TY - JOUR

T1 - Cerebrospinal fluid production by the choroid plexus

T2 - a century of barrier research revisited

AU - MacAulay, Nanna

AU - Keep, Richard F.

AU - Zeuthen, Thomas

PY - 2022

Y1 - 2022

N2 - Cerebrospinal fluid (CSF) envelops the brain and fills the central ventricles. This fluid is continuously replenished by net fluid extraction from the vasculature by the secretory action of the choroid plexus epithelium residing in each of the four ventricles. We have known about these processes for more than a century, and yet the molecular mechanisms supporting this fluid secretion remain unresolved. The choroid plexus epithelium secretes its fluid in the absence of a trans-epithelial osmotic gradient, and, in addition, has an inherent ability to secrete CSF against an osmotic gradient. This paradoxical feature is shared with other 'leaky' epithelia. The assumptions underlying the classical standing gradient hypothesis await experimental support and appear to not suffice as an explanation of CSF secretion. Here, we suggest that the elusive local hyperosmotic compartment resides within the membrane transport proteins themselves. In this manner, the battery of plasma membrane transporters expressed in choroid plexus are proposed to sustain the choroidal CSF secretion independently of the prevailing bulk osmotic gradient.

AB - Cerebrospinal fluid (CSF) envelops the brain and fills the central ventricles. This fluid is continuously replenished by net fluid extraction from the vasculature by the secretory action of the choroid plexus epithelium residing in each of the four ventricles. We have known about these processes for more than a century, and yet the molecular mechanisms supporting this fluid secretion remain unresolved. The choroid plexus epithelium secretes its fluid in the absence of a trans-epithelial osmotic gradient, and, in addition, has an inherent ability to secrete CSF against an osmotic gradient. This paradoxical feature is shared with other 'leaky' epithelia. The assumptions underlying the classical standing gradient hypothesis await experimental support and appear to not suffice as an explanation of CSF secretion. Here, we suggest that the elusive local hyperosmotic compartment resides within the membrane transport proteins themselves. In this manner, the battery of plasma membrane transporters expressed in choroid plexus are proposed to sustain the choroidal CSF secretion independently of the prevailing bulk osmotic gradient.

KW - Cerebrospinal fluid

KW - CSF

KW - Choroid plexus

KW - Blood-CSF-barrier

KW - Osmotic gradients

KW - Membrane transporters

KW - Local osmotic forces

KW - Transporter-mediated water transport

KW - LATERAL INTERCELLULAR SPACES

KW - BLOOD-BRAIN-BARRIER

KW - ACTIVATED ADENOSINE-TRIPHOSPHATASE

KW - VENTRICULAR CELL-MEMBRANE

KW - K-CL COTRANSPORTERS

KW - OSMOTIC WATER-FLOW

KW - NA+-K+-2CL(-) COTRANSPORTER

KW - POTASSIUM-TRANSPORT

KW - INTERSTITIAL FLUID

KW - TIGHT JUNCTION

U2 - 10.1186/s12987-022-00323-1

DO - 10.1186/s12987-022-00323-1

M3 - Review

C2 - 35317823

VL - 19

JO - Fluids and Barriers of the CNS

JF - Fluids and Barriers of the CNS

SN - 2045-8118

IS - 1

M1 - 26

ER -