ArticleThe American journal of pathology2009
Soluble epoxide inhibition is protective against cerebral ischemia via vascular and neural protection.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 109 citations in OpenAlex.
- The effects of CYP450 inhibition on cerebrovascular control during rest and mild hypovolemia: An exploratory study in young, healthy adults.Physiological reports · 2025Trial
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.Scientific reports · 2023Article
- Inhibition of soluble epoxide hydrolase reduces paraquat neurotoxicity in rodents.Environmental toxicology and pharmacology · 2023Article
- High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature.International journal of molecular sciences · 2022Article
- Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation.Oxidative medicine and cellular longevity · 2022Article
- Article
- Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice.International journal of molecular sciences · 2021Article
- Soluble epoxide hydrolase inhibition improves cognitive function and parenchymal artery dilation in a hypertensive model of chronic cerebral hypoperfusion.Microcirculation (New York, N.Y. : 1994) · 2021Article
- Multimodal Optical Imaging to Investigate Spatiotemporal Changes in Cerebrovascular Function in AUDA Treatment of Acute Ischemic Stroke.Frontiers in cellular neuroscience · 2021Article
- Article
- Review
- Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.BMC neuroscience · 2020Article
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Cytochrome P450 derived epoxidized fatty acids as a therapeutic tool against neuroinflammatory diseases.Prostaglandins & other lipid mediators · 2020Review
- Protective Effects of the Soluble Epoxide Hydrolase Inhibitor 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea in a Rat Model of Permanent Middle Cerebral Artery Occlusion.Frontiers in pharmacology · 2020Article
- Circadian Variation in Vasoconstriction and Vasodilation Mediators and Baroreflex Sensitivity in Hypertensive Rats.Journal of circadian rhythms · 2019Article
- Soluble epoxide hydrolase modulates immune responses in activated astrocytes involving regulation of STAT3 activity.Journal of neuroinflammation · 2019Article
- Humble beginnings with big goals: Small molecule soluble epoxide hydrolase inhibitors for treating CNS disorders.Progress in neurobiology · 2019Review
- Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of soluble epoxide hydrolase (SEH), the enzyme responsible for degradation of vasoactive epoxides, protects against cerebral ischemia in rats. However, the molecular and biological mechanisms that confer protection in normotension and hypertension remain unclear. Here we show that 6 weeks of SEH inhibition via 2 mg/day of 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) in spontaneously hypertensive stroke-prone (SHRSP) rats protects against cerebral ischemia induced by middle cerebral artery occlusion, reducing percent hemispheric infarct and neurodeficit score without decreasing blood pressure. This level of cerebral protection was similar to that of the angiotensin-converting enzyme inhibitor, enalapril, which significantly lowered blood pressure. SEH inhibition is also protective in normotensive Wistar-Kyoto (WKY) rats, reducing both hemispheric infarct and neurodeficit score. In SHRSP rats, SEH inhibition reduced wall-to-lumen ratio and collagen deposition and increased cerebral microvessel density, although AUDA did not alter middle cerebral artery structure or microvessel density in WKY rats. An apoptosis mRNA expression microarray of brain tissues from AUDA-treated rats revealed that AUDA modulates gene expression of mediators involved in the regulation of apoptosis in neural tissues of both WKY and SHRSP rats. Hence, we conclude that chronic SEH inhibition protects against cerebral ischemia via vascular protection in SHRSP rats and neural protection in both the SHRSP and WKY rats, indicating that SEH inhibition has broad pharmacological potential for treating ischemic stroke.
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