Evidence map›Paper›PMID 11896164›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002

Microglial activation and beta -amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice.

Paul T Jantzen, Karen E Connor, Giovanni DiCarlo, Gary L Wenk, John L Wallace, Amyn M Rojiani, Domenico Coppola, Dave Morgan, Marcia N Gordon

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
26.9field-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

118 citing papers in PubMed, 343 citations in OpenAlex.

  1. Trial
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  7. Review
  8. Microglia in Alzheimer's Disease: a Key Player in the Transition Between Homeostasis and Pathogenesis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  9. Article
  10. Review
  11. Review
  12. Cyclooxygenase-2 Induced the β-Amyloid Protein Deposition and Neuronal Apoptosis Via Upregulating the Synthesis of Prostaglandin ENeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Inflammasomes as therapeutic targets for Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2017
    Review
  20. Article

58 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

9 authors at 3 institutions in 2 countries.

Paul T JantzenDepartment of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, Florida 33612, USA.
Karen E Connor
Giovanni DiCarlo
Gary L Wenk
John L Wallace
Amyn M Rojiani
Domenico Coppola
Dave Morgan
Marcia N Gordon
University of South Florida · USUniversity of Arizona · USUniversity of Calgary · CA

Funding

TRANSGENIC MICE, INFLAMMATION &THE ALZHEIMER PHENOTYPER01AG015490 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI GORDON, MARCIA N · 1999 to 2012
$3.3M
NIA NIH HHS AG 15490NIA NIH HHS R01 AG015490
6 · The paper itself

Abstract

3-4-(2-Fluoro-alpha-methyl-[1,1'-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester (NCX-2216), a nitric oxide (NO)-releasing derivative of the cyclooxygenase-1-preferring nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen, dramatically reduced both beta-amyloid (Abeta) loads and Congo red staining in doubly transgenic (Tg) amyloid precursor protein plus presenilin-1 mice when administered at 375 ppm in diet between 7 and 12 months of age. This reduction was associated with a dramatic increase in the number of microglia expressing major histocompatibility complex-II antigen, a marker for microglial activation. In contrast, ibuprofen at 375 ppm in diet caused modest reductions in Abeta load but not Congo red staining, suggesting that the effects of this nonselective NSAID were restricted primarily to nonfibrillar deposits. We detected no effects of the cyclooxygenase-2-selective NSAID celecoxib at 175 ppm on amyloid deposition. In short-term studies of 12-month-old Tg mice, we found that the microglia-activating properties of NCX-2216 (7.5 mg small middle dot kg(-1) small middle dot d(-1), s.c.) were present after 2 weeks of treatment. Microglia were not activated by NCX-2216 in non-Tg mice lacking Abeta deposits, nor were microglia activated in Tg animals by flurbiprofen (5 mg small middle dot kg(-1) small middle dot d(-1)) alone. These data are consistent with the argument that activated microglia can clear Abeta deposits. We conclude that the NO-generating component of NCX-2216 confers biological actions that go beyond those of typical NSAIDs. In conclusion, NCX-2216 is more efficacious than ibuprofen or celecoxib in clearing Abeta deposits from the brains of Tg mice, implying potential benefit in the treatment of Alzheimer's dementia.

Indexed as

Administration, OralAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAntigens, DifferentiationAnti-Inflammatory Agents, Non-SteroidalCelecoxibCell CountDisease Models, AnimalDose-Response Relationship, DrugDrug Administration ScheduleDrug Evaluation, PreclinicalFlurbiprofenFrontal LobeHippocampus(3-4-(2-fluoromethyl-(1,1'-biphenyl)-4-acetyloxy)-3-methoxyphenyl)-2-propenoic acid 4-nitrooxy butyl esterAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAntigens, DifferentiationAnti-Inflammatory Agents, Non-SteroidalCelecoxibFlurbiprofenHistocompatibility Antigens Class IIIbuprofenMembrane ProteinsNitric OxidePresenilin-1PyrazolesSulfonamides

Identifiers

PMID11896164
PMCPMC6758281
OpenAlexW2137497029

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.