title: Influence of platelet-activating factor on cerebral microcirculation in rats: part 2. Local application.
abstract: OBJECTIVE
  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.
authors: Department of Neurosurgery, Grosshadern University Hospital, Ludwig-Maximilians University, Munich, Germany. Eberhard.Uhl@nc.med.uni-muenchen.de
authors: E
authors: E
authors: Uhl
authors: S
authors: S
authors: Pickelmann
authors: F
authors: F
authors: Röhrich
authors: A
authors: A
authors: Baethmann
authors: L
authors: L
authors: Schürer
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010841:Pia Mater / Q000098:blood supply; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C063964:bepafant