Role of fluid dynamics and inflammation in intracranial aneurysm formation

Abstract

The emergence of inflammation as a key mediator of aneurysmogenesis provides new opportunities to understand the processes underlying development of intracranial aneurysms (IA). Inflammation unifies the triptych influences of alterations in local flow, mechanical properties of the wall and biochemical mediators and opens new avenues for building robust predictive tools. This review discusses the impact of the inflammatory cascade during the formation of intracranial aneurysms, and its associated morphological, structural and mechanical changes especially in the setting of flow-induced endothelial dysfunction.

Keywords: computational fluid dynamics; inflammation; intracranial aneurysm; mechanics; ventricular remodeling.

Figure 1

Flow and wall shear stress.

Figure 2

Example of mesh generated for a computational fluid dynamics analysis in a rigid-boundary IA model. The size of the meshing elements, arrangement and topology condition the precision of the solution and the convergence and speed of the solving algorithm. Here we use tetrahedrons at the center of the lumen and smaller hexahedrons at the periphery to account for smaller variations near the fluid boundary layer.

Figure 3

Summary of the CFD procedure

Figure 4

Aneurysm propagation must be accompanied by cell proliferation and/or extracellular matrix production. Modeling of the process of ballooning out of an artery during aneurysmogenesis. Part of the artery (left) remodels to form a spherical aneurysm (right).

Figure 5

This cartoon summarizes the main steps of the establishment of inflammation in intracranial aneurysms. Going anti-clockwise: increased mechanical stress in aneurysm-prone regions is believed to trigger events that culminate in vascular dysfunctional, leaving the endothelium nude from anti-thrombotic protection. The inflammatory cascade then begins, with the expression of chemoattractants, pro-inflammatory cytokines and burgeoning of cell adhesion molecules at the surface of ECs, which attract peripheral blood mononuclear cells, including monocytes and T-cells. The complement is also activated through the classical pathway. Monocytes are able to adhere and transmigrate into the endothelium, which they would not do under normal conditions. They subsequently differentiate into macrophages, as observed in morphological studies of IA wall. The level of proteases in aneurysmal wall is increased and given literature knowledge about macrophages, there is good evidence that macrophages are responsible for the imbalance of proteases. During remodeling, the medial layer is destroyed, so is the internal elastic lamina, leading to lower mechanical properties and finally ballooning of the wall.