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NR4A1 enhances neural survival following oxygen and glucose deprivation: An in vitro study

  • Guodong Xiao
    Affiliations
    Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215004, China
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  • Tao Sun
    Affiliations
    Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, 210002, China
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  • Cheng Songming
    Affiliations
    Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, 210002, China
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  • Yongjun Cao
    Correspondence
    Corresponding author at: Department of Neurology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Rd, Suzhou, Jiangsu Province, 215004, China. Tel.: +86 15052253917.
    Affiliations
    Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215004, China
    Search for articles by this author

      Abstract

      A worldwide epidemic of stroke is exacting a huge level of patient suffering and social cost. The ischemia damage to neural cells and the associated permanent neural function loss are central to the pathophysiology of stroke.
      In the current study, we were endeavored to identify NR4A1, an orphan nuclear receptor as a novel protector for neural cells in an in vitro neural ischemia model. Our results showed that oxygen and glucose deprivation (OGD) dramatically induced primary culture neural cell apoptosis and NR4A1 expression at both protein and mRNA level. Furthermore, hyperexpression or knock-down of NR4A1 significantly ameliorated or exacerbated OGD induced neural damage as manifested by decreased or increased apoptotic rates and key apoptotic protein expression respectively. As part of effort to identify the underlying mechanism, we also found that survivin is highly inducible following OGD and is required for NR4A1 action in this scenario.
      Our data seemed to be logical extensions of previous observations showing that NR4As are highly inducible following focal cerebral ischemia. Of note, our results also demonstrated that NR4A1 induction in this scenario may be functionally important as well and targeting NR4A1 protein can be intriguing as part of the effort to develop novel therapeutic strategies for neural protection after stroke.

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