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

TY - JOUR

T1 - Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension

AU - Mestre, Humberto

AU - Tithof, Jeffrey

AU - Du, Ting

AU - Song, Wei

AU - Peng, Weiguo

AU - Sweeney, Amanda M.

AU - Olveda, Genaro

AU - Thomas, John H.

AU - Nedergaard, Maiken

AU - Kelley, Douglas H.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-07318-3

DO - 10.1038/s41467-018-07318-3

M3 - Journal article

C2 - 30451853

AN - SCOPUS:85056707037

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4878

ER -