Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia.

Authors: Tu, Ranran; Armstrong, Jillian; Lee, Kin Sing Stephen; Hammock, Bruce D; Sapirstein, Adam; Koehler, Raymond C

Published In Sci Rep, (2018 03 27)

Abstract: Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion. Vehicle or 1 mg/kg TPPU was administered at reperfusion after 90 minutes of focal ischemia and again 24 hours later. Protein expression and activity of sEH increased after reperfusion and activity was decreased by TPPU administration. TPPU decreased infarct volume by 50%, reduced neurologic deficits and improved performance on sensorimotor tasks. Furthermore, TPPU significantly lowered the mRNA expression of interleukin-1beta by 3.5-fold and tumor necrosis factor-alpha by 2.2-fold, increased transforming growth factor-beta mRNA by 1.8-fold, and augmented immunostaining of vascular endothelial growth factor in peri-infarct cortex. Thus, inhibition of sEH at reperfusion significantly reduces infarction and improves sensorimotor function, possibly by suppressing early proinflammatory cytokines and promoting reparative cytokines and growth factors.

PubMed ID: 29588470 Exiting the NIEHS site

MeSH Terms: Animals; Brain Ischemia/complications; Brain Ischemia/drug therapy*; Brain Ischemia/immunology; Brain Ischemia/pathology; Brain/drug effects; Brain/immunology; Brain/pathology; Cerebral Infarction/complications; Cerebral Infarction/drug therapy; Cerebral Infarction/immunology; Cerebral Infarction/pathology; Enzyme Inhibitors/therapeutic use*; Epoxide Hydrolases/antagonists & inhibitors*; Epoxide Hydrolases/immunology; Inflammation/complications; Inflammation/drug therapy*; Inflammation/immunology; Inflammation/pathology; Phenylurea Compounds/therapeutic use*; Piperidines/therapeutic use*; Rats; Rats, Sprague-Dawley; Reperfusion Injury/complications; Reperfusion Injury/drug therapy*; Reperfusion Injury/immunology; Reperfusion Injury/pathology

Back
to Top