Evidence map›Paper›PMID 19011099›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase.

Michael O Breckwoldt, John W Chen, Lars Stangenberg, Elena Aikawa, Elisenda Rodriguez, Shumei Qiu, Michael A Moskowitz, Ralph Weissleder

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 1 pooled it
10.4field-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

162 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Myeloperoxidase as a therapeutic target for oxidative damage in Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2025
    Review
  6. Review
  7. Review
  8. Article
  9. Quantitative in Vivo Molecular MRI.Advanced materials (Deerfield Beach, Fla.) · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

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 2 institutions in 2 countries.

Michael O BreckwoldtCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, CNY-149, 13th Street, Charlestown, MA 02129, USA.
John W Chen
Lars Stangenberg
Elena Aikawa
Elisenda Rodriguez
Shumei Qiu
Michael A Moskowitz
Ralph Weissleder
Center for Systems Biology · USBrain Physiology Lab · FR

Funding

TRIGEMINOVASCULAR CONTROL OF CEREBRAL BLOOD VESSELSP50NS010828 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MOSKOWITZ, MICHAEL A. · 1985 to 2007
$10.8M
Small Animal Imaging Resource GrantR24CA092782 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, RALPH · 2001 to 2006
$4.2M
MR imaging of myeloperoxidase activityR01HL078641 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, RALPH · 2004 to 2007
$1.5M
Molecular imaging of vascular pathologyK08HL081170 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI CHEN, JOHN W · 2006 to 2010
$666k
NCI NIH HHS R24 CA092782NCI NIH HHS R24-CA92782NHLBI NIH HHS 5K08HL081170NHLBI NIH HHS K08 HL081170NHLBI NIH HHS R01 HL078641NHLBI NIH HHS R01-HL078641NINDS NIH HHS P50 NS010828NINDS NIH HHS P50-NS10828-32
6 · The paper itself

Abstract

Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty in translating animal studies to humans is the lack of a definitive method to confirm and track inflammation in the brain in vivo. Myeloperoxidase (MPO), a key inflammatory enzyme secreted by activated neutrophils and macrophages/microglia, can generate highly reactive oxygen species to cause additional damage in cerebral ischemia. We report here that a functional, enzyme-activatable MRI agent can accurately track the oxidative activity of MPO noninvasively in stroke in living animals. We found that MPO is widely distributed in ischemic tissues, correlates positively with infarct size, and is detected even 3 weeks postinfarction. The peak level of MPO activity, determined by activation of the MPO-sensing agent in vivo and confirmed by MPO activity and quantitative RT-PCR assays, occurred on day 3 after ischemia. Both neutrophils and macrophages/microglia contribute to secrete MPO in the ischemic brain, although neutrophils peak earlier (days 1-3) whereas macrophages/microglia are most abundant later (days 3-7). In contrast to the conventional MRI agent diethylenetriamine-pentatacetate gadolinium, which reports blood-brain barrier disruption, MPO imaging is able to additionally track MPO activity and confirm inflammation on the molecular level in vivo, information that was previously only possible to obtain on ex vivo brain sections and impossible to assess in living human patients. Our findings could allow efficient noninvasive serial screening of therapies targeting inflammation and the use of MPO imaging as an imaging biomarker to risk-stratify patients.

Indexed as

AnimalsDisease Models, AnimalGadolinium DTPAInflammationMagnetic Resonance ImagingMiceMice, Inbred C57BLPeroxidaseStrokeGadolinium DTPAPeroxidase

Identifiers

PMID19011099
PMCPMC2587593
OpenAlexW2164545928

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.