ArticleNeuroscience2012
Mechanism of the sex difference in neuronal ischemic cell death.
Article in Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Sex-dependent role of 20-HETE synthesis in outcome from ischemic stroke in rats.Physiological reports · 2026Article
- Protection from oxygen-glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes.In vitro cellular & developmental biology. Animal · 2024Article
- Sex-Specific Response of the Brain Free Oxylipin Profile to Soluble Epoxide Hydrolase Inhibition.Nutrients · 2023Article
- Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Role of Nuclear-Receptor-Related 1 in the Synergistic Neuroprotective Effect of Umbilical Cord Blood and Erythropoietin Combination Therapy in Hypoxic Ischemic Encephalopathy.International journal of molecular sciences · 2022Article
- Human-Induced Pluripotent Stem Cell-Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2022Review
- Article
- Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke.International journal of molecular sciences · 2021Review
- Article
- Toll-Like Receptors Contribute to Sex Differences in Blood Pressure Regulation.Journal of cardiovascular pharmacology · 2020Review
- Pregnancy, postpartum and parity: Resilience and vulnerability in brain health and disease.Frontiers in neuroendocrinology · 2020Review
- Estrogen as a Neuroprotectant in Both Sexes: Stories From the Bird Brain.Frontiers in neurology · 2020Review
- cGMP-dependent protein kinase I in vascular smooth muscle cells improves ischemic stroke outcome in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Necrosis Contributes to the Development of Hypertension in Male, but Not Female, Spontaneously Hypertensive Rats.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Age and Sex Are Critical Factors in Ischemic Stroke Pathology.Endocrinology · 2018Review
- Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.Frontiers in pharmacology · 2018Article
- Cytochrome P450 eicosanoids in cerebrovascular function and disease.Pharmacology & therapeutics · 2017Review
- Effects of erythropoietin and methylprednisolone on AQP4 expression in astrocytes.Molecular medicine reports · 2017Article
- The Biological Function of the Prion Protein: A Cell Surface Scaffold of Signaling Modules.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundStroke risk and outcome are different in men and women. We hypothesized that this is partly due to an inherent difference in susceptibility to ischemia between neurons from male vs. female brains. We tested whether neurons from male rodents are more susceptible to in-vitro ischemia than cells from females, and if this is related to increased expression of soluble epoxide hydrolase (sEH). sEH contributes to neuronal cell death by inactivating neuroprotective epoxyeicosatrienoic acids (EETs).
methodsRodent cortical neurons were cultured, and exposed to oxygen-glucose deprivation (OGD); then cell death was measured. EETs levels were determined by LC-MS/MS. Expression of sEH-encoding ephx2 was determined by qRT-PCR. Western blotting, immunocytochemistry, and hydrolase activity assay assessed protein expression and activity.
resultsCell death after OGD was higher in neurons from males vs. females, which correlated with higher ephx2 mRNA and stronger sEH immunoreactivity. However, EETs levels were similar in both sexes and pharmacological inhibition of the hydrolase domain of sEH did not abolish the sex difference in cell death. Genetic knockout of sEH in mice abolished the sex difference observed in neurons isolated from these mice after OGD.
conclusionsCultured cortical neurons from females are more resistant to ischemia than neurons from males. Neurons from females have less sEH activity compared to neurons from males at baseline, although sEH levels were not measured after OGD. While pharmacological inhibition of the hydrolase domain of sEH does not affect cell death, knockout of the gene encoding sEH eradicates the sex difference seen in wild-type neurons, suggesting a role for further study of the lesser-known phosphatase domain of sEH and its role in sexual dimorphism in neuronal sensitivity to ischemia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.