{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:04Z","timestamp":1787014024802,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T00:00:00Z","timestamp":1474934400000},"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":["81201979"],"award-info":[{"award-number":["81201979"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2017,2]]},"abstract":"Summary<\/jats:title>\n \n Aims<\/jats:title>\n \n Traumatic brain injury (\n TBI<\/jats:styled-content>\n ) is induced by complex primary and secondary mechanisms that give rise to cell death, inflammation, and neurological dysfunction. Understanding the mechanisms that drive neurological damage as well as those that promote repair can guide the development of therapeutic drugs for\n TBI<\/jats:styled-content>\n . Kruppel\u2010like factor 4 (\n KLF<\/jats:styled-content>\n 4) has been reported to negatively regulate axon regeneration of injured retinal ganglion cells (\n RGC<\/jats:styled-content>\n s) through inhibition of\n JAK<\/jats:styled-content>\n \u2010\n STAT<\/jats:styled-content>\n 3 signaling. However, the role of\n KLF<\/jats:styled-content>\n 4 in\n TBI<\/jats:styled-content>\n remains unreported. Reactive oxygen species (\n ROS<\/jats:styled-content>\n )\u2010induced neuronal death is a pathophysiological hallmark of\n TBI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this study, we used H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n \u2010treated\n RGC<\/jats:styled-content>\n s\n in vitro<\/jats:italic>\n and the optic nerve crush model\n in vivo<\/jats:italic>\n to simulate neuronal damage in\n TBI<\/jats:styled-content>\n . The function of\n KLF<\/jats:styled-content>\n 4 in\n RGC<\/jats:styled-content>\n survival and axon regeneration in these models was investigated. In addition, the effects of\n KLF<\/jats:styled-content>\n 4 knockdown on neuronal damage after a brain impact that mimics moderate\n TBI<\/jats:styled-content>\n were studied.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The results show that H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n induces p53\u2010dependent apoptosis of\n RGC<\/jats:styled-content>\n s\n in vitro<\/jats:italic>\n through upregulation of\n KLF<\/jats:styled-content>\n 4. Additionally,\n KLF<\/jats:styled-content>\n 4 knockdown\n in vivo<\/jats:italic>\n significantly enhances\n CNTF<\/jats:styled-content>\n \u2010induced axon regeneration of\n RGC<\/jats:styled-content>\n s after optic nerve crush, and more importantly, prevents neuronal damage after a moderate brain impact in rats. Our Western blot analysis and immunoprecipitation assay results indicate that these effects of\n KLF<\/jats:styled-content>\n 4 knockdown are mediated by the p53 and\n JAK<\/jats:styled-content>\n \u2010\n STAT<\/jats:styled-content>\n 3 pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings provide evidence that\n KLF<\/jats:styled-content>\n 4 plays an important role in the pathophysiology of\n TBI<\/jats:styled-content>\n . Blocking\n KLF<\/jats:styled-content>\n 4 may be a potential therapeutic strategy for the treatment of\n TBI<\/jats:styled-content>\n , either alone or in combination with agents that target complementary mechanisms.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.12633","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T04:43:19Z","timestamp":1474951399000},"page":"106-118","source":"Crossref","is-referenced-by-count":53,"title":["KLF<\/scp>\n 4 Knockdown Attenuates\n TBI<\/scp>\n \u2010Induced Neuronal Damage through p53 and\n JAK<\/scp>\n \u2010\n STAT<\/scp>\n 3 Signaling"],"prefix":"10.1111","volume":"23","author":[{"given":"Da\u2010Ming","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,27]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"CDC.Injury Prevention & Control: Traumatic Brain 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