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However, the mechanisms underlying its beneficial effects remain poorly defined. The present study tests the hypothesis that <jats:styled-content style=\"fixed-case\">SAC<\/jats:styled-content> attenuates ischemic neuronal injury by activating the nuclear factor erythroid\u20102\u2010related factor 2 (Nrf2)\u2010dependent antioxidant response in both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models. Our findings demonstrate that <jats:styled-content style=\"fixed-case\">SAC<\/jats:styled-content> treatment resulted in an increase in Nrf2 protein levels and subsequent activation of antioxidant response element pathway genes in primary cultured neurons and mice. Exposure of primary neurons to <jats:styled-content style=\"fixed-case\">SAC<\/jats:styled-content> provided protection against oxygen and glucose deprivation\u2010induced oxidative insults. In wild\u2010type (Nrf2<jats:sup>+\/+<\/jats:sup>) mice, systemic administration of <jats:styled-content style=\"fixed-case\">SAC<\/jats:styled-content> attenuated middle cerebral artery occlusion\u2010induced ischemic damage, a protective effect not observed in Nrf2 knockout (Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Taken together, these findings provide the first evidence that activation of the Nrf2 antioxidant response by <jats:styled-content style=\"fixed-case\">SAC<\/jats:styled-content> is strongly associated with its neuroprotective effects against experimental stroke and suggest that targeting the Nrf2 pathway may provide therapeutic benefit for the treatment of stroke.\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\/jnc12986-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>The transcription factor Nrf2 is involved in cerebral ischemic disease and may be a promising target for the treatment of stroke. We provide novel evidence that SAC confers neuroprotection against ischemic stroke by activating the antioxidant Nrf2 signaling pathway. ARE, antioxidant response element; GCLC, glutathione cysteine ligase regulatory subunit; GCLM, glutathione cysteine ligase modulatory subunit; HO\u20101, heme oxygenase\u20101; JNK, c\u2010Jun N\u2010terminal kinase; Keap1, Kelch\u2010like ECH\u2010associated protein 1; Maf, musculoaponeurotic fibrosarcoma; Nrf2, nuclear factor erythroid\u20102\u2010related factor 2; SAC, <jats:italic>S<\/jats:italic>\u2010allyl cysteine; ROS, reactive oxygen species.<\/jats:p>","DOI":"10.1111\/jnc.12986","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T07:32:14Z","timestamp":1415863934000},"page":"298-308","source":"Crossref","is-referenced-by-count":94,"title":["<i>S<\/i>\u2010allyl cysteine activates the Nrf2\u2010dependent antioxidant response and protects neurons against ischemic injury <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1111","volume":"133","author":[{"given":"Huanying","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth G.","family":"Perez","sequence":"additional","affiliation":[{"name":"Texas Tech University Health Science Center El Paso Paul L. 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