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Changes in regional cerebral blood flow were correlated with the distribution of histopathologic signs of brain injury in 35 rats after middle cerebral artery occlusion. Rats were allowed to survive for periods of up to 4 weeks after the operation, and we focused particular interest on the time course of blood flow changes from the initial ischemic events to the late stage of infarction. Regional blood flow was measured using [ 14 C]iodoantipyrine and a quantitative autoradiographic technique. Blood flow in regions with histologic signs of infarction (i.e., the lateral caudoputamen and adjacent neocortex) was below 0.238 ml/g/min, corresponding to 15% of normal values for those regions. In perifocal regions without infarction such as the medial caudoputamen and globus pallidus, cerebral blood flow was also reduced, but it never declined below 20% of its normal value. The decrease in cerebral blood flow was most marked during the first hours after occlusion. Thereafter, cerebral blood flow values gradually normalized, and at 4 weeks there were no significant differences compared with the contralateral side. The border between cortical regions with hypoperfusion and normal cerebral blood flow was rather sharp in the coronal plane, but in the sagittal plane there was a more gradual transitional region. The region with hypoperfusion, observed in the sagittal plane, was most widespread in the acute stage, and normalization of flow occurred particularly from anterior and posterior cortical regions toward the ischemic focus. The possibility for penumbral conditions in the cortex thus exists, particularly in the anterior and posterior borders of the infarction, and remains for several hours after the initial insult. Signs of hyperperfusion were present as an early phenomenon in the globus pallidus and caudoputamen, probably because of altered neuronal activity in line with previous studies or caused by hemodynamic changes in the territory of the occluded middle cerebral artery. Late hyperperfusion was seen in the same regions and also in the neocortex from 18 hours to 7 days after occlusion of the middle cerebral artery. Some of these areas with late hyperperfusion showed histologic signs of definite ischemic changes. The changes in cerebral blood flow occurring in and around a focus of cerebral ischemia have thus been determined in rats with occlusion of the middle cerebral artery. By observing the alterations over a long period of time, we have been able to identify the possibility of penumbral conditions in the early phase and the occurrence of reactive hyperemia in the late stage. (Stroke 1989;20:930-937) M iddle cerebral artery (MCA) occlusion (MCAO) in rats causes a region of focal cerebral ischemia followed by infarction. This model, introduced by Tamura et al, 1 is a very Received October 20, 1988; accepted January 26, 1989. useful tool for exploring the pathogenesis of infarction and for experiments designed to evaluate new therapeutic methods. It results in infarcts reproducible in size and location in t...

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Retinoic acid (RA) binds to a cytosolic protein distinguishable from the cellular retinol (R) binding protein. Recent studies, showing an influence by R and RA on genomic expression, suggest an interaction with the cell nucleus mediated by the specific binding proteins in a manner resembling that of steroid hormones. RA can irreversibly stimulate in vitro differentiation of teratocarcinoma cells and support early embryonic development in vitamin A depleted animals. This study demonstrates a saturable, highly specific and regional accumulation of RA in the neuroepithelium and developing CNS that occurs in early but not in late fetal development in the mouse. The results suggest that a binding protein, or some other cellular mechanism for accumulation of RA is expressed in the neural cells only during restricted periods of development. High levels are recorded also in regions where cranial neural crest cells are known to migrate, and later in the visceral arches and maxillary areas, the mesenchyme of which is known to be partly derived from migrating cranial neural crest cells. The specific accumulation of RA in embryonic neural and cranial neural crest cells is in line with animal experiments and human clinical data, showing that retinoids specifically impair CNS, eye, ear, and facial development.