Evidence map›Paper›PMID 25904802›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury.

Faith H Brennan, Richard Gordon, Hong W Lao, Patrick J Biggins, Stephen M Taylor, Robin J M Franklin, Trent M Woodruff, Marc J Ruitenberg

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

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% 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

62 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.

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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Faith H BrennanSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
Richard GordonSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
Hong W LaoSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
Patrick J BigginsSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
Stephen M TaylorSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
Robin J M FranklinWellcome Trust-Medical Research Council, Cambridge Stem Cell Institute & Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0AH, United Kingdom.
Trent M WoodruffSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.ORCID http://orcid.org/0000-0003-1382-911X
Marc J RuitenbergSchool of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia, Queensland Brain Institute, University of Queensland, Brisbane, 4072, Australia, and Trauma, Critical Care and Recovery, Brisbane Diamantina Health Partners, Brisbane, 4072, Australia m.ruitenberg@uq.edu.au.
The University of Queensland · AUQueensland Health · AUWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Wellcome Trust 97922
6 · The paper itself

Abstract

This study investigated the role of the complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI). C5ar(-/-) mice, which lack the signaling receptor for C5a, displayed signs of improved locomotor recovery and reduced inflammation during the first week of SCI compared with wild-type mice. Intriguingly, the early signs of improved recovery in C5ar(-/-) mice deteriorated from day 14 onward, with absence of C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, reduced myelin content, and more widespread inflammation at 35 d SCI. Pharmacological blockade of C5aR with a selective antagonist (C5aR-A) during the first 7 d after SCI improved recovery compared with vehicle-treated mice, and this phenotype was sustained up to 35 d after injury. Consistent with observations made in C5ar(-/-) mice, these improvements were, however, lost if C5aR-A administration was continued into the more chronic phase of SCI. Signaling through the C5a-C5aR axis thus appears injurious in the acute period but serves a protective and/or reparative role in the post-acute phase of SCI. Further experiments in bone marrow chimeric mice suggested that the dual and opposing roles of C5aR on SCI outcomes primarily relate to its expression on CNS-resident cells and not infiltrating leukocytes. Additional in vivo and in vitro studies provided direct evidence that C5aR signaling is required during the postacute phase for astrocyte hyperplasia, hypertrophy, and glial scar formation. Collectively, these findings highlight the complexity of the inflammatory response to SCI and emphasize the importance of optimizing the timing of therapeutic interventions.

Indexed as

AnimalsAstrocytesCell ProliferationCells, CulturedComplement ActivationComplement C5aFemaleGliosisInflammationMiceMice, KnockoutMotor ActivityPeptides, CyclicReceptor, Anaphylatoxin C5aRecovery of FunctionSpinal Cord InjuriesComplement C5ahydrocinnamate-(OP(Phe)WR)Peptides, CyclicReceptor, Anaphylatoxin C5aanaphylatoxinCNS traumademyelinating pathologymacrophageoligodendrocyte precursor cellsecondary degeneration

Identifiers

PMID25904802
PMCPMC6605214
OpenAlexW2021561225

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.