Journal
FUTURE NEUROLOGY
Volume 4, Issue 2, Pages 179-199Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/14796708.4.2.179
Keywords
cerebral blood flow; cerebral ischemia; combination therapy; epoxyeicosatrienoic acids; soluble epoxide hydrolase; stroke
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Funding
- NINDS NIH HHS [R01 NS044313, P30 NS061800, R01 NS044313-06] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P30NS061800, R01NS044313] Funding Source: NIH RePORTER
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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.
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