Role of the complement cascade in cerebral aneurysm formation, growth, and rupture

Abstract

A B S T R A C TRupture of intracranial aneurysms is the most common cause of nontraumatic subarachnoid hemorrhage, but the intricate neuroinflammatory processes which contribute to aneurysm pathophysiology are not well-understood. Mounting evidence has implicated the complement cascade in the progression of aneurysms from their formation to rupture. In this article, we identify and review studies that have sought to determine the role of the complement system in the aneurysm pathogenesis. The studies were generally conducted by immunhistological analyses on aneurysm tissue collected intraoperatively, and multiple components of the complement cascade and its modulators were identified in specific regions of the aneurysm wall. The results of the studies suggest that the complement cascade is locally upregulated and disinhibited in the perianeurysmal environment, and that it contributes to chronic as well as acute immunological damage to the aneurysm wall. In the future, understanding the mechanisms at work in complement-mediated damage is necessary to leading the development of novel therapies.

Morphological and Hemodynamic Differences Between Ruptured and Unruptured Vertebral Artery Dissecting Aneurysms: A Two-Center Retrospective Study

“…Once the damage occurred, SMCs initially respond to higher WSS by migrating from the media to the intima, and in response to local signals, they change from a contractile phenotype to a secretory type, increasing nuclear factor kappa beta (NF-κβ), interleukin-1beta (IL-1β), tumor necrosis factor-α and matrix metals. Protease was produced, and the apoptotic pathway was initiated 34 . IL-1β was found to locally act on SMCs in mouse aneurysm model, resulting in apoptosis of SMCs, weakening of elasticity layer, and aneurysm rupture 35 .…”

High Wall Shear Incites Cerebral Aneurysm Formation and Low Wall Shear Stress Propagates Cerebral Aneurysm Growth

“…Flow acceleration at bifurcation points produces a hemodynamic environment characterized by high WSS which triggers initiation of aneurysmal dilation. In experimental models of CAs [4,[15][16][17], increased cerebral blood flow and systemic hypertension are necessary prerequisites for the initiation of CA formation (Table 1) [48,56,58,60,[64][65][66][67][68][69][70][71][72][73]. Likewise, Kulcsar et al analyzed the hemodynamics of a cerebral vasculature in three patients before and after the development of an intracranial aneurysm and observed that intracranial aneurysm consistently formed at locations characterized by high WSS [74].…”

Shedding the Light on the Natural History of Intracranial Aneurysms: An Updated Overview

“…Modified VSMCs are spider-like shaped, split, and incapable of excreting collagen for the extracellular matrix (ECM). Proinflammatory VSMCs also upregulate the NF-κβ, IL-1β, TNF-α, and MMPs, leading to ECM transformation, proteolytic destruction, and thinning of the tunica media [ 51 , 52 , 53 , 54 ]. VSMCs move to the intima layer and proliferate, resulting in intimal degeneration, namely myointimal hyperplasia [ 55 , 56 ].…”