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Cardiovasc Res. 2018 Sep 1;114(11):1462-1473. doi: 10.1093/cvr/cvy113.

Understanding the role of the perivascular space in cerebral small vessel disease.

Author information

1
Centre for Clinical Brain Sciences, The University of Edinburgh, Chancellor's Building, Edinburgh, UK.
2
Department of Anesthesiology, Yale School of Medicine, New Haven, USA.
3
LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
4
Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
5
Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Canada.
6
Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
7
INSERM U1128, Laboratory of Neurophysiology and New Microscopies, Université Paris Descartes, Paris, France.
8
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
9
German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.
10
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
11
Genetics and Pathogenesis of Cerebrovascular Diseases, INSERM, Université Paris Diderot-Paris 7, Paris, France.
12
DHU NeuroVasc, Sorbonne Paris Cité, Paris, France.
13
Section for Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
14
Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, USA.
15
Department of Neuroinflammation, UCL Institute of Neurology, London, UK.
16
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, USA.
17
Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, USA.
18
Centre for Clinical Brain Sciences, Chancellor's Building, Edinburgh, UK.
19
UK Dementia Research Institute at The University of Edinburgh, Chancellor's Building, Edinburgh, UK.
20
Row Fogo Centre for Research into Ageing and the Brain, The University of Edinburgh, Chancellor's Building, Edinburgh, UK.

Abstract

Small vessel diseases (SVDs) are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD. In healthy tissue, these spaces are proposed to form part of a complex brain fluid drainage system which supports interstitial fluid exchange and may also facilitate clearance of waste products from the brain. The pathophysiological signature of PVS and what this infers about their function and interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development in the brain has not been established. Here we discuss the potential of enlarged PVS to be a unique biomarker for SVD and related brain disorders with a vascular component. We propose that widening of PVS suggests presence of peri-vascular cell debris and other waste products that form part of a vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid space, leading to accumulation of toxins, hypoxia, and tissue damage. Here, we outline current knowledge, questions and hypotheses regarding understanding the brain fluid dynamics underpinning dementia and stroke through the common denominator of SVD.

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