Evidence map›Paper›PMID 24413577›Full record

ArticleCritical care medicine2014

A better understanding of why murine models of trauma do not recapitulate the human syndrome.

Lori F Gentile, Dina C Nacionales, M Cecilia Lopez, Erin Vanzant, Angela Cuenca, Alex G Cuenca, Ricardo Ungaro, Tezcan Ozrazgat Baslanti, Bruce A McKinley, Azra Bihorac and 7 more

Abstract readMulticenter Study
In one paragraph

Article in Critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Creating an Extremely Long-lasting Neuroischemic Wound Model.JID innovations : skin science from molecules to population health · 2025
    Article
  2. Review
  3. Review
  4. Transcriptomic responses from improved murine sepsis models can better mimic human surgical sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  5. Article
  6. Article
  7. Modelling physical resilience in ageing mice.Mechanisms of ageing and development · 2019
    Review
  8. Article
  9. Article
  10. Mouse Injury Model of Polytrauma and Shock.Methods in molecular biology (Clifton, N.J.) · 2018
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Impact of haemorrhagic shock intensity on the dynamic of alarmins release in porcine poly-trauma animal model.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2016
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Lori F Gentile1Department of Surgery, University of Florida College of Medicine, Gainesville, FL. 2Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL. 3University of Florida Genetics Institute, University of Florida College of Medicine, Gainesville, FL. 4Department of Anesthesia, University of Florida College of Medicine, Gainesville, FL. 5Department of Surgery, Harborview Medical Center, University of Washington, Seattle, WA. 6Institute on Aging, Division of Biology of Aging, University of Florida College of Medicine, Gainesville, FL.
Dina C Nacionales
M Cecilia Lopez
Erin Vanzant
Angela Cuenca
Alex G Cuenca
Ricardo Ungaro
Tezcan Ozrazgat Baslanti
Bruce A McKinley
Azra Bihorac
Joseph Cuschieri
Ronald V Maier
Frederick A Moore
Christiaan Leeuwenburgh
Henry V Baker
Lyle L Moldawer
Philip A Efron

Funding

Inflammation and the Response to InjuryU54GM062119 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI TOMPKINS, RONALD GARY · 2001 to 2010
$78.6M
University of Florida Older Americans Independence Center (OAIC)P30AG028740 · NIA · UNIVERSITY OF FLORIDA · PI CHRISTIAAN LEEUWENBURGH · 2007 to 2026
$22.8M
Molecular Biology in Burns and TraumaT32GM008721 · NIGMS · UNIVERSITY OF FLORIDA · PI Philip A Efron · 1999 to 2026
$5.0M
REGULATION ON MONOKINE PRODUCTION IN TRAUMA AND SURGERYR01GM040586 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI MOLDAWER, LYLE L · 1988 to 2016
$2.6M
Novel Mechanisms and Approaches to Treat Neonatal SepsisR01GM097531 · NIGMS · UNIVERSITY OF FLORIDA · PI LARSON, SHAWN DAVID, MOLDAWER, LYLE L · 2011 to 2018
$2.3M
Bridging Sustainable Distribution of TRBD Bioinformatics ResourcesR24GM102656 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI XIAO, WENZHONG · 2012 to 2014
$1.6M
PROMISES: Progenitor Endothelial Cells as a Marker of Endothelial Injury and RepaK23GM087709 · NIGMS · UNIVERSITY OF FLORIDA · PI BIHORAC, AZRA · 2010 to 2013
$497k
NIA NIH HHS P30 AG028740NIA NIH HHS P30AG028740NIGMS NIH HHS K23 GM-087709NIGMS NIH HHS K23 GM087709NIGMS NIH HHS R01 GM040586NIGMS NIH HHS R01 GM097531NIGMS NIH HHS R01 GM-40586-24NIGMS NIH HHS R01 GM-80576-06NIGMS NIH HHS T32 GM008721NIGMS NIH HHS T32-GM-008721-13NIGMS NIH HHS U54 GM062119NIGMS NIH HHS U54 GM-062119-10
6 · The paper itself

Abstract

objectiveGenomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared with human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and by examining the response in isolated neutrophil populations.

designPreclinical controlled in vivo laboratory study and retrospective cohort study.

settingLaboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers. SUBJECTS: Six- to 10-week-old and 20- to 24-month-old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (Injury Severity Score > 15) adult (> 18 yr) patients.

interventionsMice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected. MEASUREMENTS AND MAIN

resultsFold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p < 0.001) were compared with human total and enriched blood leukocyte expression analyses of severe trauma patients at 0.5, 1, 4, 7, 14, and 28 days after injury (Glue Grant trauma-related database). We found that increasing the severity of the murine trauma model only modestly improved the correlation in the transcriptomic response with humans, whereas the age of the mice did not. In addition, the genome-wide response to blood neutrophils (rather than total WBC) was also not well correlated between humans and mice. However, the expression of many individual gene families was much more strongly correlated after injury in mice and humans.

conclusionsAlthough overall transcriptomic association remained weak even after adjusting for the severity of injury, age of the animals, timing, and individual leukocyte populations, there were individual signaling pathways and ontogenies that were strongly correlated between mice and humans. These genes are involved in early inflammation and innate/adaptive immunity.

Indexed as

Disease Models, AnimalGene Expression RegulationMiceAdultAgedAged, 80 and overAge FactorsAnalysis of VarianceAnimalsCase-Control StudiesFemaleGene Expression ProfilingGenome-Wide Association StudyHumansInjury Severity ScoreLeukocytes

Identifiers

PMID24413577
PMCPMC4283139

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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.