on. In the primate, 80.0+/-6.6% of labeled cells displayed microtubule -associated protein-2 antigen (at 2-hour MCA:O), while 1.8+/-0.5% were associated with microvessels at 24 hours of reperfusion. Conclusions In situ detection of DNA damage, accomplished by three methods, reveal s distinct temporal, topographical, and density differences in ischemi c injury to cells in the primate and the rat corpus striatum as a resu lt of MCA:O.