Focal cerebral ischemia in the rat: topography of hemodynamic and histopathological changes.

We studied local cerebral blood flow, as measured by autoradiography with digital image processing and by tissue morphology, in six rats 4 hours after occlusion of the proximal middle cerebral artery. A consistent, three-dimensional pattern of graded reductions in local cerebral blood flow involved the affected hemisphere, with a densely ischemic zone (local cerebral blood flow less than 3 ml/100 gm/min) in the dorsolateral caudate putamen and the adjacent frontoparietal cortex. In the frontoparietal cortex, the normal laminar pattern of local cerebral blood flow was disrupted, and there was a transcortical gradient in flow, with pronounced ischemia in deeper layers and relatively preserved superficial flow. Comparisons of autoradiographic findings with histopathological abnormalities in adjacent frozen sections showed that the region of ischemic damage corresponded closely with the area of greatest reduction in blood flow. Although around this region local cerebral blood flow increased centrifugally, a striking finding was that flow density changed abruptly (a tenfold variation in flow within a 1 to 2 mm interval) at the edge of the pathological lesion. Penumbral conditions may therefore exist in only a very narrow zone 4 hours after onset of focal ischemia. After occlusion of a major cerebral artery, the pattern of local cerebral blood flow changes appears to depend on interactions among vascular architecture, reductions in perfusion pressure, alterations in metabolic demands, and variations in local vascular resistance.