Year: 2018
Type: review
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.
Source: Cardiovascular Research
DOI: 10.1093/cvr/cvy113
Institutions: University of Edinburgh, Yale University, Sunnybrook Health Science Centre, University of Toronto, Heart and Stroke Foundation, Inserm, Neurophysiologie et nouvelles microscopies, Université Paris Descartes, German Center for Neurodegenerative Diseases, Munich Cluster for Systems Neurology, Institut für Schlaganfall- und Demenzforschung, Ludwig-Maximilians-Universität München, Sorbonne Paris Cité, Université Paris Diderot, University of Copenhagen, University of Rochester Medicine, University of Rochester, UCL Queen Square Institute of Neurology, University College London, University of Southern California, UK Dementia Research Institute
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: UK Dementias Platform, Age and AD related bottlenecks in glymphatic-lymphatic waste transport, G2299739175, Understanding the role of the perivascular space in cerebral small vessel disease, Standards for determining the vascular contribution to neurodegeneration, G4449473775, Glymphatic function in a transgenic rat model of Alzheimer's disease, Capillary hyperemia in white matter: Novel mechanistic insight and effect of hypertension and aging, Para-Vascular Basis of Small Vessel Disease, Vascular Contributions to Dementia and Genetic Risk Factors for Alzheimer's Disease
OpenAlex ID: W2801199684