Correlations between morphological changes in platelet aggregates and underlying endothelial damage in cerebral microcirculation of mice.

Abstract

BACKGROUND AND PURPOSE: The aim of this study was to test the hypothesis that, once formed, platelet aggregates may injure underlying cerebrovascular endothelium. Such injury could make the same site selectively attractive to the next wave of passing emboli or activated platelets. This vicious circle could account for repetitive, stereotypic symptoms in transient ischemic attacks. METHODS: In pial arterioles, minor endothelial injury was produced by a laser/dye technique. After various periods of platelet aggregation at the damaged site, the vessels were fixed in situ for electron microscopic study. The degree of platelet activation (rounded and/or degranulated forms) was evaluated by counting these forms in the electron photomicrographs. These counts were related to the degree of endothelial damage ascertained in the micrographs. Other statistical relations were also examined. RESULTS: Endothelial damage progressed in parallel with the duration of platelet aggregation and the degree of platelet degranulation at the site. Correlations were number of activated platelets versus degree of damage, r = .43, P < .03; duration of aggregation versus damage, r = .52, P < .01; and number of degranulated platelets versus the degree of endothelial damage, r = .83, P < .001. If an aggregate embolized, endothelial damage did not appear to progress. No correlation existed between the duration of exposure to the laser and the degree of injury. CONCLUSIONS: The parallel between changes in platelets and endothelial damage could represent either an effect of endothelium on platelets or an effect of platelets on endothelium. Although the former alternative cannot be totally ruled out, the observations seem to fit best the hypothesis that progressive endothelial damage can result from increasing activation and degranulation of overlying platelets.