Intracranial aneurysm rupture: Mechanisms and prevention

Abstract

Pathological investigations have revealed degenerative changes in the vascular walls of intracranial aneurysms (IA) that lead to their rupture. Results from studies using an experimentally induced IA model have provided us a wide variety of evidence supporting the notion that IA is closely associated with inflammation. The inflammatory cascade begins with the activation of nuclear factor-kappa B (NF-κB) in endothelial cells, which up-regulates the expression of monocyte chemotactic protein-1 (MCP-1) recruiting macrophages into IA walls. Macrophages secrete matrix metalloproteinases (MMPs) -2 and -9 that promote the degradation of IA walls. It has also been demonstrated that treatment with statins and decoy oligodeoxynucleotides against NF-κB and Ets-r1 suppresses the development of rat IAs by inhibiting inflammatory reactions. On the other hand, computational fluid dynamics (CFD) has been recently applied to the analysis of flow patterns in IAs. The next issue to be solved is the identification of the linkage between flow patterns in IA and inflammatory responses in IA walls. Solving this issue will enable us to predict the probability of IA rupture and to prevent unruptured IAs from rupturing.