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Cited by 636Cerebrospinal fluid and hydrocephalusIon Transport and Channel RegulationBarrier Structure and Function Studies

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

Open access
Hladky, Stephen B, Barrand, Margery A·2014·Fluids and Barriers of the CNS
DOI 10.1186/2045-8118-11-26PMC PMC4326185
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Abstract

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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  • Other recent studies did not support the proposed glymphatic mechanism, nor the convective, pressure-driven fluid flow of cerebrospinal fluid from para-arterial to paravenous spaces throughout the parenchymal extracellular spaces.

    “Other recent studies (252, 255, 547, 555), however, did not support the proposed glymphatic mechanism, nor the convective, pressure-driven fluid flow of CSF from para-arterial to paravenous spaces throughout the parenchymal ECS (31, 30, 255, 296, 547, 255).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [252]

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  1. [147]Fenstermacher J Coxon RV Comment after paper by Katzman Symposium on the Blood-Brain Barrier Wates Foundation; Oxford 1970 Oxford Truex 166

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Authors
Hladky, S. B., & Barrand, M. A.
Affiliations
University of Cambridge (GB)
Corresponding author
Hladky, Stephen B
ORCID
Hladky, Stephen B
Venue
Fluids and Barriers of the CNS
Publisher
Springer Science and Business Media LLC
Published
2014
Volume
11
Issue
1
Pages
26
ISSN
2045-8118 (ISSN-L)
DOI
10.1186/2045-8118-11-26
PMC
PMC4326185
OpenAlex
W2096525076
Cited by
633
References
215
Citations by year
2026: 37 · 2025: 49 · 2024: 57 · 2023: 65 · 2022: 77 · 2021: 75 · 2020: 45 · 2019: 65 · 2018: 61 · 2017: 58 · 2016: 26 · 2015: 17
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Fluids and Barriers of the CNS (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
interstitial fluid, cerebrospinal fluid, cerebrospinal fluid flow, blood-brain barrier, choroid plexus, arachnoid villi, perineural space, cribriform plate, cerebrospinal fluid production, CSF reabsorption, phase-contrast MRI, osmotic gradient, solute transport, perivascular spaces, barbiturate anesthesia

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