Evidence map›Paper›PMID 26842664›Full record

ArticleJournal of neuroinflammation2016

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

Daan R M G Ophelders, Ruth Gussenhoven, Martin Lammens, Benno Küsters, Matthew W Kemp, John P Newnham, Matthew S Payne, Suhas G Kallapur, Allan H Jobe, Luc J Zimmermann and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Treatment ofAJOG global reports · 2026
    Article
  3. Article
  4. The neural and cardiovascular effects of exposure of gram-positive bacterial inflammation in preterm fetal sheep.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  5. Review
  6. CouldJournal of clinical medicine · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. The diagnostic performance of the beta-glucan assay in the detection of intra-amniotic infection with Candida species.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2019
    Article
  11. Review
  12. Infectious diseases in obstetrics and gynecology · 2017
    Review
  13. Article
  14. 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

12 authors at 5 institutions in 4 countries.

Daan R M G OpheldersDepartment of Pediatrics, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. d.ophelders@maastrichtuniversity.nl.
Ruth GussenhovenDepartment of Pediatrics, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. r.gussenhoven@maastrichtuniversity.nl.
Martin LammensDepartment of Pathology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. martin.lammens@uza.be.
Benno KüstersDepartment of Pathology, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. b.kuesters@radboudumc.nl.
Matthew W KempSchool of Women's and Infants' Health, The University of Western Australia (M550), 35 Stirling Highway, Crawley, WA, 6009, Australia. matthew.kemp@uwa.edu.au.
John P NewnhamSchool of Women's and Infants' Health, The University of Western Australia (M550), 35 Stirling Highway, Crawley, WA, 6009, Australia. john.newnham@uwa.edu.au.
Matthew S PayneSchool of Women's and Infants' Health, The University of Western Australia (M550), 35 Stirling Highway, Crawley, WA, 6009, Australia. matthew.payne@uwa.edu.au.
Suhas G KallapurDivision of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45208, USA. suhas.Kallapur@cchmc.org.
Allan H JobeDivision of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45208, USA. alan.jobe@cchmc.org.
Luc J ZimmermannDepartment of Pediatrics, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. luc.zimmermann@mumc.nl.
Boris W KramerDepartment of Pediatrics, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. b.kramer@maastrichtuniversity.nl.
Tim G A M WolfsDepartment of Pediatrics, Maastricht University Medical Center, PO box 5800, Maastricht, 6202 AZ, The Netherlands. tim.wolfs@maastrichtuniversity.nl.
Maastricht University · NLUniversity of Western Australia · AUCincinnati Children's Hospital Medical Center · USAntwerp University Hospital · BEUniversity Medical Center · US

Funding

Mechanisms of Fetal Inflammatory Response Syndrome Induced by ChorioamnionitisR01HD057869 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI KALLAPUR, SUHAS · 2009 to 2013
$1.6M
NICHD NIH HHS HD 57869NICHD NIH HHS R01 HD057869
6 · The paper itself

Abstract

backgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.

methodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.

resultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.

conclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury.

Indexed as

AnimalsBrain InjuriesCalcium-Binding ProteinsCandida albicansCandidiasisCaspase 3Disease Models, AnimalDNA-Binding ProteinsEncephalitisEnzyme-Linked Immunosorbent AssayFemaleFluoresceinsGranulocyte Colony-Stimulating FactorInterleukin-3Interleukin-6Ki-67 AntigenAIF1 protein, humanCalcium-Binding ProteinsCaspase 3DNA-Binding ProteinsFluoresceinsfluoro-jade CGranulocyte Colony-Stimulating FactorInterleukin-3Interleukin-6Ki-67 AntigenMicrofilament ProteinsMyelin Basic ProteinmyelopoietinNerve Tissue ProteinsRecombinant Fusion Proteins

Identifiers

PMID26842664
PMCPMC4739103
OpenAlexW2253473696

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.