Evidence map›Paper›PMID 31369614›Full record

ArticlePloS one2019

Toll-like receptor 4 deficiency or inhibition does not modulate survival and neurofunctional outcome in a murine model of cardiac arrest and resuscitation.

Stefan Bergt, Andrea Grub, Melanie Mueller, Rika Bajorat, Ivan Barilar, Brigitte Vollmar, Jan Patrick Roesner, Nana-Maria Wagner

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Stefan BergtClinic for Anesthesiology and Critical Care Medicine, Rostock University Medical Center, Rostock, Germany.
Andrea GrubClinic for Anesthesiology and Critical Care Medicine, Rostock University Medical Center, Rostock, Germany.
Melanie MuellerClinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.
Rika BajoratClinic for Anesthesiology and Critical Care Medicine, Rostock University Medical Center, Rostock, Germany.
Ivan BarilarMolecular and Experimental Mycobacteriology, Priority Area Infections, Research Center Borstel, Borstel, Germany.
Brigitte VollmarInstitute for Experimental Surgery, Rostock University Medical Center, Rostock, Germany.
Jan Patrick RoesnerClinic for Anesthesiology and Critical Care Medicine, Rostock University Medical Center, Rostock, Germany.
Nana-Maria WagnerClinic for Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Muenster, Muenster, Germany.ORCID 0000-0002-4610-6666
University of Rostock · DEUniversity Hospital Münster · DEResearch Center Borstel - Leibniz Lung Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients experiencing cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) often die or suffer from severe neurological impairment. Post resuscitation syndrome is characterized by a systemic inflammatory response. Toll-like receptor 4 (TLR4) is a major mediator of inflammation and TLR4 has been implicated in the pathogenesis of post-resuscitation encephalopathy. The aim of this study was to evaluate whether TLR4 deficiency or inhibition can modulate survival and neurofunctional outcome after CA/CPR.

methodsFollowing intubation and central venous cannulation, CA was induced in wild type (C57Bl/6J, n = 38), TLR4 deficient (TLR4-/-, n = 37) and TLR4 antibody treated mice (5mg/kg MTS510, n = 15) by high potassium. After 10min, CPR was performed using a modified sewing machine until return of spontaneous circulation (ROSC). Cytokines and cerebral TNFalpha levels were measured 8h after CA/CPR. Survival, early neurological recovery, locomotion, spatial learning and memory were assessed over a period of 28 days.

resultsFollowing CA/CPR, all mice exhibited ROSC and 31.5% of wild type mice survived until day 28. Compared to wild type mice, neither TLR4-/- nor MTS510 treated wild type mice had statistically significant altered survival following CA/CPR (51.3 and 26.7%, P = 0.104 and P = 0.423 vs. WT, respectively). Antibody-treated but not TLR4-/- mice had higher IL-1β and IL-6 levels and TLR4-/- mice had higher IL-10 and cerebral TNFalpha levels. No differences existed between mice of all groups in early neurological recovery, locomotion, spatial learning ability or remembrance.

conclusionTherapeutic strategies targeting TLR4 may not be suitable for the reduction of mortality or neurofunctional impairment after CA/CPR.

Indexed as

Cardiopulmonary ResuscitationAnimalsBrain DiseasesCytokinesDisease Models, AnimalFemaleHeart ArrestHemodynamicsMiceMice, Inbred C57BLMice, KnockoutSystemic Inflammatory Response SyndromeToll-Like Receptor 4Tumor Necrosis Factor-alphaCytokinesTlr4 protein, mouseToll-Like Receptor 4Tumor Necrosis Factor-alpha

Identifiers

PMID31369614
PMCPMC6675321
OpenAlexW2966154222

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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.