Evidence map›Paper›PMID 23277546›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications.

Enrico Cristante, Simon McArthur, Claudio Mauro, Elisa Maggioli, Ignacio A Romero, Marzena Wylezinska-Arridge, Pierre O Couraud, Jordi Lopez-Tremoleda, Helen C Christian, Babette B Weksler and 2 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed
5.4field-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

120 citing papers in PubMed, 194 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Role of neutrophils in regulating vascular permeability in inflammatory and autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Annexin A1: The dawn of ischemic stroke (Review).Molecular medicine reports · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. The role of annexins in central nervous system development and disease.Journal of molecular medicine (Berlin, Germany) · 2024
    Review
  15. Review
  16. Annexin A1 in the nervous and ocular systems.Neural regeneration research · 2024
    Review
  17. Review
  18. Article
  19. Article
  20. Article

60 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

12 authors at 7 institutions in 3 countries.

Enrico CristanteWilliam Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Simon McArthur
Claudio Mauro
Elisa Maggioli
Ignacio A Romero
Marzena Wylezinska-Arridge
Pierre O Couraud
Jordi Lopez-Tremoleda
Helen C Christian
Babette B Weksler
Andrea Malaspina
Egle Solito
Queen Mary University of London · GBWilliam Harvey Research Institute · GBImperial College London · GBCornell University · USInserm · FRThe Open University · GBUniversity of Oxford · GB

Funding

British Heart Foundation FS/12/38/29640Wellcome TrustWellcome Trust 085123Wellcome Trust 085983
6 · The paper itself

Abstract

The blood-brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is expressed in brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1(-/-) mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions, essentially related to changes in the actin cytoskeleton, which stabilizes tight and adherens junctions. This situation is reminiscent of early MS pathology, a relationship confirmed by our detection of a selective loss of ANXA1 in the plasma and cerebrovascular endothelium of patients with MS. Importantly, this loss is swiftly restored by i.v. administration of human recombinant ANXA1. Analysis in vitro confirms that treatment of cerebrovascular endothelial cells with recombinant ANXA1 restores cell polarity, cytoskeleton integrity, and paracellular permeability through inhibition of the small G protein RhoA. We thus propose ANXA1 as a critical physiological regulator of BBB integrity and suggest it may have utility in the treatment of MS, correcting BBB function and hence ameliorating disease.

Indexed as

Actin CytoskeletonAdherens JunctionsAdultAgedAnimalsAnnexin A1Blood-Brain BarrierCapillary PermeabilityCell LineEndothelial CellsFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutAnnexin A1annexin A1, mouseRecombinant ProteinsrhoA GTP-Binding ProteinRHOA protein, humanTight Junction Proteins

Identifiers

PMID23277546
PMCPMC3549094
OpenAlexW2052740190

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.