Evidence map›Paper›PMID 41634982›Full record

ArticlePhysiological reports2026

Sex-dependent role of 20-HETE synthesis in outcome from ischemic stroke in rats.

Rongrong Zhang, Yanrong Shi, Suyi Cao, Raymond C Koehler, Zeng-Jin Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Physiological reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. 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

5 authors.

Rongrong ZhangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Yanrong ShiDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Suyi CaoDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Raymond C KoehlerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-5890-9992
Zeng-Jin YangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The lipid mediator 20-HETE is produced by ω-hydroxylation of arachidonic acid mediated by cytochrome P450 (CYP) enzymes including CYP4A, which has four distinct isoforms in rodents. Several laboratories demonstrated that 20-HETE synthesis inhibition reduces infarct volume following middle cerebral artery occlusion (MCAO) in male animals. Here, we investigated whether neuroprotection with the 20-HETE synthesis inhibitor HET0016 administered after transient MCAO in rats differs by sex and whether ischemia differentially induces Cyp4a genes in a sex-dependent manner. HET0016 significantly improved sensorimotor performance and reduced infarct volume compared to vehicle treatment in males. However, these improvements were less consistent in females. Cyp4a2 and Cyp4a3 genes were detected at similar levels in brain tissue from male and female rats undergoing sham surgery or MCAO/reperfusion. Interestingly, the Cyp4a8 gene was detectable in intact and castrated males and increased 3-4-fold after MCAO. In contrast, Cyp4a8 was undetectable in brains of intact or ovariectomized female rats. Oxygen-glucose deprivation in cultured murine neurons revealed male-selective induction of the homolog gene Cyp4a12a, the knockdown of which blocked the increase in 20-HETE. These results indicate that innate male-selective Cyp4a gene induction and 20-HETE signaling are significant factors that can contribute to sex differences in the outcomes from ischemic stroke.

Indexed as

Hydroxyeicosatetraenoic AcidsInfarction, Middle Cerebral ArteryIschemic StrokeAmidinesAnimalsCytochrome P-450 CYP4AFemaleMaleNeuroprotective AgentsRatsRats, Sprague-DawleySex Factors20-hydroxy-5,8,11,14-eicosatetraenoic acidAmidinesCytochrome P-450 CYP4AHET0016Hydroxyeicosatetraenoic AcidsNeuroprotective Agentscastrationcytochrome P450 4Amiddle cerebral artery occlusionovariectomyoxygen–glucose deprivationω‐hydroxylase

Identifiers

PMID41634982
PMCPMC12868388

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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.