Abstract
Introduction: Aging is a known risk factor for intracranial aneurysm rupture in human clinical studies. However, clinical studies only showed the association, but not the causality of aging and aneurysm rupture. Using our well-established mouse model, we directly tested the hypothesis that aging increases the rupture rate of aneurysms. Methods: We used both male and female C57BL/6J mice at 10 weeks and 18 months of age. We induced intracranial aneurysms by a combination of elastase injection and DOCA-salt hypertension. We compared the formation and rupture rates of intracranial aneurysms and the survival curve between young mice and aged mice of each sex. Results: Aged female mice had a higher rupture rate (86.7% vs 38.9%; P<0.05, Fisher’s exact test, Fig. A and B), and a higher formation rate (88.2% vs 62.1%; P<0.05, Fisher’s exact test) than young mice. Aged female mice had a lower survival rate than young mice (Fig. C). Aged male mice had both a higher rupture rate (94.1% vs 62.5%; P<0.05, Fig. D and E) and a higher formation rate (94.4% vs 64.0%; P<0.05) than young mice. There is a trend of a worse survival rate in aged male mice (Fig. F). Conclusions: Aging promotes both the formation and rupture of intracranial aneurysms in both male and female mice. These data agree with clinical observations and will serve as a basis for further investigation of the roles of the aging-related biological changes in the development of aneurysm rupture.
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