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

Brown, R; Benveniste, H; Black, SE; Charpak, S; Dichgans, M; Joutel, A; Nedergaard, M; ... Wardlaw, JM; + view all (2018) Understanding the role of the perivascular space in cerebral small vessel disease. Cardiovascular Research 10.1093/cvr/cvy113. (In press). Green open access

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Abstract

Small vessel diseases 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 (MRI) 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 forms part of a vicious cycle involving impaired cerebrovascular reactivity (CVR), blood-brain barrier (BBB) dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid (ISF) 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.

Type: Article
Title: Understanding the role of the perivascular space in cerebral small vessel disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cvr/cvy113
Publisher version: https://doi.org/10.1093/cvr/cvy113
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: stroke, cerebrovascular, dementia, small vessel disease, perivascular space
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10049721
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