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Clin Sci (Lond). 2017 Aug 10;131(17):2257-2274. doi: 10.1042/CS20160381. Print 2017 Sep 1.

Perivascular spaces, glymphatic dysfunction, and small vessel disease.

Author information

1
Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
2
Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
3
Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark.
4
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
5
Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, NY 14642, U.S.A.
6
Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A. maiken_nedergaard@urmc.rochester.edu.

Abstract

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.

KEYWORDS:

CNS clearance; Cerebrospinal fluid; Glymphatic; Perivascular space; Small vessel disease

PMID:
28798076
PMCID:
PMC5567781
DOI:
10.1042/CS20160381
[Indexed for MEDLINE]
Free PMC Article

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