A mouse model of intracranial aneurysm: Cisterna magna elastase injection combined with hypertension and carotid artery ligation

Abstract: BACKGROUND: The existing mouse model of ruptured intracranial aneurysm (IA) involves stereotactic injection of elastase into basal cistern. Cisterna magna (CM) injection is also a well-established and reliable drug delivery method. We propose a mouse model inducing IA rupture through injection of elastase into CM, combined with hypertension and carotid ligation. MATERIALS AND METHODS: Male C57/BL6 mice underwent injection of 2.5 µL bromophenol blue through stereotaxis or CM to assess the accuracy and stability of both methods. For aneurysm induction, left common carotid artery ligation was performed, and hypertension was induced. CM injection was performed using 2.5 or 5 µL of elastase. Mice with neurological symptoms or 3 weeks after modeling received bromophenol blue/gelatin perfusion to observe the formation and rupture of aneurysm. Hematoxylin and eosin, Masson, and immunohistochemical staining were performed to observe IA histopathological features. RESULTS: CM injection resulted in more stained arteries around the circle of Willis than stereotactic injection. 72.2% or 82.4% mice which received 2.5 or 5 µL of elastase through CM developed IAs, respectively. Rupture rates were 46.2% and 64.3%, respectively. The aneurysms exhibited histopathological features similar to those of humans, including absence of intimal endothelial cells, degradation of internal elastic lamina, infiltration of inflammatory cells, and loss of vascular smooth muscle cells. CONCLUSION: We propose a mouse model of IA that employs the injection of elastase into CM. The protocol provides a stable and efficient mouse model of ruptured IA.