Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

Abstract

Intracranial aneurysms are a life-threatening cerebrovascular pathology with a probability of spontaneous rupture. Current intervention techniques carry inherent risk. Recent investigation has reinforced inflammation's role in the pathophysiological process of cerebral aneurysms. These data suggest alternative diagnostic and noninvasive therapeutic strategies. Furthermore, novel characteristics of the underlying disease have been elucidated through distinct bioinformatic and gene expression profile analyses. This article will emphasize the most recent investigation, highlighting findings of clinical significance and etiological relevance.

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

“…Immune cells are locally recruited through enhanced expression of vascular-derived adhesion molecules, including ICAM1 (intercellular adhesion molecule 1), VCAM1 (vascular cell adhesion molecule 1), and P-selectin, and the chemokines MCP-1 (monocyte chemoattractant protein 1) and IL-8. 105,106 At vascular sites, they secrete proinflammatory cytokines, including IL-1β, TNF-α, and IL-6 that disrupt endothelial and vascular smooth muscle cell homeostasis through NF-κB signaling, drive direct matrix degradation through MMP2 and MMP9 secretion, and generate reactive oxidative species-mediated oxidative stress. 105,106 The exact factors promoting this localized immune recruitment remain unclear, but this response likely represents an attempt for vascular repair following disruptions by hemodynamic-driven factors or other aversive stimuli.…”

“…105,106 At vascular sites, they secrete proinflammatory cytokines, including IL-1β, TNF-α, and IL-6 that disrupt endothelial and vascular smooth muscle cell homeostasis through NF-κB signaling, drive direct matrix degradation through MMP2 and MMP9 secretion, and generate reactive oxidative species-mediated oxidative stress. 105,106 The exact factors promoting this localized immune recruitment remain unclear, but this response likely represents an attempt for vascular repair following disruptions by hemodynamic-driven factors or other aversive stimuli.…”

Biophysical targeting of high‐risk cerebral aneurysms

“…; low-shear and recirculating flow patterns 1,12,13 ) as well as pathological biological processes,(e.g. ; inflammation and thrombosis), these two features and the link between them has been a subject of great research [14][15][16] . Local biological features associated with high risk of rupture; which include luminal thrombosis and white blood cell infiltration 1,16 ; are tightly related to interactions between a disrupted or activated endothelium and flowing blood cells, either platelet or white blood cells, (Figure 1A,B&D).…”

“…; inflammation and thrombosis), these two features and the link between them has been a subject of great research [14][15][16] . Local biological features associated with high risk of rupture; which include luminal thrombosis and white blood cell infiltration 1,16 ; are tightly related to interactions between a disrupted or activated endothelium and flowing blood cells, either platelet or white blood cells, (Figure 1A,B&D). Such interactions occur also in regular inflammation processes and vessel thrombosis scenarios and thus targeted therapeutics have been developed based on utilizing specific biomolecular interactions between platelet/WBC and an inflamed/injured endothelium.…”