Abstract 3678: Decreased Incidence of Cerebral Aneurysm Rupture with the use of Aspirin in an Animal Model
Introduction: A growing amount of literature in both human and animal models supports the hypothesis that chronic inflammation is a key component in cerebral aneurysm (CA) development and rupture. Aspirin has a well-documented history of safety and pharmacologic studies reveal that aspirin’s anti-inflammatory properties impede several pathways that are implicated in aneurysm growth and rupture. Recently, our secondary analysis of the International Study of Unruptured Intracranial Aneurysms showed a significant association between aspirin use and decreased incidence of subarachnoid hemorrhage. We aimed to determine whether an animal model could be used to investigate the mechanisms of aspirin’s protective effects and to refine the molecular targets for prevention of CA rupture. As an initial step, we tested whether aspirin could reduce the incidence of aneurysmal rupture in our mouse CA model.
Method: We generated CAs by a combination of induced hypertension and local elastic lamina disruption. In male C57/B6 mice, systemic hypertension was induced by desoxycorticosterone acetate-salt treatment. Elastase (35mU) was injected stereotaxically in the right basal cistern to produce disruption of elastic lamina. One week after aneurysm induction surgery, mice were given 30mg/kg daily aspirin by gavage. Control animals were given the same volume of water. Aneurysmal rupture were detected by daily clinical evaluation and confirmed by brain dissection. All animals were sacrificed three weeks after elastase injection to determine rate of CA formation.
Results: For the control group (N=10), 80% developed CA by 3 weeks. 40% of the control animals had ruptured aneurysm that caused neurological deficits prior the end of the study. Similarly for the aspirin group (N=10), 80% developed CA by 3 weeks. However, only 20% of the animals who received daily aspirin developed cerebral aneurysm rupture.
Conclusion: Similar to our previous human epidemiological study, we observed a strong trend of lower rate of CA rupture with daily aspirin use in our animal model. Further investigations to confirm this finding and studies on the mechanistic basis of aspirin’s protective effect are underway. Using this animal model with established rates of CA development and rupture allows us to test other anti-inflammatory agents and conduct studies on specific molecular targets for the prevention of aneurysm rupture.
- © 2012 by American Heart Association, Inc.