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(Stroke. 1999;30:880-886.)
© 1999 American Heart Association, Inc.

Original Contributions

Influence of Platelet-Activating Factor on Cerebral Microcirculation in Rats

Part 2. Local Application

Eberhard Uhl, MD; Sven Pickelmann, MD; Frank Röhrich, MD; Alexander Baethmann, MD Ludwig Schürer, MD

From the Department of Neurosurgery (E.U.), Department of Surgery (S.P.), and Institute for Surgical Research (A.B.), Grosshadern University Hospital, Ludwig-Maximilians University, Munich; Department of Neurosurgery, Zentralklinikum Bad Berka (F.R.); and Department of Neurosurgery, University Hospital, Mannheim (L.S.), Germany.

Correspondence to Eberhard Uhl, MD, Department of Neurosurgery, Grosshadern University Hospital, Marchioninistr 15, 81377 Munich, Germany. E-mail Eberhard.Uhl{at}nc.med.uni-muenchen.de

Background and Purpose—Platelet-activating factor (PAF) is involved in the development of secondary brain damage after ischemic and traumatic brain injury. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alterations in cerebral microcirculation.

Methods—Changes in cerebral microcirculation focusing on leukocyte-endothelium interactions were quantified with the use of a closed cranial window model in Sprague-Dawley rats (n=33) by means of intravital fluorescence microscopy. 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 versus 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 surface was exposed to PAF, the mediator induced a significant dose-dependent transitory arterial hypotension and caused irreversible circulatory shock at the high concentration (PAF 10^-3 mol/L). Arterial hypotension after administration of PAF 10^-3 mol/L could be attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS.

Conclusions—PAF, when locally released after brain injury, can penetrate the blood-brain barrier and induce systemic effects, including arterial hypotension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, not to be associated with disturbances of cerebral microcirculation or activation of leukocytes.

Editorial Comment

Part 2. Local Application

Frank M. Faraci, PhD, Guest Editor

Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa