Evidence map›Paper›PMID 17884256›Full record

ArticleNeurochemistry international2008

TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1.

Jessy J Alexander, Alexander Jacob, Patrick Cunningham, Lauren Hensley, Richard J Quigg

Open access · greenAbstract read
In one paragraph

Article in Neurochemistry international, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

107 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Cerebral perfusion in sepsis-associated delirium.Critical care (London, England) · 2008
    Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Aquaporins in sepsis- an update.Frontiers in immunology · 2024
    Review
  15. Review
  16. Aquaporins: Potential Targets in Inflammatory Diseases.The Eurasian journal of medicine · 2023
    Article
  17. Role of Imaging Modalities andACS chemical neuroscience · 2023
    Article
  18. Review
  19. Article
  20. Review

47 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

5 authors at 1 institution in 1 country.

Jessy J AlexanderDepartment of Medicine, University of Chicago, 5841 South Maryland Avenue, MC5100, Chicago, IL 60637, USA. jalexand@medicine.bsd.uchicago.edu
Alexander Jacob
Patrick Cunningham
Lauren Hensley
Richard J Quigg
University of Chicago · US

Funding

Role of the Complement System in Renal DiseaseR01DK041873 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI QUIGG, RICHARD J. · 1994 to 2011
$3.4M
PATHOGENIC ROLE OF THE COMPLEMENT SYSTEM IN MURINE LUPUSR01DK055357 · NIDDK · UNIVERSITY OF CHICAGO · PI QUIGG, RICHARD J. · 1999 to 2009
$2.5M
INTESTINAL ALLOGRAFT REJECTION--MECHANISMS AND THERAPIESR01AI043579 · NIAID · UNIVERSITY OF CHICAGO · PI NEWELL, KENNETH A · 1998 to 2000
$219k
NIAID NIH HHS R01AI43579NIDDK NIH HHS R01 DK041873NIDDK NIH HHS R01 DK055357NIDDK NIH HHS R01DK41873NIDDK NIH HHS R01DK55357
6 · The paper itself

Abstract

In this study, we demonstrate that mice deficient in TNFR1 (TNFR1(-/-)) were resistant to LPS-induced encephalopathy. Systemic administration of lipopolysaccharide (LPS) induces a widespread inflammatory response similar to that observed in sepsis. Following LPS administration TNFR1(-/-) mice had less caspase-dependent apoptosis in brain cells and fewer neutrophils infiltrating the brain (p<0.039), compared to control C57Bl6 (TNFR1(+/+)) mice. TNFR1-dependent increase in aquaporin (AQP)-4 mRNA and protein expression was observed with a concomitant increase in water content, in brain (18% increase in C57Bl6 mice treated with LPS versus those treated with saline), similar to cerebral edema observed in sepsis. Furthermore, absence of TNFR1 partially but significantly reduced the activation of astrocytes, as shown by immunofluorescence and markedly inhibited iNOS mRNA expression (p<0.01). Septic encephalopathy is a devastating complication of sepsis. Although, considerable work has been done to identify the mechanism causing the pathological alterations in this setting, the culprit still remains an enigma. Our results demonstrate for the first time that endotoxemia leads to inflammation in brain, with alteration in blood-brain barrier, up-regulation of AQP4 and associated edema, neutrophil infiltration, astrocytosis, as well as apoptotic cellular death, all of which appear to be mediated by TNF-alpha signaling through TNFR1.

Indexed as

AnimalsApoptosisAquaporin 4AstrocytesBlood-Brain BarrierBrainBrain Diseases, MetabolicBrain EdemaChemotaxis, LeukocyteEncephalitisGliosisInflammation MediatorsLipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutAqp4 protein, mouseAquaporin 4Inflammation MediatorsLipopolysaccharidesNitric Oxide Synthase Type IIReceptors, Tumor Necrosis Factor, Type IRNA, MessengerTnfrsf1a protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID17884256
PMCPMC3191465
OpenAlexW2029520101

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.