Abstract

Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries. There are two forms: Disease and Syndrome, with each characterized by the sub-population it affects. Moyamoya syndrome (MMS) is more prominent in adults in their 20’s-40’s, and is often associated with autoimmune diseases. Currently, there are no surgical models for inducing moyamoya syndrome, so our aim was to develop a new animal model to study this relatively unknown cerebrovascular disease. Here, we demonstrate a new surgical technique termed internal carotid artery stenosis (ICAS), to mimic MMS using micro-coils on the proximal ICA. We tested for Moyamoya-like vasculopathies by fluorescently labelling the mouse cerebrovasculature with Di I for visualization and analysis of vessel diameter at the distal ICA and anastomoses on the cortical surface. Results show a significant narrowing of the distal ICA and anterior cerebral artery (ACA) in the Circle of Willis, as observed in humans. There is also a significant decrease in the number of anastomoses between the middle cerebral artery (MCA) and the ACA in the watershed region of the cortex. While further characterization is needed, this ICAS model can be applied to transgenic mice displaying co-morbidities as observed within the Moyamoya syndrome population, allowing a better understanding of the disease and development of novel treatments.

Highlights

  • Moyamoya is an occlusive cerebrovascular disorder first reported in 1957 in Japan, and is characterized by stenosis of the supraclinoid portion of the internal carotid arteries (ICA) with the formation of an abnormal vascular network at the base of the brain [1]

  • Diameters of the ICA, anterior cerebral artery (ACA) and middle cerebral artery (MCA) vessels were examined by measuring the width of each vessel near the bifurcation point on both the ipsilateral and contralateral sides to determine if there was any difference between internal carotid artery stenosis (ICAS) and control groups (Fig 2A)

  • To determine whether cerebrovascular changes induced by ICAS might mimic human Moyamoya syndrome (MMS), we qualitatively compared our ICA, ACA, and MCA vessel diameter measurement results to that seen in clinical MMS

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Summary

Introduction

Moyamoya is an occlusive cerebrovascular disorder first reported in 1957 in Japan, and is characterized by stenosis of the supraclinoid portion of the internal carotid arteries (ICA) with the formation of an abnormal vascular network at the base of the brain [1]. New mouse surgical model for moyamoya moyamoya syndrome (MMS), which is idiopathic, and typically seen among Caucasian adults ranging in age from 20 to 40 years. Clinical course for both may be unilateral or bilateral with predisposition to both ischemic and hemorrhagic strokes. While there is no known genetic component in MMS, as there is in MMD, it is often associated with autoimmune disorders such as diabetes, lupus or rheumatoid arthritis [3]. Treatment options for both MMD and MMS involve daily aspirin use, lifestyle modifications to maximize cerebral perfusion, and surgical direct or indirect bypass to restore blood flow

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