Abstract

Intracranial aneurysm (IA) is a frequent and generally asymptomatic cerebrovascular abnormality characterized as a localized dilation and wall thinning of intracranial arteries that preferentially arises at the arterial bifurcations of the circle of Willis. The devastating complication of IA is its rupture, which results in subarachnoid hemorrhage that can lead to severe disability and death. IA affects about 3% of the general population with an average age for detection of rupture around 50 years. IAs, whether ruptured or unruptured, are more common in women than in men by about 60% overall, and more especially after the menopause where the risk is double-compared to men. Although these data support a protective role of estrogen, differences in the location and number of IAs observed in women and men under the age of 50 suggest that other underlying mechanisms participate to the greater IA prevalence in women. The aim of this review is to provide a comprehensive overview of the current data from both clinical and basic research and a synthesis of the proposed mechanisms that may explain why women are more prone to develop IA.

Highlights

  • Intracranial aneurysm (IA) is defined as a localized dilation of cerebral arteries which preferentially forms at arterial bifurcation of the circle of Willis

  • Its activation leads to an increase in the expression of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1), which are responsible for the recruitment and adhesion of inflammatory cells to the endothelium where they produce proinflammatory cytokines such as tumor necrotizing factor alpha (TNFα), interleukin (IL)-1β, and IL-6 [56, 64–67]

  • One of them lies in the anatomic difference of the circle of Willis between men and women, with diameters and geometry of bifurcation of the arteries leading to higher hemodynamic stresses in women, driving more severe endothelial damage which favors IA formation

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Summary

Are Women Predisposed to Intracranial Aneurysm?

Intracranial aneurysm (IA) is a frequent and generally asymptomatic cerebrovascular abnormality characterized as a localized dilation and wall thinning of intracranial arteries that preferentially arises at the arterial bifurcations of the circle of Willis. IA affects about 3% of the general population with an average age for detection of rupture around 50 years. IAs, whether ruptured or unruptured, are more common in women than in men by about 60% overall, and more especially after the menopause where the risk is double-compared to men. These data support a protective role of estrogen, differences in the location and number of IAs observed in women and men under the age of 50 suggest that other underlying mechanisms participate to the greater IA prevalence in women.

INTRODUCTION
Woman Predisposition to Intracranial Aneurysm
IA Number and Localization
IA Growth and Rupture
Anatomical and Hemodynamic Parameters
MOLECULAR MECHANISMS OF ESTROGEN PROTECTION TO IA FORMATION
Estrogen Effect on Endothelial NO Synthase and Cerebral Artery Vasoreactivity
Estrogen Effect on Cerebral Artery Inflammation
Estrogen Effect on Cerebral Artery Oxidative Stress
Estrogen Effect on Cerebral Artery Matrix and Elastic Mechanical Properties
CONCLUSION
Findings
AUTHOR CONTRIBUTIONS
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