Abstract WP341: Experimental Internal Carotid Artery Stenosis Models Pathogenic Features of Moyamoya Syndrome

Abstract

Introduction: Moyamoya is an arteriopathy defined by the progressive stenosis of the intracranial internal carotid arteries accompanied by the formation of abnormal vascular networks. To address the paucity of research on the adult-onset Moyamoya Syndrome, which completely lacks any animal model for evaluation, our lab created a novel surgical technique, termed internal carotid artery stenosis (ICAS), that attempts to model the cerebrovascular changes seen in the human Moyamoya Syndrome. We hypothesized that the ICAS model would mimic the key proposed pathogenic features of Moyamoya Syndrome; namely, intimal hyperplasia of the major vessels of the cerebrovasculature leading to vessel stenosis and the formation of small, compensatory collateral arteries. Methods: ICAS (n=9) and sham (n=6) surgeries were performed in a randomized fashion on male C57Bl/6 mice (age=16 weeks). Brain tissue sections and RNA were collected 28-days post-surgery. Intimal hyperplasia was assessed with a modified Verhoeff-van Gieson stain. Expression of genes associated with human Moyamoya Syndrome (VEGF, SDF-1α, MMP-9, bFGF, VCAM-1, and MCP-1) was quantified by qPCR. MatLab and PRISM software were used for data analysis. Results: ICAS induces intimal hyperplasia of the cerebrovasculature ( p =0.033). ICAS increases genetic expression of VEGF in the whole brain (fold change=0.60, p =0.050) and SDF-1α in the striatum (fold change=0.59, p =0.016), and decreases genetic expression of MMP-9 in the ipsilateral cortex (fold change=0.39, p =0.044). Furthermore, a trend indicates that ICAS may increase genetic expression of VCAM-1 in the ipsilateral striatum (fold change=0.33, p =0.109). Conclusions: The present finding that ICAS induces intimal hyperplasia and alters genetic expression supports ICAS as a relevant model of the proposed pathology of Moyamoya Syndrome. The upregulation of VEGF, SDF-1α, and VCAM-1 is indicative of angiogenesis, hypoxia-induced vasculogenesis, and ischemia-induced inflammation, while the downregulation of MMP-9 may indicate decreased extracellular remodeling in the cortex. While investigation of the long-term effects of coil-placement is needed, ICAS may provide a crucial model for development of therapies for Moyamoya Syndrome.