Hemodynamics Induced Intracranial Aneurysm Initiation: Mechanism and Model Exploration (Completed 2013)
The role of high wall shear stress/positive wall shear stress gradient on intracranial aneurysm (IA) initiation was investigated.
-Molecular mechanism was explored using a rabbit hemodynamic IA model:
-High wall shear stress/positive wall shear stress gradient leads to increased endothelial nitric oxide synthase in the intima and increased superoxide in the media at the basilar tip, the zone of IA initiation.
-Nitric oxide from endothelial nitric oxide synthase and smooth muscle derived superoxide independently are important for IA initiation.
-Both nitric oxide and superoxide affect a common pathway involving loss of smooth muscle contractility, leading to MMP production and IA damage.
-To improve study of molecular mechanism in animal models, bilateral common carotid artery ligation was attempted in the rat and compared against the existing rabbit model:
-Hemodynamic analysis via computational fluid dynamics was successfully demonstrated in the rat.
-Rat ligation fails to generate IA damage seen in rabbits, in part due to differences and variability in vascular geometry around the basilar tip.
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