Differences in neurological injury and functional deficit occur among individuals who suffer stroke. Recently, single nucleotide polymorphisms in the gene coding for human soluble epoxide hydrolase have been described. These polymorphisms result in multiple genetically-determined phenotypes and may contribute to differences in stroke outcome.  

Soluble epoxide hydrolase (sEH) is a fatty acid metabolizing enzyme that contributes to stroke injury. Our preliminary data suggest that sEH polymorphisms modify the level of the enzyme’s activity, and this change in sEH activity proportionately alters cell death in cultured neurons deprived of oxygen and glucose (simulated stroke). However, we do not know whether human sEH gene mutations affect brain injury following stroke in vivo. Our data also indicate that genetically unaltered sEH contributes to brain inflammation, which is known to significantly enhance cell death and infarct volume after stroke; but the exact causal mechanism is unclear.

In this study, we will use a rodent stroke model to determine whether human sEH mutations change histological and functional outcome after stroke. To further investigate the mechanism behind this expected effect, we hypothesize that sEH deletion reduces activation of microglia, the resident brain immune cells, after stroke by inhibiting the pro-inflammatory transcription factor nuclear factor (NF)-κB. Our findings will yield novel information about the genetic basis for individual vulnerability to stroke injury.

This research project is funded by the Medical Research Foundation at Oregon Health & Science University.