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Cited by 206Barrier Structure and Function StudiesCerebrospinal fluid and hydrocephalusDrug Transport and Resistance Mechanisms

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

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Hladky, Stephen B., Barrand, Margery A.·2018·Fluids and Barriers of the CNS
DOI 10.1186/s12987-018-0113-6PMC PMC6194691
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Abstract

This review considers efflux of substances from brain parenchyma quantified as values of clearances (CL, stated in µL g -1 min -1 ).Total clearance of a substance is the sum of clearance values for all available routes including perivascular pathways and the blood-brain barrier.Perivascular efflux contributes to the clearance of all water-soluble substances.Substances leaving via the perivascular routes may enter cerebrospinal fluid (CSF) or lymph.These routes are also involved in entry to the parenchyma from CSF.However, evidence demonstrating net fluid flow inwards along arteries and then outwards along veins (the glymphatic hypothesis) is still lacking.CL perivascular , that via perivascular routes, has been measured by following the fate of exogenously applied labelled tracer amounts of sucrose, inulin or serum albumin, which are not metabolized or eliminated across the blood-brain barrier.With these substances values of total CL ≅ 1 have been measured.Substances that are eliminated at least partly by other routes, i.e. across the blood-brain barrier, have higher total CL values.Substances crossing the blood-brain barrier may do so by passive, non-specific means with CL blood-brain barrier values ranging from < 0.01 for inulin to > 1000 for water and CO 2 .CL blood-brain barrier values for many small solutes are predictable from their oil/water partition and molecular weight.Transporters specific for glucose, lactate and many polar substrates facilitate efflux across the blood-brain barrier producing CL blood-brain barrier values > 50.The principal route for movement of Na + and Cl -ions across the blood-brain barrier is probably paracellular through tight junctions between the brain endothelial cells producing CL blood-brain barrier values ~ 1.There are large fluxes of amino acids into and out of the brain across the blood-brain barrier but only small net fluxes have been observed suggesting substantial reuse of essential amino acids and α-ketoacids within the brain.Amyloid-β efflux, which is measurably faster than efflux of inulin, is primarily across the blood-brain barrier.Amyloid-β also leaves the brain parenchyma via perivascular efflux and this may be important as the route by which amyloid-β reaches arterial walls resulting in cerebral amyloid angiopathy.

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  • Passive transcytosis has two possible routes across the microvascular endothelial layer: paracellular and transcellular.

    “Passive transcytosis, also known as non-specific transfers, has two possible routes across the microvascular endothelial layer, via paracellular and transcellular.147”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [147]

    The ‘Passive, non-specific transfer across the blood–brain barrier’ section states that passive transfer has two routes through or around microvascular endothelial cells. But the separate ‘Efflux by transcytosis’ section describes transcytosis as vesicular transfer through endothelial cells, not as a name for passive transfer by both routes. (LLM, conf=0.88)

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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
2018-10-19
Volume
15
Issue
1
Pages
30-30
ISSN
2045-8118 (ISSN-L)
DOI
10.1186/s12987-018-0113-6
PMC
PMC6194691
OpenAlex
W2896062620
Cited by
206
References
59
Citations by year
2026: 14 · 2025: 26 · 2024: 23 · 2023: 40 · 2022: 32 · 2021: 29 · 2020: 18 · 2019: 22 · 2018: 1 · 2017: 1
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Fluids and Barriers of the CNS (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
blood-brain barrier, glymphatic system, cerebrospinal fluid, lymphatic drainage, cerebral amyloid angiopathy, amino acid transport, ion transport
MeSH terms
Parenchymal Tissue, Glymphatic System, Animals, Blood-Brain Barrier, Brain, Humans, Models, Neurological, Membrane Transport Proteins

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