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Research Article| Volume 319, ISSUE 1-2, P117-123, August 15, 2012

Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats

  • Author Footnotes
    1 These authors contributed equally to this study.
    Bin Wang
    Footnotes
    1 These authors contributed equally to this study.
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Author Footnotes
    1 These authors contributed equally to this study.
    Lin Sun
    Footnotes
    1 These authors contributed equally to this study.
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Ye Tian
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Zhanying Li
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China

    Department of Neurosurgery, Kailuan Hospital, North China Coal Medical School, Tangshan, PR China
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  • Huijie Wei
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Dong Wang
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Zhuo Yang
    Affiliations
    School of Medicine, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, PR China
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  • Jieli Chen
    Affiliations
    Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA
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  • Jianning Zhang
    Correspondence
    Correspondence to: J. Zhang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China. Tel./fax: +86 02260814359.
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
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  • Rongcai Jiang
    Correspondence
    Correspondence to: R. Jiang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China. Tel./fax: +86 02260817449.
    Affiliations
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    Tianjin Neurological Institute, Tianjin, PR China

    Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, PR China

    Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, PR China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this study.

      Abstract

      Circulating endothelial progenitor cells (EPCs) play an important role in angiogenesis and vasculogenesis. Statins administered promote functional improvement in rats, independent of their capability to lower cholesterol. Whether statin treatment regulates circulating EPCs after traumatic brain injury (TBI) has not been investigated. We hypothesized that atorvastatin increases circulating EPCs and promotes angiogenesis in TBI rats. Wistar rats (20 months old) were subjected to TBI and treated with or without atorvastatin (orally administered, 1 mg/kg/day) starting 1 h after TBI and then daily for 14 consecutive days. Long term potentiation (LTP) in the cornu ammonis1 of the hippocampus as well as the Modified Neurological Severity Score (mNSS) and the Morris Water Maze (MWM) functional tests were performed. Blood circulating EPCs were identified by flow cytometry. Rats were sacrificed 25 days after TBI. vWF and CD31 immunostaining was performed. We found that atorvastatin administration significantly induced angiogenesis and increased circulating EPC levels as well as improved functional recovery when compared with non-treatment TBI-control rats (P<0.05). The circulating EPC level is correlated with vascular density (r=0.878, P <0.05) and CD31 positive cell number in the injured brain (r=0.921, P <0.05). The results suggest that increasing circulating EPCs with atorvastatin treatment may contribute to the observed increase in angiogenesis and improved functional outcome after TBI.

      Keywords

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