E-Selectin Appears in Nonischemic Tissue During Experimental Focal Cerebral Ischemia

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Abstract
Background and Purpose E-selectin participates in leukocyte-endothelial adhesion and the inflammatory processes that follow focal cerebral ischemia and reperfusion. The temporal and topographical patterns of microvascular E-selectin presentation after experimental focal cerebral ischemia are relevant to microvascular reactivity to ischemia. Methods The upregulation and fate of E-selectin antigen during 2 hours of middle cerebral artery occlusion (n=4) and 3 hours of occlusion with reperfusion (1 hour, n=4; 4 hours, n=6; 24 hours, n=6) were evaluated in the nonhuman primate. E-selectin and E:P-selectin immunoreactivities were semiquantitated with the use of computerized light microscopy video imaging and laser confocal microscopy. Results Three patterns of microvascular E-selectin expression, defined by the antibody E-1E4, were confirmed by complete elimination of E-1E4 binding after incubation with soluble recombinant human E-selectin: (1) Low immunoperoxidase intensity was observed in ischemic microvessels at 2 hours of occlusion extending to 4 hours of reperfusion (E-selectin/laminin=0.32±0.10). (2) A significant fraction of ischemic microvessels displayed high-intensity E-selectin signal by 24 hours of reperfusion (0.61±0.17) compared with control and nonischemic tissues (2P<.003). (3) In the contralateral nonischemic basal ganglia and other nonischemic tissues, low but significant E-selectin levels appeared by 24 hours of reperfusion (2P=.0005). The latter were further confirmed by an E:P-selectin immunoprobe. Conclusions E-selectin antigen is distinctively and significantly upregulated in nonhuman primate brain after focal ischemia and reperfusion. The late appearance of E-selectin in nonischemic cerebral tissues suggests stimulation by transferable factors generated during brain injury.