Evidence map›Paper›PMID 27838820›Full record

ArticleTranslational stroke research2017

Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia.

Kazim Yigitkanli, Yi Zheng, Anton Pekcec, Eng H Lo, Klaus van Leyen

Open access · greenAbstract read
In one paragraph

Article in Translational stroke research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 63 citations in OpenAlex.

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  15. Role of Ferroptosis in Stroke.Cellular and molecular neurobiology · 2023
    Review
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  17. Article
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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 3 institutions in 2 countries.

Kazim YigitkanliNeuroprotection Research Laboratory, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA, 02129, USA.
Yi ZhengNeuroprotection Research Laboratory, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA, 02129, USA.
Anton PekcecNeuroprotection Research Laboratory, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA, 02129, USA.
Eng H LoNeuroprotection Research Laboratory, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA, 02129, USA.
Klaus van LeyenNeuroprotection Research Laboratory, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA, 02129, USA. klaus_vanleyen@hms.harvard.edu.
Massachusetts General Hospital · USBoehringer Ingelheim (Germany) · DEHarvard University · US

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
Novel 12/15 lipoxygenase inhibitors for the treatment of strokeR21NS087165 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VAN LEYEN, KLAUS · 2014 to 2015
$576k
NINDS NIH HHS R01 NS049430NINDS NIH HHS R01 NS069939NINDS NIH HHS R21 NS087165
6 · The paper itself

Abstract

Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus. Furthermore, 12/15-LOX co-localized with apoptosis-inducing factor (AIF), a mediator of non-caspase-related apoptosis in the cortex. In contrast, caspase-3 activation was more prevalent in the hippocampus. 12/15-lipoxygenase knockout mice were protected against global cerebral ischemia compared to wild-type mice, accompanied by reduced neurologic impairment. The lipoxygenase inhibitor LOXBlock-1 similarly reduced neuronal cell death both when pre-administered and when given at a therapeutically relevant time point 1 h after onset of ischemia. These findings suggest a pivotal role for 12/15-LOX in both caspase-dependent and caspase-independent apoptotic pathways following global cerebral ischemia and suggest a novel therapeutic approach to reduce brain injury following cardiac arrest.

Indexed as

AnimalsApoptosisApoptosis Inducing FactorArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseBrainBrain InjuriesBrain IschemiaCerebral CortexCorpus StriatumHippocampusMaleMiceMice, Inbred C57BLMice, KnockoutNeuronsAlox15 protein, mouseApoptosis Inducing FactorArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseApoptosisCardiac arrestCortexGlobal cerebral ischemiaHippocampusLipoxygenase

Identifiers

PMID27838820
PMCPMC5350054
OpenAlexW2552098855

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.