Evidence map›Paper›PMID 25881123›Full record

ArticleJournal of neuroinflammation2015

Treatment with AMD3100 attenuates the microglial response and improves outcome after experimental stroke.

Helene L Walter, Gerlinde van der Maten, Ana Rita Antunes, Tadeusz Wieloch, Karsten Ruscher

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2015. 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
3.2field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 44 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

5 authors at 1 institution in 1 country.

Helene L WalterLaboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden. helene.walter@uk-koeln.de.
Gerlinde van der MatenLaboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden. g.h.van.der.maten@student.rug.nl.
Ana Rita AntunesLaboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden. ana.antunes@med.lu.se.
Tadeusz WielochLaboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden. tadeusz.wieloch@med.lu.se.
Karsten RuscherLaboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden. karsten.ruscher@med.lu.se.
Lund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecovery of lost neurological function after stroke is limited and dependent on multiple mechanisms including inflammatory processes. Selective pharmacological modulation of inflammation might be a promising approach to improve stroke outcome.

methodsWe used 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and potential allosteric agonist to CXCR7, administered to mice twice daily from day 2 after induction of photothrombosis (PT). In addition to functional outcome, the dynamics of post-stroke microglia response were monitored in vivo by 2-photon-laser-microscopy in heterozygous transgenic CX3CR1-green fluorescent protein (GFP) mice (CX3CR1(GFP/+)) and complemented with analyses for fractalkine (FKN) and pro-inflammatory cytokines.

resultsWe found a significantly enhanced recovery and modified microglia activation without affecting infarct size in mice treated with AMD3100 after PT. AMD3100 treatment significantly reduced the number of microglia in the peri-infarct area accompanied by stabilization of soma size and ramified cell morphology. Within the ischemic infarct core of AMD3100 treated wild-type mice we obtained significantly reduced levels of the endogenous CX3CR1 ligand FKN and the pro-inflammatory cytokines interleukin (IL)-1β and IL-6. Interestingly, in CX3CR1-deficient mice (homozygous transgenic CX3CR1-GFP mice) subjected to PT, the levels of FKN were significantly lower compared to their wild-type littermates. Moreover, AMD3100 treatment did not induce any relevant changes of cytokine levels in CX3CR1 deficient mice.

conclusionAfter AMD3100 treatment, attenuation of microglia activation contributes to enhanced recovery of lost neurological function in experimental stroke possibly due to a depression of FKN levels in the brain. We further hypothesize that this mechanism is dependent on a functional receptor CX3CR1.

Indexed as

AnimalsBenzylaminesBrain InfarctionCalcium-Binding ProteinsCyclamsCytokinesDisease Models, AnimalGene Expression RegulationGreen Fluorescent ProteinsHeterocyclic CompoundsMaleMiceMice, Inbred C57BLMice, TransgenicMicrofilament ProteinsMicrogliaAif1 protein, mouseBenzylaminesCalcium-Binding ProteinsCyclamsCytokinesGreen Fluorescent ProteinsHeterocyclic CompoundsMicrofilament ProteinsNeuroprotective AgentsplerixaforReceptors, Interleukin-8A

Identifiers

PMID25881123
PMCPMC4329193
OpenAlexW2122921041

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.