Abstract TP124: Development of a Novel Mouse Surgical Model for Moyamoya Syndrome

Abstract

Introduction: Moyamoya is characterized by progressive stenosis and occlusion of the intracranial internal carotid arteries (ICA) and their major branches. Vascular stenosis is accompanied by formation of abnormal vascular networks, with major symptoms including ischemia and hemorrhage. Current treatments are limited to antiplatelet therapy and surgical bypass. While research has recently discovered a susceptibility gene (RNF213) for idiopathic moyamoya disease, there is still no animal model which mimics the acquired vasculopathy of moyamoya syndrome, which is often associated with autoimmune diseases. We report here a novel surgical model of moyamoya that employs microcoils placed on the ICA of mice. Methods: Male C57Bl/6 mice (4 months old) underwent surgery for the unilateral placement of a microcoil (0.16 mm) onto the proximal ICA, referred to as internal carotid artery stenosis (ICAS). After 28 days, the blood vessels were examined for changes in diameter and number of anastomoses using a fluorescent dye called Di I. Cresyl violet and Prussian blue were used to assess ischemia and hemorrhage, while PCR was used to examine biomarkers typically altered in moyamoya patients. Results: We observed a significant narrowing of the distal ICA and anterior cerebral artery (ACA) in the Circle of Willis, as well as a decreased number of anastomoses between the middle cerebral artery (MCA) and the ACA in the watershed region of the cortex in ICAS-treated mice. Histological examination also showed changes in brain cellular morphology and alterations in VEGF and MMP9 gene expression. Conclusions: We report for the first time the development of an animal model with moyamoya-like vasculopathies as observed in humans. While further characterization is needed, it may provide a crucial model for development of therapies for moyamoya syndrome.