• Mami Ishikawa, Dianne Cooper, Janice Russell, James W Salter, John H Zhang, Anil Nanda, and D Neil Granger.
• Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130-3932, USA.
• Stroke. 2003 Jul 1;34(7):1777-82.

Background And PurposeCirculating blood cells have been implicated in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury and stroke. The objective of this study was to define the magnitude and molecular determinants of the platelet- and leukocyte-endothelial cell adhesive interactions induced by I/R in the mouse brain.MethodsBilateral common carotid artery occlusion was induced for 1 hour in C57BL/6 mice, followed by either 40 minutes or 4 hours of reperfusion. Fluorescent platelets were administered intravenously, and the frontal brain surface was observed with intravital fluorescence microscopy. Leukocyte-endothelial cell adhesion was monitored with the use of rhodamine-6G.ResultsIschemia followed by 40 minutes of reperfusion resulted in the rolling (125.1+/-23.6/mm2) and firm adhesion (109.5+/-25.8/mm2) of leukocytes but not platelets in venules. However, with 4 hours of reperfusion, rolling (138.8+/-24.6/mm2) and firm adhesion (153.7+/-22.3/mm2) of platelets were detected, and this was accompanied by a more intense recruitment of rolling (374.5+/-54.6/mm2) and adherent (445.2+/-57.1/mm2) leukocytes. In mice deficient in either P-selectin (P-selectin-/-) or intercellular adhesion molecule-1 (ICAM-1) (ICAM-1-/-), the I/R-induced platelet-endothelial cell (by 80% and 60%, respectively) and leukocyte-endothelial cell (by 84% and 78%, respectively) interactions were significantly blunted compared with those of wild-type mice.ConclusionsThese findings indicate that I/R promotes the adhesion of both platelets and leukocytes in cerebral venules, with the accumulation of adherent leukocytes preceding the recruitment of platelets. Both P-selectin and ICAM-1 contribute to the inflammatory and prothrombogenic state induced by cerebral I/R.

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