New Therapeutic Target for Stroke

Bruce D. Hammock, Ph.D.
University of California Davis
NIEHS Grants R01ES002710 and P42ES004699

New research by NIEHS-funded investigator Bruce Hammock at the University of California Davis has identified the enzyme soluble epoxide hydrolase (sEH) as a potential target to lessen the severity of strokes.

sEH is known to be involved in the detoxification of a broad range of structurally diverse compounds formed in the course of xenobiotic metabolism. Hammock's lab has been instrumental in discovering a number of other physiological processes that the enzyme is involved in, including the breakdown of epoxyeicosatrienoic (EET) acids. EETs are produced in the brain by astrocytes and play an important role in the regulation of cerebral blood flow.

In the current experiments, mice injected with an inhibitor of sEH had significantly less brain damage than non-treated mice 24 hours after undergoing middle cerebral artery occlusion. Cerebral blood flow rates were not different between the treated and untreated mice suggesting that sEH inhibition protects against ischemic injury through non-vascular mechanisms and also suggesting that sEH inhibition may be an effective treatment to reduce post-stroke brain damage. This finding is consistent with human genetics studies demonstrating that polymorphisms in the gene coding for sEH are linked to cardiovascular disease risk.

Citation: Zhang W, Koerner IP, Noppens R, Grafe M, Tsai HJ, Morisseau C, Luria A, Hammock BD, Falck JR, Alkayed NJ. Soluble epoxide hydrolase: a novel therapeutic target in stroke. J Cereb Blood Flow Metab. 2007 Dec;27(12):1931-40.