Abstract W MP44: Investigations Using a Combination of Computational Fluid Dynamics Technique and an Animal Model of Experimentally Induced Cerebral Aneurysms Suggest Important Roles of Wall Shear Stress on the Cerebral Aneurysm Development

Abstract

We have a series of reports suggesting that an increase in hemodynamic factors, especially wall shear stress, plays a central role in cerebral aneurysm development. We show here the effect of wall shear stress on the cerebral aneurysm growth, using computational fluid dynamics (CFD) analyses and an animal model of experimentally induced cerebral aneurysms. 3-dimentional CT angiographic images of 34 human cerebral aneurysms were used for CFD analyses. Measured flow rates derived from physiological data of individual patients, but not theoretically assumed rates, were used as inlet boundary conditions because there exists a significant influence of inlet boundary conditions between measured and theoretically assumed values on hemodynamics in human cerebral aneurysms as we reported previously. CFD analyses in human cerebral aneurysms frequently indicated an increase in wall shear stress at the aneurysm orifice. Moreover, if the arterial geometry around the aneurysm is virtually reconstructed just before the aneurysm induction by artificial removal of the aneurysm, the enhanced magnitude of wall shear stress and gradient oscillatory number was observed near the apex of arterial bifurcation where the aneurysm was removed. In animal experiments, we examined the effect of blockage in the P2X4 purinoceptor, the vascular endothelial shear-sensor, on the frequency of aneurysm induction after aneurysm-inducing surgery, using P2X4 knockout mice (n=19) and wild type mice (n=21). The incidence of induced aneurysm formation in P2X4 knockout mice was significantly lower than in wild types (p<0.02). Immunohistochemical examinations indicated that the immunoreactivity of MCP-1, which is closely associated with inflammatory responses during aneurysm formation, was weaker in P2X4 knockout mice than in wild types. These data suggest that during aneurysm formation, vascular endothelial cells might sense excessively high levels of wall shear stress over physiological limit, which may initiate damage to vascular components, leading to aneurysm development. A combination of CFD simulation in the human cerebral aneurysm and an animal model of experimentally induced cerebral aneurysms may be a good tool for the study of cerebral aneurysm formation.