P-SELECTIN AND INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION AFTER FOCAL BRAIN ISCHEMIA AND REPERFUSION

Background and Purpose Polymorphonuclear leukocytes have been implicat ed in the development of the ''no-reflow'' phenomenon after focal cere bral ischemia and reperfusion. To further understand the role of granu locytes in microvascular occlusions, the responses of the granulocyte- endothelial cell adhesion molecules P-selectin and intercellular adhes ion molecule-1 during middle cerebral artery ischemia and reperfusion were examined in a primate model. Methods Twelve adolescent male baboo ns 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) r eperfusion, and three separate unoperated primates served as controls. A quantitative immunohistochemical study of the microvascular distrib ution of P-selectin and intercellular adhesion molecule-1 was performe d using 10-mum frozen sections from basal ganglia analyzed with comput erized light microscopy video imaging. Results Significant (P<.05) per sistent upregulation of P-selectin (beginning during ischemia) and tra nsient upregulation of intercellular adhesion molecule-1 (at 1 and 4 h ours of reperfusion) were observed on endothelium of selected postcapi llary microvessels of the ischemic lenticulostriate artery territory. Platelet accumulation also occurred in this territory and was responsi ble for a significant proportion of the nonendothelial P-selectin sign al at 24 hours after reperfusion. Conclusions Focal cerebral ischemia/ reperfusion stimulates endothelial P-selectin and intercellular adhesi on molecule-1 expression in brain microvessels in the ischemic zone, w hich may contribute to enhanced leukocyte adherence and persistent act ivation.