A Modified Mouse Model of Intracranial Aneurysm Based on Hemodynamic Change and Hypertension.

Abstract

Intracranial aneurysm (IA) poses a significant health risk due to morbidity and mortality associated with aneurysm rupture. However, the molecular mechanisms underlying IA development remain unclear, and a suitable mouse model is required. A mouse model of IA was established by ligating the pterygopalatine artery (PPA) to induce additive hemodynamic changes, combined with hypertension induction. In C57BL/6 male mice, vessels, including the right PPA, external carotid artery (ECA), occipital artery (OcA), and the left contralateral common carotid artery (CCA), were ligated to induce hemodynamic changes. One week later, the bilateral posterior branches of the renal artery (pRA) were ligated, and an 8% salt diet was introduced to induce hypertension. Magnetic resonance angiography (MRA), stereomicroscopy, and immunohistochemical (IHC) staining were performed to evaluate the morphological and pathological changes in IA three months after induction. In the experimental group, four mice died after the initial induction. IA at different locations was detected in five of the eleven remaining mice. Both microscopic and MRA examinations confirmed IA formation. Pathological and IHC analyses revealed disruption of the internal elastic lamina, disconnection of collagen fibers, and infiltration of CD86-positive M1 macrophages, findings consistent with those observed in human IA. This mouse model of IA replicates the pathological changes observed in human samples and may serve as a valuable tool for investigating the molecular mechanisms of IA formation and progression.