title: Granulocyte-macrophage colony-stimulating factor-induced vessel growth restores cerebral blood supply after bilateral carotid artery occlusion.
abstract: OBJECTIVE
  Hemodynamic compromise due to occlusive cerebrovascular disease is associated with an increased stroke risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to stimulate collateral blood vessel growth in various models of hemodynamic compromise. The purpose of this study was to investigate the effects of GM-CSF on cerebral hemodynamics and vessel growth in a rat model of chronically impaired cerebral blood flow (CBF).
  
  
  METHODS
  Male Sprague-Dawley rats underwent sequential bilateral carotid artery occlusion (BCO) and were treated with GM-CSF or saline for 6 weeks. Sham-occluded animals served as a control group. Baseline CBF was measured by iodo[(14)C]antipyrine autoradiography, and cerebrovascular reserve capacity was assessed by laser-Doppler flowmetry after application of 20 mg/kg body weight acetazolamide. The capillary density and arterioles immunopositive for alpha-smooth muscle actin were counted on brain sections. The cerebral angioarchitecture was visualized with a latex perfusion technique.
  
  
  RESULTS
  Baseline CBF as measured by iodo[(14)C]antipyrine autoradiography was not affected by BCO. The cerebrovascular reserve capacity, however, was significantly impaired 1 week after BCO. CBF and cerebrovascular reserve capacity recovered completely in GM-CSF-treated animals but not in solvent-treated animals. Histologic analysis of the hippocampus revealed integrity of the hypoxia-vulnerable neurons in all animals. The capillary density showed a very mild increase in GM-CSF-treated animals. However, the number of intraparenchymal and leptomeningeal arterioles was significantly higher in GM-CSF-treated animals than in both other groups.
  
  
  CONCLUSIONS
  Long-term GM-CSF treatment in a BCO model in rats leads to restoration of impaired cerebral hemodynamics and accompanies structural changes in the resistance-vessel network.
authors.affiliation: Department of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Ulf C
authors.initials: UC
authors.lastname: Schneider
authors.forename: Lothar
authors.initials: L
authors.lastname: Schilling
authors.forename: Helmut
authors.initials: H
authors.lastname: Schroeck
authors.forename: C Thomas
authors.initials: CT
authors.lastname: Nebe
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: Johannes
authors.initials: J
authors.lastname: Woitzik
mesh_terms: D000086:Acetazolamide; D042501:Angiogenic Proteins / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000983:Antipyrine; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016893:Carotid Stenosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000098:blood supply; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013995:Time; D016896:Treatment Outcome
chemical_list: D042501:Angiogenic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000086:Acetazolamide; D000983:Antipyrine