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Therefore, we aimed to investigate therapeutic effect of SFN in the treatment of DAI and the ability of SFN to reduce oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 3\u2010(4,5\u2010dimethyl\u20102\u2010thiazolyl)\u20102,5\u2010diphenyl\u20102H\u2010tetrazolium bromide (MTT) assay was used to observe the effects of H<jats:sub>2<\/jats:sub>O\n<jats:sub>2<\/jats:sub> and SFN on cell viability. Fluorometric assay, Western blot analysis, and flow cytometry were conducted to validate the protective role of SFN in an animal model of DAI. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in DAI rats treated by SFN, while Western blot, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were carried out to verify the effect of SFN in different animal groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cell viability was reduced by H<jats:sub>2<\/jats:sub>O\n<jats:sub>2<\/jats:sub> in a dose\u2010dependent manner, while the treatment by SFN significantly promoted cell growth. Meanwhile the administration of SFN effectively reduced the levels of caspase\u20103\/poly(ADP\u2010ribose) polymerase (PARP) activity increased by the H\n<jats:sub>2<\/jats:sub>O\n<jats:sub>2<\/jats:sub> treatment, indicating that the protective effect of SFN could be mediated by its ability to suppress caspase\u20103 activation and PARP cleavage. In addition, the SFN treatment reduced the intracellular reactive oxygen species (ROS) generation induced by H\n<jats:sub>2<\/jats:sub>O\n<jats:sub>2<\/jats:sub>. Moreover, the MDA levels of SOD\/GPx activity in various rat groups showed the protective effects of SFN in DAI rats. It is suspected that the protective effect of SFN was exerted via the activation of the Nrf2\/HO\u20101 signaling pathway. In this study, DAI and DAI\u2009+\u2009phosphate\u2010buffered saline (PBS) groups also showed the presence of more TUNEL\u2010positive cells compared with the sham\u2010operated group, while the SFN treatment reduced the extent of neuronal apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>By activating the Nrf2\/HO\u20101 signaling pathway and reducing the activity of caspase\u20103, SFN reduces the apoptosis of neurons in brain trauma\u2010induced DAI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.29203","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T09:05:06Z","timestamp":1561367106000},"page":"430-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Sulforaphane administration alleviates diffuse axonal injury (DAI) via regulation signaling pathway of NRF2 and HO\u20101"],"prefix":"10.1002","volume":"121","author":[{"given":"Dong\u2010Mei","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science Jiangsu Normal University Xuzhou China"},{"name":"College of Health Sciences Jiangsu Normal University Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Medicine and Life Sciences Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao\u2010Hua","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science Jiangsu Normal University Xuzhou China"},{"name":"College of Health Sciences Jiangsu Normal University 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