Influence of platelet-activating factor on cerebral microcirculation in rats part 2. Local application

Background and Pupose-Platelet-activating factor (AF) is involved in the de velopment of secondary brain damage after ischemic and traumatic brain inju ry. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alte rations in cerebral microcirculation. Methods-Changes in cerebral microcirculation focusing on leukocyte-endothel ium interactions were quantified with the use of a closed cranial window mo del in Sprague-Dawley rats (n=33) by means of intravital fluorescence micro scopy. The brain surface was superfused with PAF in concentrations from 10( -3) (n=3) to 10(-12) mol/L (n=6) for 20 minutes (5 mL/h), Results-PAF 10(-4) mol/L (n=4) increased the number of rolling and adherent leukocytes in venules from 9.7+/-0.4 to 19.7+/-2.3 cells/100 mm min (P=NS versus control) and from 2.2+/-0.5 to 4.3+/-0.7 cells/100 mm min (P<0.05 ve rsus control), respectively. Lower concentrations did not elicit leukocyte- endothelium interactions. Vessel diameters remained unchanged except for a transient increase of arteriolar diameters during superfusion with PAF 10(- 4) and 10(-6) mol/L (n=6). Although only a limited area of the brain surfac e was exposed to PAF, the mediator induced a significant dose-dependent tra nsitory arterial hypotension and caused irreversible circulatory shock at t he high concentration (PAF 10(-3) mol/L), Arterial hypotension after admini stration of PAF 10(-3) mol/L could be attenuated by the intravenous pretrea tment with the PAF antagonist WEB 2170BS. Conclusions-PAF, when locally released after brain injury, can penetrate th e blood-brain barrier and induce systemic effects, including arterial hypot ension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, nut to be associated with disturbanc es of cerebral microcirculation or activation of leukocytes.