{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T14:17:16Z","timestamp":1784989036458,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T00:00:00Z","timestamp":1426032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R21 NS080799"],"award-info":[{"award-number":["R21 NS080799"]}]},{"name":"NIH","award":["R01 NS086890"],"award-info":[{"award-number":["R01 NS086890"]}]},{"name":"NIH","award":["R01 ES017462"],"award-info":[{"award-number":["R01 ES017462"]}]},{"name":"NIH","award":["P01 HD29587"],"award-info":[{"award-number":["P01 HD29587"]}]},{"name":"La Jolla Interdisciplinary Neuroscience Center Core Grant","award":["P30 NS076411"],"award-info":[{"award-number":["P30 NS076411"]}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cyanide is a life\u2010threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome <jats:italic>c<\/jats:italic> oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed\u2010onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide\u2010induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide\u2010induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> protective effect of carnosic acid (<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>), a pro\u2010electrophilic compound found in the herb rosemary. <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> crosses the blood\u2013brain barrier to up\u2010regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> exerts neuroprotective effects on cyanide\u2010induced brain damage in cultured rodent and human\u2010induced pluripotent stem cell\u2010derived neurons <jats:italic>in\u00a0vitro<\/jats:italic>, and <jats:italic>in\u00a0vivo<\/jats:italic> in various brain areas of a non\u2010Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain.\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\/jnc13074-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nCyanide, a potential bioterrorist agent, can produce a chronic delayed\u2010onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic> models through activation of the Nrf2\/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid\u2010derived 2)\u2010like 2).\n<\/jats:p>","DOI":"10.1111\/jnc.13074","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T13:53:03Z","timestamp":1424267583000},"page":"898-908","source":"Crossref","is-referenced-by-count":59,"title":["Protection from cyanide\u2010induced brain injury by the Nrf2 transcriptional activator carnosic acid"],"prefix":"10.1111","volume":"133","author":[{"given":"Dongxian","family":"Zhang","sequence":"first","affiliation":[{"name":"Neuroscience and Aging Research Center Sanford\u2010Burnham Medical Research Institute La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lee","sequence":"additional","affiliation":[{"name":"Neuroscience and Aging Research Center Sanford\u2010Burnham Medical Research Institute La Jolla California 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