Evidence map›Paper›PMID 18274670›Full record

ArticleThe Journal of clinical investigation2008

A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI.

Constantin von Zur Muhlen, Nicola R Sibson, Karlheinz Peter, Sandra J Campbell, Panop Wilainam, Georges E Grau, Christoph Bode, Robin P Choudhury, Daniel C Anthony

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
10.5field-weighted citation impact, top 2% 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

33 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
  2. Review
  3. Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Review
  10. Article
  11. Article
  12. FeInternational journal of nanomedicine · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Imaging Neuroinflammation - from Bench to Bedside.Journal of clinical & cellular immunology · 2014
    Article
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

9 authors at 1 institution in 1 country.

Constantin von Zur MuhlenDepartment of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom.
Nicola R Sibson
Karlheinz Peter
Sandra J Campbell
Panop Wilainam
Georges E Grau
Christoph Bode
Robin P Choudhury
Daniel C Anthony
University of Oxford · GB

Funding

Medical Research Council G0500853Wellcome Trust
6 · The paper itself

Abstract

Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-alpha, but not IL-1beta or lymphotoxin-alpha (LT-alpha), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-alpha injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies.

Indexed as

Contrast MediaFerric CompoundsPlatelet AdhesivenessAnimalsBinding SitesInterleukin-1betaMagnetic Resonance ImagingMalaria, CerebralMaleMicePlatelet ActivationPlatelet AggregationRatsRats, WistarTumor Necrosis Factor-alphaContrast MediaFerric Compoundsferric oxideInterleukin-1betaTumor Necrosis Factor-alpha

Identifiers

PMID18274670
PMCPMC2242620
OpenAlexW2117621180

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.