Abstract
Between 3.6% and 6.0% of the population has an intracranial aneurysm. The mechanisms underlying intracranial aneurysm formation and rupture are not fully known. Several rodent models have been developed to better understand intracranial aneurysm pathophysiology. Hypertension, hemodynamic changes, and vessel injury are all necessary for aneurysm induction; however, multiple invasive procedures may disrupt an animal’s physiology. Therefore, we hypothesized that our method for inducing hypertension could be modified to create a simpler model. We previously developed a highly reproducible murine model of intracranial aneurysm formation and rupture that involves hemodynamic changes through ligation of the left common carotid artery, vessel wall degradation using elastase and a lysyl oxidase inhibitor, and hypertension through a high-salt diet, continuous angiotensin II infusion, and right renal artery ligation. In order to create a simpler model, we sought to eliminate renal artery ligation. We assessed aneurysm formation, aneurysm rupture, and blood pressure in two separate cohorts of C57BL/6 mice: one cohort underwent our model as above, while another cohort did not receive right renal artery ligation. Our results demonstrate that intracranial aneurysm formation and rupture rates did not differ between each group. Further, the blood pressures between cohorts did not differ at various timepoints in the model. Both cohorts, however, did have a significant increase in blood pressure from baseline, suggesting that renal artery ligation is not needed for inducing hypertension. These findings demonstrate that our murine model can be modified to eliminate right renal artery ligation. Thus, we propose this modification to our murine model for studying intracranial aneurysm pathophysiology.
Highlights
Intracranial aneurysms (IA) affect between 3.6-6.0% of the population [1]
The modified model, which does not include right renal artery (RRA) ligation, did not affect aneurysm formation or rupture compared to the established model (Figures 1, 2)
Performing left common carotid artery (LCCA) ligation only does not affect aneurysm formation compared to ligating both the LCCA and RRA
Summary
Intracranial aneurysms (IA) affect between 3.6-6.0% of the population [1]. IA rupture results in subarachnoid hemorrhage, a devastating condition with up to 51% mortality [2]. We previously described a highly reproducible murine model for IA formation and rupture [5] This model includes hemodynamic changes, hypertension, and vascular wall degradation, all key features of human IA [13]. At the time of this second procedure, mice are fed a diet containing high salt content (8% sodium chloride) and β-aminopropionitrile (BAPN, 0.12%), a lysyl oxidase inhibitor that facilitates vessel wall degradation [5,14]. This methodology results in IA formation and rupture rates of 67-90% and 50-61%, respectively [5,15]. While this murine model is highly reproducible, we believe the model can be simplified to have fewer confounding effects on the mouse’s baseline physiology
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