Perivascular spaces, glymphatic dysfunction, and small vessel disease

TY - JOUR

T1 - Perivascular spaces, glymphatic dysfunction, and small vessel disease

AU - Mestre, Humberto

AU - Kostrikov, Serhii

AU - Mehta, Rupal I.

AU - Nedergaard, Maiken

N1 - © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - Animals

KW - Aquaporin 4

KW - Blood Vessels

KW - Brain

KW - Cerebral Small Vessel Diseases

KW - Humans

KW - Journal Article

KW - Review

U2 - 10.1042/CS20160381

DO - 10.1042/CS20160381

M3 - Review

C2 - 28798076

SN - 0143-5221

VL - 131

SP - 2257

EP - 2274

JO - Clinical Science

JF - Clinical Science

IS - 17

ER -