Understanding the Role of the Perivascular Space in Cerebral Small Vessel Disease

Centre for Clinical Brain Sciences, University of Edinburgh

The Fondation Leducq recently funded an international network for cerebral small vessel disease (SVD) research, in which Edinburgh University is a lead institute. SVD refers to the pathological alteration of the small blood vessels in the brain, including small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia, almost 50% have an SVD component. Furthermore, SVD plays a causative role in a large proportion of strokes (1). The underlying cause of SVD is unknown. Magnetic resonance imaging (MRI) has identified enlarged perivascular spaces (ePVS) as a hallmark feature of SVD (1,2). These spaces form part of the glymphatic fluid system and provide a pathway for clearance of waste products from the brain (3). The aim of this project is to investigate the role of ePVS in SVD, working around the main hypothesis that altered fluid transport is a common pathological feature in neurodegenerative disorders which have a vascular component (4). We propose that fluid stagnation in ePVS is part of a vicious cycle that involves impaired blood-brain barrier function, cerebrovascular reactivity, pulse wave transmission and  inflammation and contributes to  impaired tissue drainage, accumulation of toxins, hypoxia and tissue damage. Our network includes researchers with expertise in the areas essential for studying SVD at the cellular, tissue and patient levels. We will use both established and novel animal models, and a combination of advanced preclinical and clinical imaging techniques to address this question. We are now forming a local SVD research group in Edinburgh, aimed at encouraging collaboration and facilitating interaction between clinical and preclinical groups across the university. We will provide educational information via local talks and on our website. Interested junior researchers are encouraged to contact rosalind.brown@ed.ac.uk

References

1. Wardlaw JM et al. 2013 Lancet Neurol 12(5): 483-97 2. Potter GM et al. 2015 Int J Stroke 10(3):376-81 3. Iliff JJ et al. 2013 J Clin Invest 123(3):1299-1309 4. Ramirez J et al. 2016 Cell Mol Neurobiol 32:289-299

Funded by: the Fondation Leducq Transatlantic Networks of Excellence program