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The roles and the kinetics of gp91 phox after traumatic brain injury in mice

Research Project

Project/Area Number 20592128
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

DOHI Kenji  Showa University, 医学部, 講師 (20301509)

Co-Investigator(Kenkyū-buntansha) ARUGA Tohru  昭和大学, 医学部, 教授 (40266086)
SHIODA Seiji  昭和大学, 医学部, 教授 (80102375)
MORIKAWA Kentarou  昭和大学, 医学部, 助教 (20317720)
YOUFU Sachiko  昭和大学, 医学部, 普通研究性 (00398695)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords集中治療医学 / 重症頭部外傷 / 脳損傷 / 治療 / NADPH / 酸化ストレス / フリーラジカル / 頭部外傷 / マウス / 脳保護 / NOX / gp91 / マイクログリア
Research Abstract

INTRODUCTION :
We hypothesized that gp91phox (NOX2), a subunit of NADPH oxidase, generates superoxide anion (O2-) and has a major causative role in traumatic brain injury (TBI). To evaluate the functional role of gp91phox and reactive oxygen species (ROS) on TBI, we carried out controlled cortical impact in gp91phox knockout mice (gp91phox-/-). We also used a microglial cell line to determine the activated cell phenotype that contributes to gp91phox generation.
METHODS :
Unilateral TBI was induced in gp91phox-/- and wild-type (Wt) mice (C57/B6J) (25-30 g). The expression and roles of gp91phox after TBI were investigated using immunoblotting and staining techniques. Levels of O2- and peroxynitrite were determined in situ in the mouse brain. The activated phenotype in microglia that expressed gp91phox was determined in a microglial cell line, BV-2, in the presence of IFNgamma or IL-4.
RESULTS :
Gp91phox expression increased mainly in amoeboid-shaped microglial cells of the ipsilateral hemisphere of Wt mice after TBI. The contusion area, number of TUNEL-positive cells, and amount of O2- and peroxynitrite metabolites produced were less in gp91phox-/- mice than in Wt. In the presence of IFNgamma, BV-2 cells had increased inducible nitric oxide synthase and nitric oxide levels, consistent with a classical activated phenotype, and drastically increased expression of gp91phox.
CONCLUSIONS :
Classical activated microglia promote ROS formation through gp91phox and have an important role in brain damage following TBI. Modulating gp91phox and gp91phox -derived ROS may provide a new therapeutic strategy in combating post-traumatic brain injury.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (17 results)

All 2010 2008

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (11 results)

  • [Journal Article] Novel free radical monitoring in patients with neurological emergency diseases.2010

    • Author(s)
      Dohi K, Satoh K, Nakamachi T, Ohtaki H, Yofu S, Nakamura S, Shioda S, Aruga T
    • Journal Title

      Acta Neurochir Suppl 106

      Pages: 315-319

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury2010

    • Author(s)
      Dohi K, Ohtaki H, Nakamachi T, Yofu S, Satoh K, Miyamoto K, Song D, Tsunawaki S, Shioda S, Aruga T
    • Journal Title

      Journal of Neuro inflammation 7

      Pages: 41-52

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel free radical monitoring in patients with neurological emergency diseases.2010

    • Author(s)
      Dohi K., Satoh K, Nakamachi T., Ohtaki H., Yofu S, Nakamura S., Shioda S., Aruga T.
    • Journal Title

      Acta Neurochir Suppl

      Volume: 106 Pages: 315-319

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury.2010

    • Author(s)
      Dohi K., Ohtaki H., Nakamachi T., Yofu S, Satoh K., Miyamoto K, Song D., Tsunawaki S, Shioda S., Aruga T
    • Journal Title

      Journal of Neuroinflammation

      Volume: 7 Pages: 41-52

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel free radical monitoring in patients with neurological emergency diseases2010

    • Author(s)
      Dohi K.Satoh K.Nakamachi T.Ohtaki H.Yofu S.Nakamura S.Shioda S.Aruga T
    • Journal Title

      Acta Neurochir Suppl 106

      Pages: 315-319

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 頭部外傷と酸化ストレス : フリーラジカルモニタリングとその臨床応用について2008

    • Author(s)
      土肥謙二, 他3名
    • Journal Title

      神経外傷 31

      Pages: 1-8

    • NAID

      10031136378

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 頭部外傷後のcytotoxic microgliaにおけるgp91phoxの発現と役割2010

    • Author(s)
      土肥謙二, 大滝博和, 佐藤和恵, 中町智哉, 養父佐知子, 宋丹丹, 村上朋恵, 宮本和幸, 塩田清二, 有賀徹
    • Organizer
      第15回日本解剖学会総会
    • Place of Presentation
      岩手
    • Year and Date
      2010-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 頭部外傷後のcytotoxic microgliaにおけるgp91phoxの発現と役割2010

    • Author(s)
      土肥謙二,大滝博和,佐藤和恵,中町智哉,養父佐知子,宋丹丹,村上朋恵,宮本和幸,塩田清二,有賀徹
    • Organizer
      第115回日本解剖学会総会
    • Place of Presentation
      盛岡(昭和大学 医学部救急医学講座)
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel free radical monitoring in patients with neurological emergency diseases2010

    • Author(s)
      Dohi K, Satoh K, Nakamachi T, Ohtaki H, Yofu S, Nakamura S, Shioda S, Aruga T
    • Organizer
      Oxygen Club California 2010
    • Place of Presentation
      Santa Barbala、USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel free radical monitoring in patients with neurological emergency diseases2010

    • Author(s)
      Dohi K, Satoh K, Nakamachi T, Ohtaki H, Yofu S, Nakamura S, Shioda S, Aruga T
    • Organizer
      10th INTERNATIONAL CONGRESS OF NEUROIMMUNOLOGY 2010
    • Place of Presentation
      Barcelona、Spain
    • Related Report
      2010 Final Research Report
  • [Presentation] gp9lphox produced superoxide radical in classical activated microglia and contributes to the severity of traumatic brain injury in mouse2010

    • Author(s)
      Dohi K, Shioda S, Ohtaki H, 他7名
    • Organizer
      Oxygen Club of California 2010 World Congress
    • Place of Presentation
      Santa Barbara, CA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脳低温療法における酸化ストレスのモニタリングと動態2008

    • Author(s)
      土肥謙二
    • Organizer
      第36回日本救急医学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] 実験的頭部外傷におけるスーパーオキシドラジカル産生におけるgp91phoxの動態と役割2008

    • Author(s)
      土肥謙二
    • Organizer
      第67回日本脳神経外科学会総会
    • Place of Presentation
      盛岡
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 頭部外傷におけるgp91phoxの動態と機能について2008

    • Author(s)
      土肥謙二
    • Organizer
      第61回日本酸化ストレス学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-06-19
    • Related Report
      2008 Annual Research Report
  • [Presentation] 脳損傷におけるgp91phox/NOXの発言とその機能2008

    • Author(s)
      土肥 謙二・佐藤 和恵・養父佐知子・中町智哉・森川健太郎・三原結子・塩田清二・有賀徹
    • Organizer
      第31回日本神経外傷学会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] 頭部外傷におけるgp91phoxの動態と機能について2008

    • Author(s)
      土肥謙二・佐藤和恵・中町智哉・養父佐知子・森川健太郎・塩田清二・有賀徹
    • Organizer
      第61回日本酸化ストレス学会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] 実験的頭部外傷におけるスーパーオキシドラジカル産生におけるgp91phoxの起動と役割2008

    • Author(s)
      土肥謙二
    • Organizer
      第67回日本脳神経外科学会
    • Place of Presentation
      盛岡
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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