{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:08:12Z","timestamp":1792804092683,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074003"],"award-info":[{"award-number":["82074003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174083"],"award-info":[{"award-number":["82174083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["51903246"],"award-info":[{"award-number":["51903246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20201196"],"award-info":[{"award-number":["BK20201196"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Many neurons undergo apoptosis after ischemic stroke. In the brain, neurogenesis has the potential for neuronal replacement and can be activated by external conditions to repair the injury. Crocetin (CRO), naturally extracted from the plant saffron, acts as a neuroprotective agent for ischemic stroke. However, the underlying mechanism remains unknown. In this work, the effect of CRO on neural stem cell (NSC) behaviors and subventricular zone neurogenesis is investigated. Initially, NSCs are incubated with different concentrations of CRO to detect the cell proliferation and differentiation in vitro. Second, ischemic stroke induced rats are treated with CRO using nimodipine (NMDP) as a comparison. The behavioral functions, infarcted volume, and apoptotic Nissl bodies of rats are noticeably improved after CRO\u2010treatment, comparable to those of NMDP. In addition, the increased regional cerebral blood flow and promoted neuronal differentiation are achieved by CRO\u2010treatment. Brain tissue examination shows significantly increased neuronal regeneration in the focal ischemic injury area. Meanwhile, the length of neurites is prolonged, indicating that CRO could potentially promote neurite extension to enhance cell\u2013cell communication. These findings demonstrate that CRO facilitated the neuronal differentiation of NSCs by activating subventricular zone neurogenesis in damaged cortex and striatum sites to repair ischemic stroke.<\/jats:p>","DOI":"10.1002\/adhm.202203132","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T18:03:40Z","timestamp":1680285820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Crocetin Regulates Functions of Neural Stem Cells to Generate New Neurons for Cerebral Ischemia Recovery"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhongqing","family":"Liu","sequence":"first","affiliation":[{"name":"College of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanchi","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China  Hefei Anhui 230026 China"},{"name":"CAS Key Laboratory of Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano Bionics Chinese Academy of Sciences  Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Hong","sequence":"additional","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China  Hefei Anhui 230026 China"},{"name":"CAS Key Laboratory of Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano Bionics Chinese Academy of Sciences  Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leisha","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China  Hefei Anhui 230026 China"},{"name":"CAS Key Laboratory of Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano Bionics Chinese Academy of Sciences  Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China  Hefei Anhui 230026 China"},{"name":"CAS Key Laboratory of Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano Bionics Chinese Academy of Sciences  Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-9403","authenticated-orcid":false,"given":"Guosheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Nano\u2010Tech and Nano\u2010Bionics University of Science and Technology of China  Hefei Anhui 230026 China"},{"name":"CAS Key Laboratory of Nano\u2010Bio Interface Suzhou Institute of Nano\u2010Tech and Nano Bionics Chinese Academy of Sciences  Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30962-X"},{"key":"e_1_2_9_1_2","first-page":"1985","volume":"351","author":"Ferriero D. M.","year":"2004","journal-title":"J. Med."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-020-00806-z"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.531632"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.191261"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2012.11.013"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000226651.04862.da"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00415"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.149"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-010814-015006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018820"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0963689717721230"},{"key":"e_1_2_9_6_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.07.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107695"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.03.041"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105963"},{"key":"e_1_2_9_8_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.05.042"},{"key":"e_1_2_9_8_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112426"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2020.1864279"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf802027a"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-018-0132-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5130"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X16666180321095705"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.07.002"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000196957.55928.ab"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30668-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.020711"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11870-x"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12069"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.141"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.10.036"},{"key":"e_1_2_9_18_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111709"},{"key":"e_1_2_9_18_4","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/727542"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.104"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1233"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24005"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1996.tb00875.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.159"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.04.010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2020.03.014"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.07.003"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9281"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.745683"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010021"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.11.019"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201705694"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22758-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202100027"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"},{"key":"e_1_2_9_29_2","first-page":"3445","volume":"9","author":"Fluri F.","year":"2015","journal-title":"Drug Des., Dev. Ther."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.146901"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.02.038"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202203132","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:36:57Z","timestamp":1759750617000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202203132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":52,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/adhm.202203132"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202203132","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]},"assertion":[{"value":"2022-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2203132"}}