Platelet-activating factor mediates ischemia-induced leukocyte-endothelialadherence in newborn pig brain

The authors examined the involvement of platelet-activating factor (PAF) in mediating leukocyte adherence to brain postcapillary pial venules and alte ring blood-brain barrier (BBB) permeability during basal conditions and dur ing reoxygenation after asphyxia in newborn piglets. Intravital epifluoresc ence videomicroscopy, closed cranial windows, and labeling of leukocytes wi th rhodamine 6G allowed us to obtain serial measurements of adherent leukoc ytes within postcapillary venules. Blood-brain barrier breakdown was determ ined by optical measures of cortical extravascular fluorescence intensity a fter intravenous sodium fluorescein. Superfusion of PAF over the cortex ind uced a dose-dependent increase in leukocyte adherence to cerebral venules a nd leakage of fluorescein; with 1 mu mol/L PAF, the magnitude of adherence and BBB breakdown was similar to that seen during reoxygenation after 9 min utes of asphyxia. Both adherence and loss of BBB integrity resulting from e ither exogenous PAF or asphyxia-reoxygenation could be significantly attenu ated by intravenous administration of WEB 2086, a PAF receptor antagonist. Window superfusion of superoxide dismutase with PAF attenuated PAF-induced increases in adherence and associated fluorescein leakage. These findings i ndicate that PAF exhibits proinflammatory effects in piglet brain and that PAF contributes to leukocyte adherence and BBB breakdown after cerebral isc hemia. These PAF effects are mediated by increases in superoxide radical ge neration.