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Fas\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>95 mediates apoptotic cell death in response to external stimuli. In mature neurons, Fas\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>95 signaling is modulated by Fas\u2010apoptotic inhibitory molecule 2 (Faim2), which reduces cell death in animal models of stroke, meningitis, and Parkinson disease. Erythropoietin (<jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content>) has been studied as a therapeutic strategy in ischemic stroke. Erythropoietin stimulates the phosphatidylinositol\u20103 kinase\/Akt (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt) pathway, which regulates Faim2 expression. Therefore, up\u2010regulation of Faim2 may contribute to neuroprotection by <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content>. Male Faim2\u2010deficient mice (Faim2<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type littermates (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) were subjected to 30\u00a0min of middle cerebral artery occlusion (<jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content>o) followed by 72\u00a0h of reperfusion. <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content> was applied before (30\u00a0min) and after (24 and 48\u00a0h) <jats:styled-content style=\"fixed-case\">MCA<\/jats:styled-content>o. In <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice application of <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content> at a low dose (5000\u00a0U\/kg) significantly reduced stroke volume, whereas treatment with high dose (90\u00a0000\u00a0U\/kg) did not. In Faim2<jats:sup>\u2212\/\u2212<\/jats:sup> animals administration of low\u2010dose <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content> did not result in a significant reduction in stroke volume. Faim2 expression as measured by quantitative reverse transcription polymerase chain reaction (<jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>) increased after low\u2010dose <jats:styled-content style=\"fixed-case\">EPO<\/jats:styled-content> but not with high dose. An extensive phenotyping including analysis of cerebral vessel architecture did not reveal confounding differences between the genotypes. In human post\u2010mortem brain Faim2 displayed a differential expression in areas of penumbral ischemia. Faim2 up\u2010regulation may contribute to the neuroprotective effects of low\u2010dose erythropoietin in transient brain ischemia. The dose\u2010dependency may explain mixed effects of erythropoietin observed in clinical stroke trials.<\/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\/jnc14296-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14296","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T08:40:41Z","timestamp":1515573641000},"page":"258-270","source":"Crossref","is-referenced-by-count":20,"title":["Faim2 contributes to neuroprotection by erythropoietin in transient brain 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