Schierling Wilma, Troidl Kerstin, Mueller Clemens, Troidl Christian, Wustrack Hanna, Bachmann Georg, Kasprzak Piotr M, Schaper Wolfgang, Schmitz-Rixen Thomas
Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
J Cereb Blood Flow Metab. 2009 Apr;29(4):726-37. doi: 10.1038/jcbfm.2008.165. Epub 2009 Jan 14.
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.
增加的流体切应力可显著增强外周动脉生成。因此，本研究旨在探讨在大鼠脑中增加的流体切应力是否也能刺激脑动脉生成。为了增加脑循环中的流体切应力，我们开发了不同的切应力模型，如双侧颈总动脉结扎（双结扎模型）、双侧颈动脉结扎后建立单侧动静脉瘘（两阶段方案，结扎-分流模型）以及单独建立单侧动静脉瘘（单分流模型）。通过定量磁共振成像分析在体内监测血流变化。通过磁共振成像和造影剂血管造影分析脑动脉生成。采用免疫组织化学方法检测单核细胞的增殖和聚集情况。在14天的观察期内，结扎-分流模型中基底动脉的血流最大增加5.5倍，瘘侧大脑后动脉的血流最大增加10.3倍。在所有切应力刺激的动脉中均发现了显著的血管生长。血管长度和直径与血流的比较分析表明脑侧支循环的生长与血管内流速升高之间存在相关性（R2 = 0.90/0.96）。免疫组织化学显示了动脉生成和单核细胞聚集的典型阶段。总之，我们提供的证据表明，流体切应力不仅是外周动脉生成的关键触发因素，也是脑动脉生成的关键触发因素。
