Evidence map›Paper›PMID 33446503›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

An immunohistochemical study of lymphatic elements in the human brain.

Éva Mezey, Ildikó Szalayova, Christopher T Hogden, Alexandra Brady, Ágnes Dósa, Péter Sótonyi, Miklós Palkovits

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 66 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Éva MezeyAdult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892; mezeye@mail.nih.gov.ORCID 0000-0002-5907-4691
Ildikó SzalayovaAdult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892.ORCID 0000-0002-6857-2297
Christopher T HogdenAdult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892.
Alexandra BradyAdult Stem Cell Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892.
Ágnes DósaDepartment of Forensic Sciences, Semmelweis University, H-1091 Budapest, Hungary.ORCID 0000-0002-8525-4098
Péter SótonyiDepartment of Forensic Sciences, Semmelweis University, H-1091 Budapest, Hungary.
Miklós PalkovitsHuman Brain Tissue Bank, Semmelweis University, H-1094 Budapest, Hungary.ORCID 0000-0003-0578-0387
National Institutes of Health · USSemmelweis University · HU

Funding

Contribution of bone marrow cells to tissue regeneration, immune function and hematopoiesisZIADE000714 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MEZEY, EVA M. · 2009 to 2025
$25.3M
Lymphatic endothelial marker positive cells in the mouse and human nervous systemZIADE000755 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI MEZEY, EVA M. · 2020 to 2025
$1.4M
Intramural NIH HHS ZIA DE000714
6 · The paper itself

Abstract

Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) "glymphatics," but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs were present in the perivascular space, the walls of small and large arteries and veins, the media of large vessels along smooth muscle cell membranes, and the vascular adventitia. Lymphatic marker staining was detected in the pia mater, in the arachnoid, in venous sinuses, and among the layers of the dura mater. There were many LMPCs in the perineurium and endoneurium of cranial nerves. Soluble waste may move from the brain parenchyma via perivascular and paravascular routes to the closest subarachnoid space and then travel along the dura mater and/or cranial nerves. Particulate waste products travel along the laminae of the dura mater toward the jugular fossa, lamina cribrosa, and perineurium of the cranial nerves to enter the cervical lymphatics. CD3-positive T cells appear to be in close proximity to LMPCs in perivascular/perineural spaces throughout the brain. Both immunostaining and qPCR confirmed the presence of adhesion molecules in the CNS known to be involved in T cell migration.

Indexed as

AgedAged, 80 and overAntibodiesAutopsyBrainCell MovementCentral Nervous SystemDura MaterEndothelium, LymphaticFemaleGlymphatic SystemHumansImmunohistochemistryLymphatic SystemLymphatic VesselsMaleAntibodiesFLT4 protein, humanLYVE1 protein, humanMembrane GlycoproteinsPDPN protein, humanPodoplaninVascular Endothelial Growth Factor Receptor-3Vesicular Transport Proteinscranial nervesCSFmeningespodoplaninT cells

Identifiers

PMID33446503
PMCPMC7826383
OpenAlexW3119445233

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.