| Therapeutic induction of arteriogenesis in hypoperfused rat brain via granulocyte-macrophage colony-stimulating factor. | |
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MedLine Citation:
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PMID: 12835229 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Colony-stimulating factors (CSFs) have been shown to effectively induce arteriogenesis in the hindlimb. Moreover, clinical trials demonstrated positive effects of CSFs on arteriogenesis in patients with coronary artery disease. However, patients with cerebrovascular disease have not yet profited from treatments aimed at the growth of brain vessels. Thus far, angiogenesis studies have failed to demonstrate improvement of stroke outcome. Arteriogenesis differs from angiogenesis in that it substitutes arterial collaterals for the occluded artery. METHODS AND RESULTS: We tested in a novel brain arteriogenesis rat model (occlusion of vertebral plus left carotid artery [3-VO]) the application of CSFs or saline over 7 or 21 days. On 3-VO postmortem, latex perfusion demonstrated a time- and treatment-dependent arteriogenesis of the posterior cerebral artery (PCA). In saline-treated animals, the PCA diameter increased by 39%; in granulocyte-macrophage (GM)-CSF-treated animals, this increase was significantly faster (72% after 1 week). Functionally, saline-treated animals exhibited a decline of CO2 reactivity (mm Hg) from 1.48% to 0.1% compared with GM-CSF-treated animals (1.43% arterial pCo2 change after 1 week). This difference remained significant after 3 weeks. This functional improvement correlated with increased numbers of CD68-positive macrophages in histological sections of the PCA in GM-CSF--treated animals and only a few macrophages in saline-treated animals. CONCLUSIONS: To the best of our knowledge, this is the first report of stimulation of arteriogenesis in the brain. The subcutaneous application of GM-CSF led to functional improvement of brain hemodynamic parameters. |
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Authors:
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Ivo R Buschmann; Hans-Jörg Busch; Günter Mies; Konstantin-Alexander Hossmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-06-30 |
Journal Detail:
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Title: Circulation Volume: 108 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-05 Completed Date: 2003-09-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 610-5 Citation Subset: AIM; IM |
Affiliation:
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Albert Ludwigs University, Research Group for Experimental and Clinical Arteriogenesis, Department for Cardiology and Angiology, Breisacher Strasse 66, Freiburg im Breisgau, Germany. buschmann@med1.ukl.uni-freiburg.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Flow Velocity / drug effects Brain / blood supply*, drug effects, pathology Brain Ischemia / drug therapy*, pathology, physiopathology Cell Count Cell Division Cerebral Arteries / drug effects* Cerebrovascular Circulation / drug effects Collateral Circulation / drug effects Disease Models, Animal Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use* Immunohistochemistry Laser-Doppler Flowmetry Macrophages / pathology Neovascularization, Physiologic / drug effects* Rats Rats, Sprague-Dawley Vascular Patency / drug effects |
| Chemical | |
Reg. No./Substance:
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83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor |
| Comments/Corrections | |
Comment In:
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Curr Surg. 2004 Mar-Apr;61(2):146-51
[PMID:
15051253
]
Circulation. 2004 Jan 20;109(2):e4; author reply e4 [PMID: 14734507 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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