Evidence map›Paper›PMID 28057806›Full record

ArticleStroke2017

12/15-Lipoxygenase Inhibition or Knockout Reduces Warfarin-Associated Hemorrhagic Transformation After Experimental Stroke.

Yu Liu, Yi Zheng, Hulya Karatas, Xiaoying Wang, Christian Foerch, Eng H Lo, Klaus van Leyen

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

Article in Stroke, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.9field-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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Ironing out mechanisms of ferroptotic death to tailor new stroke therapies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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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

7 authors at 3 institutions in 2 countries.

Yu LiuFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Yi ZhengFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Hulya KaratasFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Xiaoying WangFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Christian FoerchFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Eng H LoFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.).
Klaus van LeyenFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown (Y.L., Y.Z., H.K., X.W., E.H.L., K.v.L.); Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, China (Y.L.); and Department of Neurology, Goethe University, Frankfurt am Main, Germany (C.F.). klaus_vanleyen@hms.harvard.edu.
Harbin Medical University · CNMassachusetts General Hospital · USSecond Affiliated Hospital of Harbin Medical University · CN

Funding

12-Lipoxygenase and Ischemic Brain Cell DeathR01NS049430 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VAN LEYEN, KLAUS · 2005 to 2015
$3.6M
Effects of Semaphorin 3A on Stroke RecoveryR01NS069939 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VAN LEYEN, KLAUS · 2011 to 2013
$1.0M
NINDS NIH HHS R01 NS049430NINDS NIH HHS R01 NS069939
6 · The paper itself

Abstract

background and purposeFor stroke prevention, patients with atrial fibrillation typically receive oral anticoagulation. The commonly used anticoagulant warfarin increases the risk of hemorrhagic transformation (HT) when a stroke occurs; tissue-type plasminogen activator treatment is therefore restricted in these patients. This study was designed to test the hypothesis that 12/15-lipoxygenase (12/15-LOX) inhibition would reduce HT in warfarin-treated mice subjected to experimental stroke.

methodsWarfarin was dosed orally in drinking water, and international normalized ratio values were determined using a Coaguchek device. C57BL6J mice or 12/15-LOX knockout mice were subjected to transient middle cerebral artery occlusion with 3 hours severe ischemia (model A) or 2 hours ischemia and tissue-type plasminogen activator infusion (model B), with or without the 12/15-LOX inhibitor ML351. Hemoglobin was determined in brain homogenates, and hemorrhage areas on the brain surface and in brain sections were measured. 12/15-LOX expression was detected by immunohistochemistry.

resultsWarfarin treatment resulted in reproducible increased international normalized ratio values and significant HT in both models. 12/15-LOX knockout mice suffered less HT after severe ischemia, and ML351 reduced HT in wild-type mice. When normalized to infarct size, ML351 still independently reduced hemorrhage. HT after tissue-type plasminogen activator was similarly reduced by ML351.

conclusionsIn addition to its benefits in infarct size reduction, 12/15-LOX inhibition also may independently reduce HT in warfarin-treated mice. ML351 should be further evaluated as stroke treatment in anticoagulated patients suffering a stroke, either alone or in conjunction with tissue-type plasminogen activator.

Indexed as

AnimalsAnticoagulantsArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseCerebral HemorrhageEnzyme InhibitorsMaleMiceMice, Inbred C57BLMice, KnockoutStrokeWarfarin12-15-lipoxygenaseAnticoagulantsArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseEnzyme InhibitorsWarfarinatrial fibrillationbrainhemorrhagestrokewarfarin

Identifiers

PMID28057806
PMCPMC5263178
OpenAlexW2571448978

What OpenQuestion holds

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LicenceTDM
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.