Soluble epoxide hydrolase inhibition: Targeting multiple mechanisms of ischemic brain injury with a single agent

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Abstract

Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids termed epoxyeicosatrienoic acids (EETs). Genetic variations in the sEH gene, designated EPHX2, are associated with ischemic stroke risk. In experimental studies, sEH inhibition and gene deletion reduce infarct size after focal cerebral ischemia in mice. Although the precise mechanism of protection afforded by sEH inhibition remains under investigation, EETs exhibit a wide array of potentially beneficial actions in stroke, including vasodilation, neuroprotection, promotion of angiogenesis and suppression of platelet aggregation, oxidative stress and postischemic inflammation. Herein, we argue that by capitalizing on this broad protective profile, sEH inhibition represents a prototype 'combination therapy' targeting multiple mechanisms of stroke injury with a single agent.

Original languageEnglish (US)
Pages (from-to)179-199
Number of pages21
JournalFuture Neurology
Volume4
Issue number2
DOIs
StatePublished - Jun 19 2009

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Keywords

  • Cerebral blood flow
  • Cerebral ischemia
  • Combination therapy
  • Epoxyelcosatrienoic acids
  • Soluble epoxide hyrdolase
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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