Evidence map›Paper›PMID 27326668›Full record

ArticleNeurobiology of disease2016

Maternal inflammation leads to impaired glutamate homeostasis and up-regulation of glutamate carboxypeptidase II in activated microglia in the fetal/newborn rabbit brain.

Zhi Zhang, Bassam Bassam, Ajit G Thomas, Monica Williams, Jinhuan Liu, Elizabeth Nance, Camilo Rojas, Barbara S Slusher, Sujatha Kannan

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
10.5field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 84 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. The Gut Microbiome and Cardiac Arrhythmias.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. Dynamic Network Connectivity: from monkeys to humans.Frontiers in human neuroscience · 2024
    Review
  14. Targeting glutamate carboxypeptidase II in IBD.Advances in pharmacology (San Diego, Calif.) · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  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

9 authors at 1 institution in 1 country.

Zhi ZhangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Bassam BassamDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Ajit G ThomasJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Monica WilliamsDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Jinhuan LiuDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Elizabeth NanceDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Camilo RojasJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Barbara S SlusherNeurology, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA; Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA.
Sujatha KannanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, 1800 Orleans St, Baltimore, MD 21287, USA. Electronic address: skannan3@jhmi.edu.
Johns Hopkins University · US

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
GCPII Inihibitors for the treatment of chemotherapy-induced neuropathyR01CA161056 · NCI · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH · 2012 to 2016
$1.8M
Mechanisms and novel therapy in intrauterine inflammation induced brain injuryR01HD069562 · NICHD · JOHNS HOPKINS UNIVERSITY · PI KANNAN, SUJATHA · 2012 to 2016
$1.6M
Nanotherapies for the treatment of neurodevelopmental disorders.R01EB018306 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI RANGARAMANUJAM, KANNAN · 2014 to 2017
$1.5M
NCI NIH HHS R01 CA161056NIBIB NIH HHS R01 EB018306NICHD NIH HHS R01 HD069562NIMH NIH HHS P30 MH075673
6 · The paper itself

Abstract

Astrocyte dysfunction and excessive activation of glutamatergic systems have been implicated in a number of neurologic disorders, including periventricular leukomalacia (PVL) and cerebral palsy (CP). However, the role of chorioamnionitis on glutamate homeostasis in the fetal and neonatal brains is not clearly understood. We have previously shown that intrauterine endotoxin administration results in intense microglial 'activation' and increased pro-inflammatory cytokines in the periventricular region (PVR) of the neonatal rabbit brain. In this study, we assessed the effect of maternal inflammation on key components of the glutamate pathway and its relationship to astrocyte and microglial activation in the fetal and neonatal New Zealand white rabbit brain. We found that intrauterine endotoxin exposure at gestational day 28 (G28) induced acute and prolonged glutamate elevation in the PVR of fetal (G29, 1day post-injury) and postnatal day 1 (PND1, 3days post-injury) brains along with prominent morphological changes in the astrocytes (soma hypertrophy and retracted processes) in the white matter tracts. There was a significant increase in glutaminase and N-Methyl-d-Aspartate receptor (NMDAR) NR2 subunit expression along with decreased glial L-glutamate transporter 1 (GLT-1) in the PVR at G29, that would promote acute dysregulation of glutamate homeostasis. This was accompanied with significantly decreased TGF-β1 at PND1 in CP kits indicating ongoing neuroinflammation. We also show for the first time that glutamate carboxypeptidase II (GCPII) was significantly increased in the activated microglia at the periventricular white matter area in both G29 and PND1 CP kits. This was confirmed by in vitro studies demonstrating that LPS activated primary microglia markedly upregulate GCPII enzymatic activity. These results suggest that maternal intrauterine endotoxin exposure results in early onset and long-lasting dysregulation of glutamate homeostasis, which may be mediated by impaired astrocyte function and GCPII upregulation in activated microglia.

Indexed as

AnimalsAnimals, NewbornAstrocytesBrainCytokinesFemaleGlutamate Carboxypeptidase IIHomeostasisInflammationLipopolysaccharidesMicrogliaPregnancyRabbitsReceptors, N-Methyl-D-AspartateUp-RegulationCytokinesGlutamate Carboxypeptidase IILipopolysaccharidesReceptors, N-Methyl-D-AspartateAstrocytesCerebral palsyGlutamateGlutamate carboxypeptidase II (GCPII)MicrogliaPeriventricular leukomalaciaRabbit

Identifiers

PMID27326668
PMCPMC5394739
OpenAlexW2438889909

What OpenQuestion holds

Textmetadata
LicenceTDM
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.