Arterial pulsations drive oscillatory flow of CSF but not directional pumping

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Abstract

The brain lacks a traditional lymphatic system for metabolite clearance. The existence of a “glymphatic system” where metabolites are removed from the brain’s extracellular space by convective exchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) along the paravascular spaces (PVS) around cerebral blood vessels has been controversial. While recent work has shown clear evidence of directional flow of CSF in the PVS in anesthetized mice, the driving force for the observed fluid flow remains elusive. The heartbeat-driven peristaltic pulsation of arteries has been proposed as a probable driver of directed CSF flow. In this study, we use rigorous fluid dynamic simulations to provide a physical interpretation for peristaltic pumping of fluids. Our simulations match the experimental results and show that arterial pulsations only drive oscillatory motion of CSF in the PVS. The observed directional CSF flow can be explained by naturally occurring and/or experimenter-generated pressure differences.

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Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence

Stephen B Hladky, Margery A Barrand (2014)

Interstitial fluid (ISF) surrounds the parenchymal cells of the brain and spinal cord while cerebrospinal fluid (CSF) fills the larger spaces within and around the CNS. Regulation of the composition and volume of these fluids is important for effective functioning of brain cells and is achieved by barriers that prevent free exchange between CNS and blood and by mechanisms that secrete fluid of controlled composition into the brain and distribute and reabsorb it. Structures associated with this regular fluid turnover include the choroid plexuses, brain capillaries comprising the blood-brain barrier, arachnoid villi and perineural spaces penetrating the cribriform plate. ISF flow, estimated from rates of removal of markers from the brain, has been thought to reflect rates of fluid secretion across the blood-brain barrier, although this has been questioned because measurements were made under barbiturate anaesthesia possibly affecting secretion and flow and because CSF influx to the parenchyma via perivascular routes may deliver fluid independently of blood-brain barrier secretion. Fluid secretion at the blood-brain barrier is provided by specific transporters that generate solute fluxes so creating osmotic gradients that force water to follow. Any flow due to hydrostatic pressures driving water across the barrier soon ceases unless accompanied by solute transport because water movements modify solute concentrations. CSF is thought to be derived primarily from secretion by the choroid plexuses. Flow rates measured using phase contrast magnetic resonance imaging reveal CSF movements to be more rapid and variable than previously supposed, even implying that under some circumstances net flow through the cerebral aqueduct may be reversed with net flow into the third and lateral ventricles. Such reversed flow requires there to be alternative sites for both generation and removal of CSF. Fluorescent tracer analysis has shown that fluid flow can occur from CSF into parenchyma along periarterial spaces. Whether this represents net fluid flow and whether there is subsequent flow through the interstitium and net flow out of the cortex via perivenous routes, described as glymphatic circulation, remains to be established. Modern techniques have revealed complex fluid movements within the brain. This review provides a critical evaluation of the data.

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Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology.

N. Abbott (2004)

This review surveys evidence for the flow of brain interstitial fluid (ISF) via preferential pathways through the brain, and its relation to cerebrospinal fluid (CSF). Studies over >100 years have raised several controversial points, not all of them resolved. Recent studies have usefully combined a histological and a mathematical approach. Taken together the evidence indicates an ISF bulk flow rate of 0.1-0.3 microl min(-1) g(-1) in rat brain along preferential pathways especially perivascular spaces and axon tracts. The main source of this fluid is likely to be the brain capillary endothelium, which has the necessary ion transporters, channels and water permeability to generate fluid at a low rate, c1/100th of the rate per square centimeter of CSF secretion across choroid plexus epithelium. There is also evidence that a proportion of CSF may recycle from the subarachnoid space into arterial perivascular spaces on the ventral surface of the brain, and join the circulating ISF, draining back via venous perivascular spaces and axon tracts into CSF compartments, and out both through arachnoid granulations and along cranial nerves to the lymphatics of the neck. The bulk flow of ISF has implications for non-synaptic cell:cell communication (volume transmission); for drug delivery, distribution, and clearance; for brain ionic homeostasis and its disturbance in brain edema; for the immune function of the brain; for the clearance of beta-amyloid deposits; and for the migration of cells (malignant cells, stem cells). Copyright 2003 Elsevier Ltd.

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Aquaporin water channels--from atomic structure to clinical medicine.

Peter Agre, Landon King, Masato Yasui … (2002)

The water permeability of biological membranes has been a longstanding problem in physiology, but the proteins responsible for this remained unknown until discovery of the aquaporin 1 (AQP1) water channel protein. AQP1 is selectively permeated by water driven by osmotic gradients. The atomic structure of human AQP1 has recently been defined. Each subunit of the tetramer contains an individual aqueous pore that permits single-file passage of water molecules but interrupts the hydrogen bonding needed for passage of protons. At least 10 mammalian aquaporins have been identified, and these are selectively permeated by water (aquaporins) or water plus glycerol (aquaglyceroporins). The sites of expression coincide closely with the clinical phenotypes--ranging from congenital cataracts to nephrogenic diabetes insipidus. More than 200 members of the aquaporin family have been found in plants, microbials, invertebrates and vertebrates, and their importance to the physiology of these organisms is being uncovered.

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Author and article information

Contributors

Francesco Costanzo: fxc8@psu.edu

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 22 June 2020

Publication date PMC-release: 22 June 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 10102

Affiliations

[1 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Department of Engineering Science and Mechanics, The Pennsylvania State University, ; University Park, PA United States

[2 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Center for Neural Engineering, The Pennsylvania State University, ; University Park, PA United States

[3 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Department of Biomedical Engineering, The Pennsylvania State University, ; University Park, PA United States

[4 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Department of Neurosurgery, The Pennsylvania State University, ; University Park, PA United States

[5 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Department of Mathematics, The Pennsylvania State University, ; University Park, PA United States

Article

Publisher ID: 66887

DOI: 10.1038/s41598-020-66887-w

PMC ID: 7308311

PubMed ID: 32572120

SO-VID: 331fa6d7-6952-448b-810c-03a2381622d8

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 13 March 2020

Date accepted : 28 May 2020

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ScienceOpen disciplines: Uncategorized

Keywords: computational biophysics,permeation and transport,biomedical engineering

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ScienceOpen disciplines: Uncategorized

Keywords: computational biophysics, permeation and transport, biomedical engineering

Arterial pulsations drive oscillatory flow of CSF but not directional pumping

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Most cited references 46

Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence

Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology.

Aquaporin water channels--from atomic structure to clinical medicine.

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