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 imaginganalysis. Cerebral arteriogenesis was analyzed by magnetic resonance imaging and contrast agentangiography. 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 (R 2 = 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.

Trans-illuminated laser speckle imaging of collateral artery blood flow in ischemic mouse hindlimb

“…3 Upon occlusion of a major artery, downstream pressure is reduced, causing an increase in the pressure gradient, blood flow, and shear stress along pre-existing collateral arteries that bypass the occlusion. Both the magnitude 4 and duration 5 of increased shear stress determine maximal collateral outgrowth and eventual resolution. Nonetheless, direct measurements of shear stress magnitude along individual collateral arteries have not been reported.…”

Tocotrienol Vitamin E Protects against Preclinical Canine Ischemic Stroke by Inducing Arteriogenesis

“…following vessel occlusion (Schierling et al, 2009) and the onset of adaptive arteriogenesis is marked by early-phase expression of protease inhibitor TIMP1 in growing collaterals of the brain (Hillmeister et al, 2008). In this work, TE supplementation significantly increased TIMP1 expression in both contralateral control and stroke-affected arterioles of the cerebral cortex.…”

“…Recent interest in the biological properties of tocotrienol has sharply risen because of the unique biological functions of this form of natural vitamin E not shared by the better known tocopherols, which have failed to live up to expectations in clinical trials (Miller et al, 2005;Schierling et al, 2009). At nanomolar concentrations, a-tocotrienol (aTCT) but not a-tocopherol, is a potent neuroprotective agent (Khanna et al, 2005b).…”

Brain Plasticity Following Ischemia: Effect of Estrogen and Other Cerebroprotective Drugs

“…Angiogenesis is related to hypoxia and results in new capillaries from the pre-existing vessels, whereas arteriogenesis is induced most importantly by increased shear stress that results in newly formed blood vessels (Heil and Sharper, 2004;Heil et al, 2006;Schierling et al, 2009;Xiong et al, 2010); however, the differences in the cause and the result is usually are not this clear cut. Angiogenesis has a major role in brain regeneration after ischemia as increased blood supply directly enhances cell survival and regenerative processes (Font et al, 2010).…”