{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:11:49Z","timestamp":1780377109999,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T00:00:00Z","timestamp":1590796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471257"],"award-info":[{"award-number":["81471257"]}],"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":["81873924"],"award-info":[{"award-number":["81873924"]}],"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":["BK20161283"],"award-info":[{"award-number":["BK20161283"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) results not only in gray matter damage, but also in severe white matter injury (WMI). Previous findings support hypoxic preconditioning (HP) could augment the efficacy of bone marrow stromal cell (BMSC) transplantation in a TBI mouse model. However, whether HP\u2010treated BMSCs (H\u2010BMSCs) could overcome remyelination failure after WMI is unclear, and the molecular mechanisms remain to be explored. Here, we focused on the therapeutic benefits of H\u2010BMSC transplantation for treating WMI, as well as its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro, BMSCs were incubated at passage 4 in the hypoxic preconditioning (1.0% oxygen) for 8\u00a0hr. In vivo, a TBI mouse model was established, and DMEM cell culture medium (control), normal cultured BMSCs (N\u2010BMSCs), or H\u2010BMSCs were transplanted to mice 24\u00a0hr afterward. Neurobehavioral function, histopathological changes, and oligodendrogenesis were assessed for up to 35\u00a0days post\u2010TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the control group, improvement of cognitive functions and smaller lesion volumes was observed in the two BMSC\u2010transplanted groups, especially the H\u2010BMSC group. H\u2010BMSC transplantation resulted in a greater number of neural\/glial antigen 2 (NG2)\u2013positive and adenomatous polyposis coli (APC)\u2013positive cells than N\u2010BMSC transplantation in both the corpus callosum and the striatum. In addition, we observed that the expression levels of hypoxia\u2010inducible factor\u20101a (HIF\u20101\u03b1), phosphorylated mechanistic target of rapamycin (p\u2010mTOR), and vascular endothelial growth factor (VEGF) were all increased in H\u2010BMSC\u2013transplanted mice. Furthermore, the mTOR pathway inhibitor rapamycin attenuated the impact of HP both in vivo and in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results provided mechanistic evidences suggesting that HP\u2010treated BMSCs promoted remyelination partly by modulating the pro\u2010survival mTOR\/HIF\u20101\u03b1\/VEGF signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.1675","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T02:45:10Z","timestamp":1590893110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hypoxic preconditioning enhances the differentiation of bone marrow stromal cells into mature oligodendrocytes via the mTOR\/HIF\u20101\u03b1\/VEGF pathway in traumatic brain injury"],"prefix":"10.1002","volume":"10","author":[{"given":"Xiaoyu","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"},{"name":"Department of Emergency Affiliated Hospital of Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqiang","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-8534","authenticated-orcid":false,"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neuropharmacology Institute of Special Environmental Medicine and Co\u2010innovation Center of Neuroregeneration Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/389520"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00885"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120226"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0445-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04329.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2004.06.009"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2014.09.026"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2016.12.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2015.04.010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.12.016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.143"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1210-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1179\/1743132812Y.0000000151"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.19-3-219"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611782200"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13102"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25931"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.07.007"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0202-2"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.3899"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00038"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443031"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.03.011"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.09.033"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0157-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2011.1939"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501441112"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215600548"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.12.017"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.113"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbrb3.1675","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1675","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/brb3.1675","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.1675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T05:16:49Z","timestamp":1693631809000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.1675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,30]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/brb3.1675"],"URL":"https:\/\/doi.org\/10.1002\/brb3.1675","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BRB3.1675\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BRB3.1675\/v3\/response1","asserted-by":"object"}]},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"value":"2162-3279","type":"print"},{"value":"2162-3279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,30]]},"assertion":[{"value":"2019-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01675"}}