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(Stroke. 2007;38:1320.)
© 2007 American Heart Association, Inc.

Original Contributions

Granulocyte-Macrophage Colony-Stimulating Factor–Induced Vessel Growth Restores Cerebral Blood Supply After Bilateral Carotid Artery Occlusion

Ulf C. Schneider, MD; Lothar Schilling, MD, PhD; Helmut Schroeck, PhD; C. Thomas Nebe, MD; Peter Vajkoczy, MD Johannes Woitzik, MD

From the Department of Neurosurgery (U.C.S., L.S., P.V., J.W.) and Institute of Clinical Chemistry (C.T.N.), University Hospital Mannheim, Mannheim, and the Department of Physiology (H.S.), University of Heidelberg, Heidelberg, Germany.

Correspondence to Dr Johannes Woitzik, Department of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. E-mail Johannes.woitzik{at}nch.ma.uni-heidelberg.de

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[¹⁴C]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 -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[¹⁴C]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.

Key Words: angiogenesis • cerebral blood flow • growth factors • stroke • vasculature

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