Microvascular Basal Lamina Antigens Disappear During Cerebral Ischemia and Reperfusion

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Abstract
Background and Purpose Changes in vascular permeability are well-known and important consequences of cerebral ischemia. The development of edema and of petechial hemorrhage is connected to altered vascular integrity. A major part in microvascular integrity is played by the basal lamina. Methods The fates of the basal lamina components laminin, fibronectin, and type IV collagen during middle cerebral artery occlusion (2 hours, n=3) and occlusion (3 hours) with reperfusion (1 hour, n=3; 4 hours, n=3; and 24 hours, n=4) were evaluated in the nonhuman primate. Specific monoclonal antibodies against these components were used. The number and size distribution of the microvessels in each specimen were determined by video-imaging microscopy, and the relative fluorescence intensity of laminin was semiquantified by laser confocal microscopy. Basal lamina antigen presentations were compared by double-stain immunofluorescence histochemistry. Results The number of microvascular structures defined by the presence of each basal lamina antigen decreased significantly up to 24 hours of reperfusion ( P <.0001). The ratio of laminin-containing vessels between the ischemic and nonischemic territories decreased significantly from control (0.98±0.04) to 2 hours of ischemia (0.83±0.09) and 1 hour (0.79±0.08), 4 hours (0.77±0.06), and 24 hours of reperfusion (0.55±0.07). The ratio of fibronectin (cellular) and of collagen (IV)-containing vessels decreased from 0.98±0.04 to 0.75±0.1 and from 1.02±0.03 to 0.57±0.1, respectively. Mean laminin fluorescence intensity decreased from 76.1±6.0 U (controls) to 52.0±14.6 U (24 hours of reperfusion; P <.001). Conclusions The significant parallel losses of three basal lamina components, both in number and intensity, contribute to loss of microvascular integrity. These phenomena may be important for understanding cell extravasation and the hemorrhagic consequences of acute stroke.