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Protective Effects of Therapeutic Hypothermia in Severe traumatic Brain Injured Patients Evaluated by Large scale Proteome Analyses in Cerebrospinal Fluid

Research Project

Project/Area Number 18390480
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionYamaguchi University

Principal Investigator

MAEKAWA Tsuyoshi  Yamaguchi University, Graduate School of Medicine, Professor (60034972)

Co-Investigator(Kenkyū-buntansha) IZUMI Tomonori  Yamaguchi University, Graduate School of Medicine, Associate Professor (00261694)
KASAOKA Shunji  Yamaguchi University, Graduate School of Medicine, Associate Professor (90243667)
TSURUTA Ryosuke  Yamaguchi University, University Hospital, Associate Professor (30263768)
ODA Yasutaka  Yamaguchi University, University Hospital, Assistant Professor (40397998)
KANEKO Tadashi  Yamaguchi University, University Hospital, Assistant Professor (50362372)
小泉 博靖  山口大学, 医学部附属病院, 助手 (40423389)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,500,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥12,600,000 (Direct Cost: ¥12,600,000)
Keywordssevere traumatic brain injury / Cerebrospinal fluid / proteome / high performance liquid chromatography / mass spectrometry / brain protection / therapeutic mild hypothermia / candidate proteins / 網羅的蛋白質解析 / 質量分析機 / 候補蛋白質
Research Abstract

The outcome of severe traumatic brain injury (TBI) patients is poor. We carry out the outcome improvement strategy for severe TBI patients (Glasgow Coma Scale score 4 to 8) by the therapeutic mild hypothermia treatment since 2002. These patients were randomized in two groups, i.e, normothermia group (NT, 35.5-37.0℃) and mild hypothermia group (HT, 32.0-34.0℃). Neurological outocome was evaluated by Glasgow Outcome Scale, 6 months later. The part of the results of intermediate analyses is reported. Among these patients, we measured various cytokine in cerebrospinal fluid (CSF) by beads array method to choose appropriate CSF samples in 2006. In addition, we established large-scale protein identification method in the exhaustive proteome analysis in human CSF.
To identify proteins associated with pathologic states of the acute brain injury and/or the hypothermia treatment, we performed large-scale analyses of CSF proteins using a two dimensional liquid chromatography/tandem mass spectromet … More ry system in fiscal year 2007. A total of 235 proteins, including 167 proteins with quantitative values, were identified in a mixture of CSF samples from a single NT, a single HT, and 13 Ctrl patients. Major subcellular localizations assigned to these proteins were "extracellular (52%)", "plasma membrane (19%)", and "cytoplasm (12%)", and the list of identified proteins were cataloged together with various types of biological information. Typical CSF proteins such as cystatin C did not show quantitative changes among three patient groups, whereas 84 proteins increased and 16 proteins decreased in NT, and 65 proteins increased and 19 proteins decreased in HT. Higher levels of glial fibrillary acidic protein and significantly lower levels of chromogranin A in both NT and HT, higher levels of acute-phase proteins, adhesion molecules, and extracellular matrix proteins in NT, and suppression of these NT-specific changes in HT suggested damages of the central nervous tissue and the up-regulation of inflammatory responses that could be suppressed partially by the hypothermia treatment in the pathologic state of the acute brain injury. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007

All Presentation (13 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Presentation] Proteomic characterization of cerebrospinal fluid reveals a protein subset associated with anoxic insult after cardiopulmonary resuscitation2008

    • Author(s)
      Yasutaka Oda
    • Organizer
      37th Critical Care Congress
    • Place of Presentation
      Hawaii Convention Center (Honolulu, Hawaii, USA)
    • Year and Date
      2008-02-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomic characterization of cerebrospinal fluid revels a protein subset associated with anoxic insult after cardiopulmonary resuscitation2008

    • Author(s)
      Yasutaka, Oda
    • Organizer
      37th Critical Care Congress
    • Place of Presentation
      Hawaii Convention Center, Honolulu, Hawaii, USA
    • Year and Date
      2008-02-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomic characterization of cerebrospinal fluid reveals a protein subset associated with anoxic insult after cardiopulmonary resuscitation2008

    • Author(s)
      Yasutaka Oda
    • Organizer
      37th Critical Care Congress
    • Place of Presentation
      Hawaii Convention Center(Honolulu,Hawaii,USA)
    • Year and Date
      2008-02-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] iTRAQ試薬を利用した脳脊髄液蛋白質の大規模定量解析2007

    • Author(s)
      泉 友則
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 心肺停止蘇生後患者における脳脊髄液の病態プロテオーム解析神経学的予後予測マーカー群の同定2007

    • Author(s)
      小田 泰崇
    • Organizer
      第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Large-scale and quantitative analysis of Cerebrospinal fluid proteins using iTRAQ reagent2007

    • Author(s)
      Tomonori, Izumi
    • Organizer
      The 30th Annual Meeting of the Molecular Biology Society of Japan, The 80th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomics analysis of cerebral fluid from patients with cardiopulmonary resuscitation2007

    • Author(s)
      Yasutaka, Oda
    • Organizer
      The 30th Annual Meeting of the Molecular Biology Society of Japan, The 80th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new bioinformatics tool for rapid screening and visualization of largescale quantitative proteome analysis2007

    • Author(s)
      Teppei Yamashita
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEX Convention Center (Seoul, Korea)
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomics analysis of cerebrospinal fluid from patients with cardiopulmonary resuscitation2007

    • Author(s)
      Tomonori Izumi
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEX Convention Center (Seoul, Korea)
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new bioinformatics tool for rapid screening and visualization of large-scale quantitative proteome analysis a2007

    • Author(s)
      Tappei, Yamashita
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEC Center, Seoul, Kore
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomics analysis of cerebral fluid from patients with cardiopulmonary resuscitation2007

    • Author(s)
      Tomonori, Izumi
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEC Center, Seoul, Korea
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new bioinformatics tool for rapid screening and visualization of largescale quantitative Proteome analysis.2007

    • Author(s)
      Teppei Yamashita,
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEX Convention Center(Seoul,Korea)
    • Year and Date
      2007-10-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] Proteomics analysis of cerebrospinal fluid from patients with cardidpulmonary resuscitation2007

    • Author(s)
      Tomonori Izumi
    • Organizer
      HUPO 6th Annual World Congress
    • Place of Presentation
      COEX Convention Center(Seoul,Korea)
    • Year and Date
      2007-10-09
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 急性中枢神経障害の予後判定方法2008

    • Inventor(s)
      前川 剛志
    • Industrial Property Rights Holder
      山口大学
    • Industrial Property Number
      2007-091600
    • Filing Date
      2008-03-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Overseas
  • [Patent(Industrial Property Rights)] 急性中枢神経障害の早期予後予測用抗体2007

    • Inventor(s)
      前川 剛志
    • Industrial Property Rights Holder
      山口大学
    • Filing Date
      2007-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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