Evidence map›Paper›PMID 24681156›Full record

ArticleExperimental neurology2014

Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits.

Chelsea E Corser-Jensen, Dayton J Goodell, Ronald K Freund, Predrag Serbedzija, Robert C Murphy, Santiago E Farias, Mark L Dell'Acqua, Lauren C Frey, Natalie Serkova, Kim A Heidenreich

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

Article in Experimental neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  4. Editorial Board Members' Collection Series: "Neuroinflammation".International journal of molecular sciences · 2025
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  16. Montelukast reduces seizures in pentylenetetrazol-kindled mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2016
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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

10 authors at 1 institution in 1 country.

Chelsea E Corser-JensenNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Dayton J GoodellNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Ronald K FreundDepartment of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Predrag SerbedzijaDepartment of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Robert C MurphyNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Santiago E FariasNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Mark L Dell'AcquaNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Lauren C FreyDepartment of Neurology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Natalie SerkovaDepartment of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Kim A HeidenreichNeuroscience Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: kim.heidenreich@ucdenver.edu.
University of Colorado Anschutz Medical Campus · US

Funding

STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
NEUROSCIENCE TRAINING GRANTT32HD041697 · NICHD · UNIVERSITY OF COLORADO DENVER · PI RESTREPO, DIEGO · 2001 to 2015
$2.4M
Preclinical Investigation of 5-lipoxygenase activating protein inhibitors for TBIR21NS079435 · NINDS · UNIVERSITY OF COLORADO DENVER · PI HEIDENREICH, KIM A · 2013 to 2014
$423k
NICHD NIH HHS 5T32HD041697NICHD NIH HHS T32 HD041697NIGMS NIH HHS GM069338NIGMS NIH HHS U54 GM069338NINDS NIH HHS R01NS040710NINDS NIH HHS R21 NS079435NINDS NIH HHS R21NS079435
6 · The paper itself

Abstract

Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in the brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arm water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits.

Indexed as

AnimalsBrainBrain InjuriesChlorobenzenesCognition DisordersHippocampusIndolesLeukotrienesLipoxygenase InhibitorsLong-Term PotentiationMaleMaze LearningRatsRats, Sprague-DawleyTandem Mass SpectrometryChlorobenzenesIndolesLeukotrienesLipoxygenase InhibitorsMK-886Blood–brain barrierEdemaFLAP inhibitorHippocampusLeukotrienesLong-term potentiationMemory and learningNeuroinflammationTraumatic brain injury

Identifiers

PMID24681156
PMCPMC4731038
OpenAlexW2079233663

What OpenQuestion holds

Textmetadata
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.