Granulocyte-macrophage colony-stimulating factor-induced vessel growth restores cerebral blood supply after bilateral carotid artery occlusion.

Abstract

BACKGROUND AND PURPOSE:

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: Ulf C Schneider, Lothar Schilling, Helmut Schroeck, C Thomas Nebe, Peter Vajkoczy, Johannes Woitzik
• Journal: Stroke (Stroke) Vol. 38 Issue 4 Pg. 1320-8 (Apr 2007) ISSN: 1524-4628 [Electronic] United States
• PMID: 17332468 (Publication Type: Journal Article)

Chemical References

• Angiogenic Proteins
• Intercellular Signaling Peptides and Proteins
• Granulocyte-Macrophage Colony-Stimulating Factor
• Acetazolamide
• Antipyrine

Topics

• Acetazolamide
• Angiogenic Proteins (pharmacology, therapeutic use)
• Animals
• Antipyrine
• Capillaries (cytology, drug effects, physiology)
• Carotid Stenosis (complications, drug therapy, physiopathology)
• Cerebral Arteries (drug effects, physiopathology)
• Cerebrovascular Circulation (drug effects, physiology)
• Cerebrovascular Disorders (drug therapy, etiology, physiopathology)
• Disease Models, Animal
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology, therapeutic use)
• Hippocampus (blood supply)
• Intercellular Signaling Peptides and Proteins (pharmacology, therapeutic use)
• Laser-Doppler Flowmetry
• Male
• Microcirculation (drug effects, physiology)
• Neovascularization, Physiologic (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, physiology)
• Time
• Treatment Outcome