ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2013
Role of soluble epoxide hydrolase in exacerbation of stroke by streptozotocin-induced type 1 diabetes mellitus.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Endothelial expression of human soluble epoxide hydrolase worsens acute microvascular and tissue injury after stroke in female mice with early-stage diabetes mellitus.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Melatonin at repeated doses alleviates hyperglycemia-exacerbated cerebral ischemia-reperfusion injury at 72 h via anti-inflammation and anti-apoptosis.IBRO neuroscience reports · 2024Article
- Differential lipid signaling from CD4Frontiers in immunology · 2024Article
- Melatonin mitigates type 1 diabetes-aggravated cerebral ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic effects.Brain and behavior · 2023Article
- Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Article
- Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice.International journal of molecular sciences · 2021Article
- The Impact of the CaBiomolecules · 2021Review
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and ActsFrontiers in pharmacology · 2021Article
- Macrophage polarization is linked to CaJournal of lipid research · 2020Article
- Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke.Neuropsychiatric disease and treatment · 2019Article
- Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics.Pharmacology & therapeutics · 2018Review
- Review
- Cytochrome P450 eicosanoids in cerebrovascular function and disease.Pharmacology & therapeutics · 2017Review
- The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases.Advances in nutrition (Bethesda, Md.) · 2016Review
- The protection conferred against ischemia-reperfusion injury in the diabetic brain by N-acetylcysteine is associated with decreased dicarbonyl stress.Free radical biology & medicine · 2016Article
- The Natural Flavonoid Pinocembrin: Molecular Targets and Potential Therapeutic Applications.Molecular neurobiology · 2016Review
- Cyclooxygenase- and cytochrome P450-derived eicosanoids in stroke.Prostaglandins & other lipid mediators · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hyperglycemia worsens stroke, yet rigorous glycemic control does not improve neurologic outcome. An alternative is to target downstream molecular mediator(s) triggered by hyperglycemia but independent of prevailing glycemia. Soluble epoxide hydrolase (sEH) is a potential mediator of injury via its metabolism of neuroprotective epoxyeicosatrienoic acids (EETs). We tested whether hyperglycemia exacerbates cerebral injury by upregulating sEH and decreasing brain EET levels. Type 1 diabetes mellitus was modeled by streptozotocin (STZ; 50 mg/kg per day intraperitoneally, 5 days) in male mice. At 4 weeks, STZ-treated and control mice underwent 45-minute middle cerebral artery occlusion (MCAO) with or without sEH blockade by trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB; 1 mg/kg intraperitoneally daily for 6 days before MCAO). The STZ-treated mice had increased sEH mRNA expression in cerebral vessels and decreased EET concentrations in brain. There was no difference in cortical perfusion between groups. The STZ-treated mice sustained larger brain infarct than controls. Pretreatment with t-AUCB eliminated the difference in infarct size and EETs concentration between STZ-treated mice and controls, without altering glycemia. We conclude that type 1 diabetes mellitus upregulates sEH mRNA and decreases concentrations of neuroprotective EETs within the brain, leading to worse stroke outcome. The data indicate that sEH antagonism may be beneficial in the setting of hyperglycemic stroke.
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