Soluble epoxide hydrolase: a novel therapeutic target in stroke.

Soluble epoxide hydrolase: a novel therapeutic target in stroke. Research Abstract Details 

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Soluble epoxide hydrolase: a novel therapeutic target in stroke. Abstract Text:

Wenri Zhang,Ines P Koerner,Ruediger Noppens,Marjorie Grafe,Hsing-Ju Tsai,Christophe Morisseau,Ayala Luria,Bruce D Hammock,John R Falck,Nabil J Alkayed,Wenri Zhang,Ines P Koerner,Ruediger Noppens,Marjorie Grafe,Hsing-Ju Tsai,Christophe Morisseau,Ayala Luria,Bruce D Hammock,John R Falck,Nabil J Alkayed,

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

Soluble epoxide hydrolase: a novel therapeutic target in stroke. Publishing Authors By Initials

W Zhang,IP Koerner,R Noppens,M Grafe,HJ Tsai,C Morisseau,A Luria,BD Hammock,JR Falck,NJ Alkayed,W Zhang,IP Koerner,R Noppens,M Grafe,HJ Tsai,C Morisseau,A Luria,BD Hammock,JR Falck,NJ Alkayed,

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Soluble epoxide hydrolase: a novel therapeutic target in stroke. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cerebral blood flow and metabolism : of

VOLUME: 27

Page Numbers: 1931-40

Journal Abbreviation: J. Cereb. Blood Flow Metab.

ISSN: 0271-678X

DAY: 18

MONTH: 04

YEAR: 2007

Soluble epoxide hydrolase: a novel therapeutic target in stroke. Information

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LANGUAGE: eng

NlmUniqueID: 8112566

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Grant and Affiliation Information for Soluble epoxide hydrolase: a novel therapeutic target in stroke.

AFFILIATION: Department of Anesthesiology & Peri-Operative Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS44313

ACRONYM: NS

MEDLINETA: J Cereb Blood Flow Metab

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