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.

Hui Meng, PhD and John Kolega, PhD