Soluble Epoxide Hydrolase: A Novel Therapeutic Target in Stroke

摘要: The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced in brain and perform important biological functions, including protection from ischemic injury. beneficial effect of EETs, however, is limited by their metabolism via soluble epoxide hydrolase (sEH). We tested the hypothesis that sEH inhibition protective against damage vivo a mechanism linked to enhanced cerebral blood flow (CBF). determined expression distribution immunoreactivity (IR) brain, examined inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid butyl ester (AUDA-BE) on CBF infarct size after experimental stroke mice. Mice were administered single intraperitoneal injection AUDA-BE (10 mg/kg) or vehicle at 30 mins before 2-h middle artery occlusion (MCAO) reperfusion, presence absence epoxygenase N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH). Immunoreactivity for was detected vascular non-vascular compartments, with predominant neuronal cell bodies processes. 12-(3-Adamantan-1-ylureido)-dodecanoic plasma up 24 h injection, which associated activity tissue. Finally, significantly reduced MCAO, prevented MS-PPOH. However, regional rates measured iodoantipyrine (IAP) autoradiography end ischemia revealed no differences between AUDA-BE- vehicle-treated findings suggest injury mechanisms, may serve as therapeutic target stroke.