Two strategies were used to estimate the blood flow threshold for focal cerebral infarction in spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery and common carotid artery occlusion (MCA/CCAO). The first compared the volume of cortical infarction (24 h after ischemia onset) to the volumes of ischemic cortex (image analysis of [14C]iodoantipyrine CBF autoradiographs) perfused below CBF values <50 (VIC50) and <25 ml 100 g−1 min−1 (VIC25) at serial intervals during the first 3 h of ischemia. The infarct process becomes irreversible within 3 h in this model. In the second, measurements of CBF at the border separating normal from infarcted cortex at 24 h after ischemia onset were used as an index of the threshold. During the first 3 h of ischemia, VIC50 increased slightly to reach a maximum size at 3 h that closely matched the 24 h infarct volume. VIC25, in contrast, consistently underestimated the infarct volume by a factor of 2–3. CBF at the 24 h infarct border averaged 50 ml 100 g−1 min−1. Taken together, the results indicate that the CBF threshold for infarction in SHRs approaches 50 ml 100 g−1 min−1 when ischemia persists for ≥3 h. This threshold value is approximately three times higher than in primates. Since cortical neuronal density is also threefold greater in rats than in primates, the higher injury threshold in the rat may reflect a neuronal primacy in determining the brain's susceptibility to partial ischemia.
Mechanism of increased sensitivity to cerebral ischemia following carotid artery occlusion in stroke-prone spontaneously hypertensive rats: importance of genetic factors.