CoChat
Sign Up
Cited by 66Neuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function StudiesThermal Regulation in Medicine

Glial functions in the blood-brain communication at the circumventricular organs

Open access
Miyata, Seiji·2022·Frontiers in Neuroscience
DOI 10.3389/fnins.2022.991779PMC PMC9583022
Open this paper in CoChat — free accountOpen PDF

Abstract

The circumventricular organs (CVOs) are located around the brain ventricles, lack a blood-brain barrier (BBB) and sense blood-derived molecules. This review discusses recent advances in the importance of CVO functions, especially glial cells transferring periphery inflammation signals to the brain. The CVOs show size-limited vascular permeability, allowing the passage of molecules with molecular weight <10,000. This indicates that the lack of an endothelial cell barrier does not mean the free movement of blood-derived molecules into the CVO parenchyma. Astrocytes and tanycytes constitute a dense barrier at the distal CVO subdivision, preventing the free diffusion of blood-derived molecules into neighboring brain regions. Tanycytes in the CVOs mediate communication between cerebrospinal fluid and brain parenchyma via transcytosis. Microglia and macrophages of the CVOs are essential for transmitting peripheral information to other brain regions via toll-like receptor 2 (TLR2). Inhibition of TLR2 signaling or depletion of microglia and macrophages in the brain eliminates TLR2-dependent inflammatory responses. In contrast to TLR2, astrocytes and tanycytes in the CVOs of the brain are crucial for initiating lipopolysaccharide (LPS)-induced inflammatory responses via TLR4. Depletion of microglia and macrophages augments LPS-induced fever and chronic sickness responses. Microglia and macrophages in the CVOs are continuously activated, even under normal physiological conditions, as they exhibit activated morphology and express the M1/M2 marker proteins. Moreover, the microglial proliferation occurs in various regions, such as the hypothalamus, medulla oblongata, and telencephalon, with a marked increase in the CVOs, due to low-dose LPS administration, and after high-dose LPS administration, proliferation is seen in most brain regions, except for the cerebral cortex and hippocampus. A transient increase in the microglial population is beneficial during LPS-induced inflammation for attenuating sickness response. Transient receptor potential receptor vanilloid 1 expressed in astrocytes and tanycytes of the CVOs is responsible for thermoregulation upon exposure to a warm environment less than 37°C. Alternatively, Na x expressed in astrocytes and tanycytes of the CVOs is crucial for maintaining body fluid homeostasis. Thus, recent findings indicate that glial cells in the brain CVOs are essential for initiating neuroinflammatory responses and maintaining body fluid and thermal homeostasis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnins.2022.991779

Cites

223 of 223 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Circumventricular organs (CVOs) are specialized structures located around the third and fourth ventricles that mediate communications between brain, blood and cerebrospinal fluid (CSF).

    “Circumventricular organs (CVOs) are specialized structures located around the third and fourth ventricles that mediate communications between brain, blood and cerebrospinal fluid74,75 (CSF).”

    From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [75]

    The General introduction says CVOs lie around the brain ventricles and transmit blood-derived information to brain regions. The Abstract and the section on tanycytic transcytosis describe communication between CSF and brain parenchyma. Our copy does not specifically locate CVOs around the third and fourth ventricles, so that more precise part of the claim is not supported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 224 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Ehrlich R. H. (1885). Das Sauerstoff-Bedurfinis dews Oraganisms. Eine Farenanalytisch Studie. Ph.D. Thesis. Berlin: Herschwarld, 69– 72.

Cited by

Sorted by citations

Related

Authors
Miyata, S.
Affiliations
Kyoto Institute of Technology (JP)
Corresponding author
Miyata, Seiji
ORCID
Miyata, Seiji
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2022-10-06
Volume
16
Pages
991779-991779
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2022.991779
PMC
PMC9583022
OpenAlex
W4302305006
Cited by
66
References
224
Citations by year
2026: 24 · 2025: 22 · 2024: 13 · 2023: 7
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Japan Society for the Promotion of Science (22K06456, 19K06921)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
Keywords
circumventricular organs, blood-brain barrier, glial cells, tanycytes, astrocytes, microglia, macrophages, TLR2, TLR4, lipopolysaccharide, neuroinflammation, sickness behavior, fever, microglial proliferation, TRPV1, Na+/Ca2+ exchanger, thermoregulation, fluid homeostasis, transcytosis, cerebrospinal fluid, hypothalamus, medulla oblongata

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review