{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:45:06Z","timestamp":1783741506819,"version":"3.55.0"},"reference-count":62,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81571106"],"award-info":[{"award-number":["81571106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:p>Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprotective role of PFKFB3 in t-SCI. A compressive clip was introduced to establish the t-SCI model. Herein, we identified that PFKFB3 was extensively distributed in neurons, and PFKFB3 levels significantly increased and peaked 24 h after t-SCI. Additionally, knockdown of PFKFB3 inhibited glycolysis, accompanied by aggravated neuronal apoptosis and white matter injury, while pharmacological activation of PFKFB3 with meclizine significantly enhanced glycolysis, attenuated t-SCI-induced spinal cord injury, and alleviated neurological impairment. The PFKFB3 agonist, meclizine, activated cyclin-dependent kinase 1 (CDK1) and promoted the phosphorylation of p27, ultimately suppressing neuronal apoptosis. However, the neuroprotective effects of meclizine against t-SCI were abolished by the CDK1 antagonist, RO3306. In summary, our data demonstrated that PFKFB3 contributes robust neuroprotection against t-SCI by enhancing glycolysis and modulating CDK1-related antiapoptotic signals. Moreover, targeting PFKFB3 may be a novel and promising therapeutic strategy for t-SCI.<\/jats:p>","DOI":"10.1177\/0963689720950226","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T12:44:16Z","timestamp":1598359456000},"page":"096368972095022","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and \u201ccyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats"],"prefix":"10.1177","volume":"29","author":[{"given":"Liansheng","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Lenahan","sequence":"additional","affiliation":[{"name":"Burrell College of Osteopathic Medicine, Las Cruces, NM, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-0028","authenticated-orcid":false,"given":"Gao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,8,25]]},"reference":[{"key":"bibr1-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-0632-5"},{"key":"bibr2-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww039"},{"key":"bibr3-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.03.034"},{"key":"bibr4-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx217"},{"key":"bibr5-0963689720950226","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00098"},{"key":"bibr6-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.23.263"},{"key":"bibr7-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.05.014"},{"key":"bibr8-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.11.020"},{"key":"bibr9-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0736-y"},{"key":"bibr10-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70144-9"},{"key":"bibr11-0963689720950226","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.202933"},{"key":"bibr12-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.gep.2013.04.002"},{"key":"bibr13-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040752"},{"key":"bibr14-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3047"},{"issue":"20","key":"bibr15-0963689720950226","first-page":"5881","volume":"62","author":"Atsumi T","year":"2002","journal-title":"Cancer Res"},{"key":"bibr16-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(01)00014-6"},{"key":"bibr17-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-007-9471-7"},{"key":"bibr18-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024179"},{"key":"bibr19-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"bibr20-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12537"},{"key":"bibr21-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.10.006"},{"key":"bibr22-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.618157"},{"key":"bibr23-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.33"},{"key":"bibr24-0963689720950226","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00112"},{"issue":"4","key":"bibr25-0963689720950226","first-page":"337","volume":"43","author":"Murai H","year":"1991","journal-title":"No To Shinkei"},{"key":"bibr26-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.292"},{"key":"bibr27-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1177\/0091270011414575"},{"key":"bibr28-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1606"},{"key":"bibr29-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/srep25344"},{"key":"bibr30-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq464"},{"key":"bibr31-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.07.084"},{"key":"bibr32-0963689720950226","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00042"},{"key":"bibr33-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.07.023"},{"key":"bibr34-0963689720950226","doi-asserted-by":"publisher","DOI":"10.7150\/thno.25487"},{"key":"bibr35-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1433"},{"key":"bibr36-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(80)90515-4"},{"key":"bibr37-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27136"},{"key":"bibr38-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/sc.2015.208"},{"key":"bibr39-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-2092-9"},{"key":"bibr40-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.016816"},{"key":"bibr41-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1982.tb07039.x"},{"key":"bibr42-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.01.013"},{"key":"bibr43-0963689720950226","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.10.108"},{"key":"bibr44-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101426"},{"key":"bibr45-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2197-6"},{"key":"bibr46-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03406-9"},{"key":"bibr47-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201901589"},{"key":"bibr48-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14912"},{"key":"bibr49-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1101\/gad.889901"},{"key":"bibr50-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3231"},{"key":"bibr51-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-7678-9_3"},{"key":"bibr52-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2018.2082"},{"key":"bibr53-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104742"},{"key":"bibr54-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.02.007"},{"key":"bibr55-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313374"},{"key":"bibr56-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2018.1498082"},{"key":"bibr57-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.7689"},{"key":"bibr58-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2018.07.008"},{"key":"bibr59-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13918"},{"key":"bibr60-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400581"},{"key":"bibr61-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.9.1181"},{"key":"bibr62-0963689720950226","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54917-1"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720950226","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0963689720950226","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720950226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:38:10Z","timestamp":1777390690000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.1177\/0963689720950226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":62,"alternative-id":["10.1177\/0963689720950226"],"URL":"https:\/\/doi.org\/10.1177\/0963689720950226","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]}}}