{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:36:56Z","timestamp":1788871016042,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T00:00:00Z","timestamp":1423785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["20080440806"],"award-info":[{"award-number":["20080440806"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Guandong Natural Science Foundation","doi-asserted-by":"publisher","award":["039191"],"award-info":[{"award-number":["039191"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2006AA090502"],"award-info":[{"award-number":["2006AA090502"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Summary<\/jats:title>\n \n Background<\/jats:title>\n \n Neuroactive steroids represent promising candidates for the treatment of neurological disorders. Our previous studies identified an endogenous steroid cholestane\u20103\n \u03b2<\/jats:italic>\n , 5\n \u03b1<\/jats:italic>\n , 6\n \u03b2<\/jats:italic>\n \u2010triol (Triol) as a novel neuroprotectant.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n We aimed to identify a potent candidate for stroke treatment through a screening of Triol analogs.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Hypoxia\u2010 and glutamate\u2010induced neuronal injury models\n in vitro,<\/jats:italic>\n middle cerebral artery occlusion (\n MCAO<\/jats:styled-content>\n )\u2010induced cerebral ischemia model\n in vivo,<\/jats:italic>\n fluorescein diacetate (\n FDA<\/jats:styled-content>\n ) for alive and propidium iodide (\n PI<\/jats:styled-content>\n ) for dead staining,\n LDH<\/jats:styled-content>\n assay, and calcium imaging techniques were used.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 24\u2010keto\u2010cholest\u20105\u2010en\u20103\n \u03b2<\/jats:italic>\n , 19\u2010diol (Diol) showed the most potent neuroprotective effect among the screened structurally related compounds.\n FDA<\/jats:styled-content>\n and\n PI<\/jats:styled-content>\n staining showed that Diol concentration dependently increased the survival rate of cerebellar granule neurons (\n CGN<\/jats:styled-content>\n s) challenged with glutamate or hypoxia, with an effective threshold concentration of 2.5\u00a0\n \u03bc<\/jats:italic>\n M. Consistently, the quantitative\n LDH<\/jats:styled-content>\n release assay showed the same concentration\u2010dependent protection in both models. Diol, at 10\u00a0\n \u03bc<\/jats:italic>\n M, potently decreased glutamate\u2010 and hypoxia\u2010induced\n LDH<\/jats:styled-content>\n release from 51.6 to 18.2% and 62.1 to 21.7%, respectively, which values are close to the normal\n LDH<\/jats:styled-content>\n release (~16\u201318%). Moreover, we found Diol effectively decreased\n MCAO<\/jats:styled-content>\n \u2010induced infarction volume in mice from ~23% to 7%, at a dose of 6\u00a0mg\/kg. We further explored the underlying mechanism and found that Diol attenuated\n NMDA<\/jats:styled-content>\n \u2010induced intracellular calcium ([Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n ) increase in cortical neurons, suggesting a negative modulatory effect on\n NMDA<\/jats:styled-content>\n receptor.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Taken together, we identified Diol as a potent neuroprotectant. It may represent a novel and promising neuroprotectant for stroke intervention.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.12378","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T08:25:37Z","timestamp":1423815937000},"page":"486-495","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of a Synthetic Steroid 24\u2010keto\u2010cholest\u20105\u2010en\u20103\n \u03b2<\/i>\n , 19\u2010diol as a Neuroprotectant"],"prefix":"10.1111","volume":"21","author":[{"given":"Min","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pharmacology Zhongshan Medical College Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai\u2010Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Zhongshan Medical College Sun Yat\u2010Sen University Guangzhou 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