P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion.
OBJECTIVE
Polymorphonuclear leukocytes have been implicated in the development of the "no-reflow" phenomenon after focal cerebral ischemia and reperfusion. To further understand the role of granulocytes in microvascular occlusions, the responses of the granulocyte-endothelial cell adhesion molecules P-selectin and intercellular adhesion molecule-1 during middle cerebral artery ischemia and reperfusion were examined in a primate model.


METHODS
Twelve adolescent male baboons were used for 2-hour middle cerebral artery occlusion (n = 3) or for 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n = 3) reperfusion, and three separate unoperated primates served as controls. A quantitative immunohistochemical study of the microvascular distribution of P-selectin and intercellular adhesion molecule-1 was performed using 10-microns frozen sections from basal ganglia analyzed with computerized light microscopy video imaging.


RESULTS
Significant (P < .05) persistent upregulation of P-selectin (beginning during ischemia) and transient upregulation of intercellular adhesion molecule-1 (at 1 and 4 hours of reperfusion) were observed on endothelium of selected post-capillary microvessels of the ischemic lenticulostriate artery territory. Platelet accumulation also occurred in this territory and was responsible for a significant proportion of the nonendothelial P-selectin signal at 24 hours after reperfusion.


CONCLUSIONS
Focal cerebral ischemia/reperfusion stimulates endothelial P-selectin and intercellular adhesion molecule-1 expression in brain microvessels in the ischemic zone, which may contribute to enhanced leukocyte adherence and persistent activation.
Okada
Y
Y
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.
Copeland
B R
BR
Mori
E
E
Tung
M M
MM
Thomas
W S
WS
del Zoppo
G J
GJ
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002536:Cerebral Arteries / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D008833:Microcirculation; D019007:P-Selectin; D010215:Papio; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D015424:Reperfusion
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1