Evidence map›Paper›PMID 30682787›Full record

ArticleJournal of clinical medicine2019

Annexin A1 as Neuroprotective Determinant for Blood-Brain Barrier Integrity in Neonatal Hypoxic-Ischemic Encephalopathy.

Ruth Gussenhoven, Luise Klein, Daan R M G Ophelders, Denise H J Habets, Bernd Giebel, Boris W Kramer, Leon J Schurgers, Chris P M Reutelingsperger, Tim G A M Wolfs

Abstract read
In one paragraph

Article in Journal of clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
–field-weighted citation impact
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

43 citing papers in PubMed.

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  9. Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Loss of Endothelial Annexin A1 Aggravates Inflammation-Induched Vascular Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  15. Review
  16. Article
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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

9 authors.

Ruth GussenhovenDepartment of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. r.gussenhoven@maastrichtuniversity.nl.
Luise KleinDepartment of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. luise.klein@maastrichtuniversity.nl.ORCID 0000-0002-4108-6117
Daan R M G OpheldersDepartment of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. d.ophelders@maastrichtuniversity.nl.ORCID 0000-0001-7410-5102
Denise H J HabetsSchool of Oncology and Developmental Biology (GROW), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl.
Bernd GiebelInstitute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany. bernd.giebel@uk-essen.de.
Boris W KramerDepartment of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. b.kramer@maastrichtuniversity.nl.
Leon J SchurgersDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands. l.schurgers@maastrichtuniversity.nl.ORCID 0000-0001-7867-6957
Chris P M ReutelingspergerDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands. c.reutelingsperger@maastrichtuniversity.nl.
Tim G A M WolfsDepartment of Pediatrics, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands. tim.wolfs@maastrichtuniversity.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Blood-brain barrier (BBB) disruption is associated with hypoxia-ischemia (HI) induced brain injury and life-long neurological pathologies. Treatment options are limited. Recently, we found that mesenchymal stem/stromal cell derived extracellular vesicles (MSC-EVs) protected the brain in ovine fetuses exposed to HI. We hypothesized that Annexin A1 (ANXA1), present in MSC-EVs, contributed to their therapeutic potential by targeting the ANXA1/Formyl peptide receptor (FPR), thereby preventing loss of the BBB integrity. Cerebral ANXA1 expression and leakage of albumin into the fetal ovine brain parenchyma after HI were analyzed by immunohistochemistry. For mechanistic insights, barrier integrity of primary fetal endothelial cells was assessed after oxygen-glucose deprivation (OGD) followed by treatment with MSC-EVs or human recombinant ANXA1 in the presence or absence of FPR inhibitors. Our study revealed that BBB integrity was compromised after HI which was improved by MSC-EVs containing ANXA1. Treatment with these MSC-EVs or ANXA1 improved BBB integrity after OGD, an effect abolished by FPR inhibitors. Furthermore, endogenous ANXA1 was depleted within 24 h after induction of HI in cerebovasculature and ependyma and upregulated 72 h after HI in microglia. Targeting ANXA1/FPR with ANXA1 in the immature brain has great potential in preventing BBB loss and concomitant brain injury following HI.

Indexed as

Annexin A1/Formyl peptide receptor axisblood-brain barriermesenchymal stem cell-derived extracellular vesiclesneonatal hypoxia-ischemiatherapy

Identifiers

PMID30682787
PMCPMC6406389

What OpenQuestion holds

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Registered trials

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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.