Evidence map›Paper›PMID 22894547›Full record

ArticleBMC neuroscience2012

In vivo assessment of the permeability of the blood-brain barrier and blood-retinal barrier to fluorescent indoline derivatives in zebrafish.

Kohei Watanabe, Yuhei Nishimura, Tsuyoshi Nomoto, Noriko Umemoto, Zi Zhang, Beibei Zhang, Junya Kuroyanagi, Yasuhito Shimada, Taichi Shintou, Mie Okano and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. A novel class of indole derivatives: enhanced bioavailability, permeability, and antioxidant efficacy for thromboembolic disease therapy.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024
    Article
  5. Review
  6. Article
  7. Toxicity of Jegosaponins A and B fromInternational journal of molecular sciences · 2021
    Article
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  9. Article
  10. Article
  11. Article
  12. Article
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  14. Review
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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

13 authors at 2 institutions in 1 country.

Kohei WatanabeCorporate R&D Headquarters, Canon Inc Tokyo, Ohta-ku, Japan.
Yuhei Nishimura
Tsuyoshi Nomoto
Noriko Umemoto
Zi Zhang
Beibei Zhang
Junya Kuroyanagi
Yasuhito Shimada
Taichi Shintou
Mie Okano
Takeshi Miyazaki
Takeshi Imamura
Toshio Tanaka
Mie University · JPCanon (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSuccessful delivery of compounds to the brain and retina is a challenge in the development of therapeutic drugs and imaging agents. This challenge arises because internalization of compounds into the brain and retina is restricted by the blood-brain barrier (BBB) and blood-retinal barrier (BRB), respectively. Simple and reliable in vivo assays are necessary to identify compounds that can easily cross the BBB and BRB.

methodsWe developed six fluorescent indoline derivatives (IDs) and examined their ability to cross the BBB and BRB in zebrafish by in vivo fluorescence imaging. These fluorescent IDs were administered to live zebrafish by immersing the zebrafish larvae at 7-8 days post fertilization in medium containing the ID, or by intracardiac injection. We also examined the effect of multidrug resistance proteins (MRPs) on the permeability of the BBB and BRB to the ID using MK571, a selective inhibitor of MRPs.

resultsThe permeability of these barriers to fluorescent IDs administered by simple immersion was comparable to when administered by intracardiac injection. Thus, this finding supports the validity of drug administration by simple immersion for the assessment of BBB and BRB permeability to fluorescent IDs. Using this zebrafish model, we demonstrated that the length of the methylene chain in these fluorescent IDs significantly affected their ability to cross the BBB and BRB via MRPs.

conclusionsWe demonstrated that in vivo assessment of the permeability of the BBB and BRB to fluorescent IDs could be simply and reliably performed using zebrafish. The structure of fluorescent IDs can be flexibly modified and, thus, the permeability of the BBB and BRB to a large number of IDs can be assessed using this zebrafish-based assay. The large amount of data acquired might be useful for in silico analysis to elucidate the precise mechanisms underlying the interactions between chemical structure and the efflux transporters at the BBB and BRB. In turn, understanding these mechanisms may lead to the efficient design of compounds targeting the brain and retina.

Indexed as

Acetic AcidAnimalsBiological TransportBlood-Aqueous BarrierBlood-Retinal BarrierFluorescent DyesIndolesLarvaPermeabilityReproducibility of ResultsZebrafishAcetic AcidFluorescent DyesIndolesindoline

Identifiers

PMID22894547
PMCPMC3807752
OpenAlexW2124769757

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.