Evidence map›Paper›PMID 33711041›Full record

ArticlePloS one2021

The blood-brain barrier studied in vitro across species.

Maj Schneider Thomsen, Nanna Humle, Eva Hede, Torben Moos, Annette Burkhart, Louiza Bohn Thomsen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.1field-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

44 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Comparative analysis of the uptake of the HFluids and barriers of the CNS · 2025
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. 3DFrontiers in pharmacology · 2025
    Review
  19. Article
  20. Article
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

6 authors at 1 institution in 1 country.

Maj Schneider ThomsenDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.
Nanna HumleDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.
Eva HedeDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.
Torben MoosDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.ORCID 0000-0001-9989-0207
Annette BurkhartDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.ORCID 0000-0003-2086-4693
Louiza Bohn ThomsenDepartment of Health Science and Technology, Neurobiology Research and Drug Delivery, Aalborg University, Aalborg, Denmark.
Aalborg University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (BECs) supported by pericytes and astrocytes. The BBB maintains homeostasis and protects the brain against toxic substances circulating in the blood, meaning that only a few drugs can pass the BBB. Thus, for drug screening, understanding cell interactions, and pathology, in vitro BBB models have been developed using BECs from various animal sources. When comparing models of different species, differences exist especially in regards to the transendothelial electrical resistance (TEER). Thus, we compared primary mice, rat, and porcine BECs (mBECs, rBECs, and pBECs) cultured in mono- and co-culture with astrocytes, to identify species-dependent differences that could explain the variations in TEER and aid to the selection of models for future BBB studies. The BBB models based on primary mBECs, rBECs, and pBECs were evaluated and compared in regards to major BBB characteristics. The barrier integrity was evaluated by the expression of tight junction proteins and measurements of TEER and apparent permeability (Papp). Additionally, the cell size, the functionality of the P-glycoprotein (P-gp) efflux transporter, and the expression of the transferrin receptor were evaluated and compared. Expression and organization of tight junction proteins were in all three species influenced by co-culturing, supporting the findings, that TEER increases after co-culturing with astrocytes. All models had functional polarised P-gp efflux transporters and expressed the transferrin receptor. The most interesting discovery was that even though the pBECs had higher TEER than rBECs and mBECs, the Papp did not show the same variation between species, which could be explained by a significantly larger cell size of pBECs. In conclusion, our results imply that the choice of species for a given BBB study should be defined from its purpose, instead of aiming to reach the highest TEER, as the models studied here revealed similar BBB properties.

Indexed as

AnimalsAstrocytesATP Binding Cassette Transporter, Subfamily BBlood-Brain BarrierCell Culture TechniquesCells, CulturedCell SizeEndothelial CellsMiceModels, BiologicalPermeabilityRatsReceptors, TransferrinSwineTight Junction ProteinsATP Binding Cassette Transporter, Subfamily BReceptors, TransferrinTight Junction Proteins

Identifiers

PMID33711041
PMCPMC7954348
OpenAlexW3134296362

What OpenQuestion holds

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LicenceCC BY
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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.