Increased Intravascular Flow Rate Triggers Cerebral Arteriogenesis

Abstract

Peripheral arteriogenesis is distinctly enhanced by increased fluid shear stress. Thus, the aim of this study was to investigate in the rat brain whether increased fluid shear stress can also stimulate cerebral arteriogenesis. To increase fluid shear stress in the cerebral circulation, we developed different shear stress models as the ligature of both common carotid arteries (Double-Ligature model), bilateral carotid ligature followed by creation of a unilateral arterio-venous fistula (two-stage protocol, Ligature-Shunt model), and unilateral arterio-venous fistula-creation alone (Solo-Shunt model). Blood flow changes were monitored in vivo by quantitative magnetic resonance imaging-analysis. Cerebral arteriogenesis was analyzed by magnetic resonance imaging and contrast agent-angiography. For proliferation and accumulation of mononuclear cells, immunohistochemistry was performed. During the 14 days-observation period, blood flow increased maximal by 5.5-fold in the A. basilaris and 10.3-fold in the fistula-sided A. cerebri posterior of the Ligature-Shunt model. Considerable vessel growth was found in all shear stress-stimulated arteries. Comparative analysis of vessel length and diameter versus blood flow indicated a correlation between the growth of cerebral collaterals and rising intravascular flow rates (R2=0.90/0.96). Immunohistochemistry showed the typical phases of arteriogenesis and accumulation of mononuclear cells. In conclusion, we provide evidence that fluid shear stress is not only the pivotal trigger of peripheral but also of cerebral arteriogenesis.