(Stroke. 1996;27:1386-1392.)
© 1996 American Heart Association, Inc.
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the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (H.-P.H., M.T., G.J. del Z.), and Protein Design Labs, Inc, Mountain View (E.L.B., N.T.), Calif.
Correspondence to Gregory J. del Zoppo, MD, Department of Molecular and Experimental Medicine, SBR17, The Scripps Research Institute, 10666 N Torrey Pines Rd, La Jolla, CA 92037.
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.
Department of Physiology, Louisiana State University Medical Center, Shreveport, La
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