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Astrocytes can release protective neurotrophic factors, such as vascular endothelial growth factor (VEGF). We found that addition of sEH inhibitors to rat cultured astrocytes immediately after oxygen\u2010glucose deprivation (OGD) markedly increased VEGF concentration in the medium 48\u00a0h later and the effect was blocked by an EET antagonist. The sEH inhibitors increased EET concentrations to levels capable of increasing VEGF. When the sEH inhibitors were removed from the medium at 48\u00a0h, the increase in VEGF persisted for an additional 48\u00a0h. Neurons exposed to OGD and subsequently to astrocyte medium previously conditioned with OGD plus sEH inhibitors showed increased phosphorylation of their VEGF receptor\u20102, less TUNEL staining, and increased phosphorylation of Akt, which was blocked by a VEGF receptor\u20102 antagonist. Our findings indicate that sEH inhibitors, applied to cultured astrocytes after an ischemia\u2010like insult, can increase VEGF secretion. The released VEGF then enhances Akt\u2010enabled cell survival signaling in neurons through activation of VEGF receptor\u20102 leading to less neuronal cell death. These results suggest a new strategy by which astrocytes can be leveraged to support neuroprotection.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13933-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13933","type":"journal-article","created":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T22:36:58Z","timestamp":1482359818000},"page":"814-825","source":"Crossref","is-referenced-by-count":28,"title":["Inhibition of soluble epoxide hydrolase augments astrocyte release of vascular endothelial growth factor and neuronal recovery after oxygen\u2010glucose deprivation"],"prefix":"10.1111","volume":"140","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore Maryland"},{"name":"Department of Anesthesiology Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin Sing Stephen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology and UCD Comprehensive Cancer Center University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Hammock","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology and UCD Comprehensive Cancer Center University of California Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debebe","family":"Gebremedhin","sequence":"additional","affiliation":[{"name":"Department of Physiology and the Cardiovascular Research Center Medical College of Wisconsin Milwaukee Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Physiology and the Cardiovascular Research Center Medical College of Wisconsin Milwaukee Wisconsin"},{"name":"Clement J. Zablocki VA Medical Center Milwaukee Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Koehler","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sapirstein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06613"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216514110"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1523\/JNEUROSCI.23-05-01678.2003","article-title":"Metabotropic glutamate receptor activation enhances the activities of two types of Ca2\u00a0+\u00a0 \u2010activated K+ channels in rat hippocampal astrocytes","volume":"23","author":"Gebremedhin D.","year":"2003","journal-title":"J. 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