(Circulation. 1996;94:939-945.)
© 1996 American Heart Association, Inc.
Articles |
Endothelial ICAM-1 Expression Associated With Inflammatory Cell Response in Human Ischemic Stroke
the Department of Neurology (P.J.L., M.K.) and the Department of Pathology (O.C., A.P., M.-L.K.-L.), University of Helsinki (Finland).
Correspondence to Dr P.J. Lindsberg, Department of Neurology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
Background After focal brain ischemia, leukocytes adhere to the perturbed endothelium and are believed to aggravate reperfusion injury. Although ischemia-induced upregulation of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and P-selectin, has been observed in experimental animals, the mechanism of cerebral leukocyte infiltration and thus therapeutic possibilities to reduce it in humans are uncertain.
Methods and Results We counted the granulocytes, mononuclear phagocytes, and the percentages of cerebral microvessels expressing ICAM-1 by applying immunohistochemistry on brain sections showing a variable degree of neuronal damage from 11 human subjects who died 15 hours to 18 days after ischemic stroke and from normal control brains. In infarcted regions, granulocytes were detected as early as at 15 hours after injury (11.3 versus 0.5 cells/mm2 in noninfarcted hemisphere); their amount exceeded 200 cells/mm2 by 2.2 days but was back to normal level at 6.3 and 8.5 days. Acute infarctions (0.6 to 8.5 days) harbored significantly more ICAM-1–stained microvessels (up to 97% of microvessels at 1.8 days) than the noninfarcted hemisphere (P<.001), although the noninfarcted hemisphere (1.8 to 6.3 days) also showed higher ICAM-1 expression than controls. In the absence of ICAM-1 upregulation, macrophages (>200/mm2) were abundant in the core of neuronal damage at 17 and 18 days.
Conclusions The striking upregulation of endothelial ICAM-1 expression, functioning in concert with chemotactic factors, may cause granulocyte infiltration during the first 3 days after stroke. This study may support the usage and timing of antibody infusions to block endothelial adhesion molecules in an attempt to reduce leukocyte-induced damage in stroke.
Key Words: molecular biology • leukocytes • microcirculation • stroke
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