Evidence map›Paper›PMID 30734065›Full record

ArticleCellular and molecular life sciences : CMLS2019

Tight junction proteins at the blood-brain barrier: far more than claudin-5.

Philipp Berndt, Lars Winkler, Jimmi Cording, Olga Breitkreuz-Korff, André Rex, Sophie Dithmer, Valentina Rausch, Rosel Blasig, Matthias Richter, Anje Sporbert and 3 more

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

141 citing papers in PubMed, 247 citations in OpenAlex.

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81 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 1 country.

Philipp BerndtLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Lars WinklerLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany. winkler@fmp-berlin.de.
Jimmi CordingLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Olga Breitkreuz-KorffLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
André RexDepartment of Experimental Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Sophie DithmerLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Valentina RauschLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Rosel BlasigLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Matthias RichterMax-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Anje SporbertMax-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Hartwig WolburgInstitut für Pathologie und Neuropathologie, Universität Tübingen, Liebermeisterstraße 8, 72076, Tübingen, Germany.
Ingolf E BlasigLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Reiner F HaseloffLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany. haseloff@fmp-berlin.de.ORCID http://orcid.org/0000-0001-9005-5993
Leibniz-Forschungsinstitut für Molekulare Pharmakologie · DEMax Delbrück Center · DECharité - Universitätsmedizin Berlin · DEUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

At the blood-brain barrier (BBB), claudin (Cldn)-5 is thought to be the dominant tight junction (TJ) protein, with minor contributions from Cldn3 and -12, and occludin. However, the BBB appears ultrastructurally normal in Cldn5 knock-out mice, suggesting that further Cldns and/or TJ-associated marvel proteins (TAMPs) are involved. Microdissected human and murine brain capillaries, quickly frozen to recapitulate the in vivo situation, showed high transcript expression of Cldn5, -11, -12, and -25, and occludin, but also abundant levels of Cldn1 and -27 in man. Protein levels were quantified by a novel epitope dilution assay and confirmed the respective mRNA data. In contrast to the in vivo situation, Cldn5 dominates BBB expression in vitro, since all other TJ proteins are at comparably low levels or are not expressed. Cldn11 was highly abundant in vivo and contributed to paracellular tightness by homophilic oligomerization, but almost disappeared in vitro. Cldn25, also found at high levels, neither tightened the paracellular barrier nor interconnected opposing cells, but contributed to proper TJ strand morphology. Pathological conditions (in vivo ischemia and in vitro hypoxia) down-regulated Cldn1, -3, and -12, and occludin in cerebral capillaries, which was paralleled by up-regulation of Cldn5 after middle cerebral artery occlusion in rats. Cldn1 expression increased after Cldn5 knock-down. In conclusion, this complete Cldn/TAMP profile demonstrates the presence of up to a dozen TJ proteins in brain capillaries. Mouse and human share a similar and complex TJ profile in vivo, but this complexity is widely lost under in vitro conditions.

Indexed as

Blood-Brain BarrierAdultAnimalsBrainCells, CulturedClaudin-5FemaleGene ExpressionHEK293 CellsHumansMaleMice, Inbred C57BLMice, KnockoutMice, TransgenicMiddle AgedProtein IsoformsClaudin-5Protein IsoformsTight Junction ProteinsBrain endotheliumIschemiaLaser capture microdissectionNeurovasculatureProtein–protein interaction

Identifiers

PMID30734065
PMCPMC11105330
OpenAlexW2913231079

What OpenQuestion holds

Textmetadata
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.