Perivascular spaces, glymphatic dysfunction, and small vessel disease
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 discovere...
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| Published in | Clinical science (1979) Vol. 131; no. 17; pp. 2257 - 2274 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
01.09.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0143-5221 1470-8736 1470-8736 |
| DOI | 10.1042/CS20160381 |
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| 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. |
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| AbstractList | 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. Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces 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, 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. 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.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. |
| Author | Nedergaard, Maiken Mestre, Humberto Mehta, Rupal I. Kostrikov, Serhii |
| AuthorAffiliation | 2 Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA 4 Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, NY 14642, USA 3 Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA 5 Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark 1 Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA |
| AuthorAffiliation_xml | – name: 4 Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, NY 14642, USA – name: 1 Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA – name: 3 Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA – name: 2 Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA – name: 5 Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark |
| Author_xml | – sequence: 1 givenname: Humberto surname: Mestre fullname: Mestre, Humberto organization: Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A – sequence: 2 givenname: Serhii surname: Kostrikov fullname: Kostrikov, Serhii organization: Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark – sequence: 3 givenname: Rupal I. surname: Mehta fullname: Mehta, Rupal I. organization: Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, NY 14642, U.S.A – sequence: 4 givenname: Maiken surname: Nedergaard fullname: Nedergaard, Maiken organization: Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, U.S.A., Center for Basic and Translational Neuroscience, University of Copenhagen, Copenhagen, Denmark |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28798076$$D View this record in MEDLINE/PubMed |
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| ISSN | 0143-5221 1470-8736 |
| IngestDate | Thu Aug 21 18:19:04 EDT 2025 Fri Jul 11 11:53:57 EDT 2025 Thu Jan 02 23:11:55 EST 2025 Tue Jul 01 01:19:42 EDT 2025 Thu Apr 24 23:02:11 EDT 2025 |
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| Issue | 17 |
| Keywords | CNS clearance Cerebrospinal fluid Small vessel disease Perivascular space Glymphatic |
| Language | English |
| License | 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 These authors contributed equally to this work. |
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| PublicationYear | 2017 |
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| Snippet | Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular... Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular... |
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| SubjectTerms | Animals Aquaporin 4 - genetics Aquaporin 4 - metabolism Blood Vessels - metabolism Blood Vessels - physiopathology Brain - metabolism Brain - physiopathology Cerebral Small Vessel Diseases - metabolism Cerebral Small Vessel Diseases - physiopathology Humans |
| Title | Perivascular spaces, glymphatic dysfunction, and small vessel disease |
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