Evidence map›Paper›PMID 30602353›Full record

ArticleStroke2019

Impact of 12/15-Lipoxygenase on Brain Injury After Subarachnoid Hemorrhage.

Thomas Gaberel, Clément Gakuba, Yi Zheng, Matthieu Lépine, Eng H Lo, Klaus van Leyen

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

Article in Stroke, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Key Phytochemicals and Biological Functions ofFrontiers in pharmacology · 2021
    Article
  14. Ferroptosis and Its Multifaceted Roles in Cerebral Stroke.Frontiers in cellular neuroscience · 2021
    Review
  15. Article
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

6 authors at 3 institutions in 2 countries.

Thomas GaberelFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (T.G., C.G., Y.Z., E.H.L., K.v.L.).
Clément GakubaFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (T.G., C.G., Y.Z., E.H.L., K.v.L.).
Yi ZhengFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (T.G., C.G., Y.Z., E.H.L., K.v.L.).
Matthieu LépineNormandie Université, UNICAEN, INSERM, UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Caen, France (M.L.).
Eng H LoFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (T.G., C.G., Y.Z., E.H.L., K.v.L.).
Klaus van LeyenFrom the Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA (T.G., C.G., Y.Z., E.H.L., K.v.L.).
Harvard University · USMassachusetts General Hospital · USCyceron · FR

Funding

12-Lipoxygenase and Ischemic Brain Cell DeathR01NS049430 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI VAN LEYEN, KLAUS · 2005 to 2015
$3.6M
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 R21 NS087165
6 · The paper itself

Abstract

Background and Purpose- Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Oxidative stress contributes to brain injury, but the mechanisms have been poorly studied. Here, we evaluated the role of 12/15-lipoxygenase (12/15-LOX), an enzyme known to cause cell death in ischemic stroke, on brain injury in a mouse model of SAH. Methods- C57Bl6 wild-type mice and Alox15 knockout mice were subjected to SAH using a direct blood injection technique. In SAH wild-type mice, half received the 12/15-LOX inhibitor ML351 and half received vehicle. Immunohistochemistry, brain edema, blood-brain barrier leakage and functional outcomes were assessed 1 and 3 days after SAH induction. Results- SAH led to increased 12/15-LOX in macrophages of the brain parenchyma, adjacent to the subarachnoid blood. Neuronal cell death after SAH was reduced by ML351 and in Alox15 knockout mice. Similarly, SAH induced brain edema, which was 12/15-LOX dependent. Finally, Alox15 gene knockout and inhibitor treatment in wild-type mice with SAH led to an improved behavioral outcome. Conclusions- 12/15-LOX is overexpressed in macrophages after SAH in mice, and inhibition of the 12/15-LOX pathway decreases brain injury and improves neurological outcome. This study suggests 12/15-LOX as a novel therapeutic target to limit brain injury after SAH.

Indexed as

Arachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseBrain InjuriesMacrophagesOxidative StressSubarachnoid HemorrhageAnimalsDisease Models, AnimalIsoxazolesLipoxygenase InhibitorsMiceMice, KnockoutNaphthalenesAlox15 protein, mouseArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseIsoxazolesLipoxygenase InhibitorsML351 compoundNaphthalenesblood-brain barrierbrain injurylipoxygenaseoxidative stresssubarachnoid hemorrhage

Identifiers

PMID30602353
PMCPMC6349484
OpenAlexW2908108843

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.