Structural Fragility of Cerebral Aneurysms: A Comparative Analysis of Unruptured & Ruptured Aneurysms

Abstract

Ongoing studies to understand the mechanisms behind intracranial aneurysm (IA) pathogenesis characterize intracranial aneurysm as a maladaptive chronic inflammatory disease. An overwhelmingly large number of studies implicate inflammation as a crucial driver of aneurysmal growth and attendant rupture. The induction of aneurysmal formation begins with endothelial damage, which secondarily activates a progressive inflammatory response that compromises the structural integrity of the vessel wall. Pivotal consequences of this inflammatory response is a disintegration of the internal elastic lamina, myointimal hyperplasia, and vascular smooth muscle cell (vsmc) phenotypic modulation and subsequent apoptosis. Interestingly, analysis of gene expression profiles in patients with intracranial aneurysms commonly highlight a differential expression of genes related to inflammatory/immune responses, cell adhesion, and muscle contraction. A detailed understanding of intracranial aneurysmal pathogenesis may be possible by analyzing morphological differences in aneurysmal structure between unruptured and ruptured lesions. As such, in this review, we have attempted to understand sequential adaptations of the aneurysmal wall during various periods of growth, development and rupture by providing evidence for structural, genetic, and molecular differences between unruptured and ruptured intracranial aneurysm.