Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces (PVSs), cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered.
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September 2017
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A flurogold labeled-retina flatmount (front) representing surviving retinal ganglion cells, and the chemical structure of trimetazidine (background). In Clinical Science volume 131, issue 18, Wan et al. report that trimetazidine protects retinal ganglion cells against acute glaucoma via the Nrf2/Ho-1 pathway and propose it as a novel therapeutic agent; for details, see pages 2363-2375.
Review Article|
August 10 2017
Perivascular spaces, glymphatic dysfunction, and small vessel disease
Humberto Mestre;
Humberto Mestre
*
1Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
2Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
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Serhii Kostrikov;
Serhii Kostrikov
*
5Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark
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Rupal I. Mehta;
Rupal I. Mehta
1Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
2Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
3Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
4Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
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Maiken Nedergaard
1Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
2Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
5Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark
Correspondence: Maiken Nedergaard ([email protected])
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Publisher: Portland Press Ltd
Received:
March 17 2017
Revision Received:
July 09 2017
Accepted:
July 24 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (17): 2257–2274.
Article history
Received:
March 17 2017
Revision Received:
July 09 2017
Accepted:
July 24 2017
Citation
Humberto Mestre, Serhii Kostrikov, Rupal I. Mehta, Maiken Nedergaard; Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci (Lond) 1 September 2017; 131 (17): 2257–2274. doi: https://doi.org/10.1042/CS20160381
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