Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension

• Published in: Nature communications Vol. 9; no. 1; pp. 4878 - 9
• Main Authors: Mestre, Humberto, Tithof, Jeffrey, Du, Ting, Song, Wei, Peng, Weiguo, Sweeney, Amanda M., Olveda, Genaro, Thomas, John H., Nedergaard, Maiken, Kelley, Douglas H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.11.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/69; 59; 631/378; 631/378/2607; 639/766/189; 9/25; Alzheimer's disease; Animals; Arteries - diagnostic imaging; Arteries - physiology; Blood pressure; Brain; Cerebrospinal fluid; Cerebrospinal Fluid - diagnostic imaging; Cerebrospinal Fluid - physiology; Cisterna Magna - anatomy & histology; Cisterna Magna - diagnostic imaging; Cisterna Magna - physiology; Electrocardiography; Experiments; Fixation; Fluid flow; Fluorescent Dyes - chemistry; Glymphatic System - anatomy & histology; Glymphatic System - diagnostic imaging; Glymphatic System - physiology; Heart Rate - physiology; Humanities and Social Sciences; Hypertension; Image Processing, Computer-Assisted; Male; Medical research; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton - instrumentation; Microscopy, Fluorescence, Multiphoton - methods; Microspheres; multidisciplinary; Particle Size; Particle tracking; Particle tracking velocimetry; Perfusion; Pulsatile Flow - physiology; Pulse Wave Analysis - instrumentation; Pulse Wave Analysis - methods; Respiration; Reynolds number; Rheology - instrumentation; Rheology - methods; Science; Science (multidisciplinary); Veins & arteries; Velocity; Velocity measurement
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07318-3

Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance of metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking to quantify CSF flow velocities in PVSs of live mice. CSF flow is pulsatile and driven primarily by the cardiac cycle. The speed of the arterial wall matches that of the CSF, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping. Increasing blood pressure leaves the artery diameter unchanged but changes the pulsations of the arterial wall, increasing backflow and thereby reducing net flow in the PVS. Perfusion-fixation alters the normal flow direction and causes a 10-fold reduction in PVS size. We conclude that particle tracking velocimetry enables the study of CSF flow in unprecedented detail and that studying the PVS in vivo avoids fixation artifacts. Arterial pulsations are thought to drive CSF flow through perivascular spaces (PVSs), but this has never been quantitatively shown. Using particle tracking to quantify CSF flow velocities in PVSs of live mice, the authors show that flow speeds match the instantaneous speeds of the pulsing artery walls that form the inner boundaries of the PVSs.