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

• Project/Area Number: 18591989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Showa University
• Principal Investigator: DOHI Kenji Showa University, School of Medicine, Associate professor (20301509)
• Co-Investigator(Kenkyū-buntansha): ARUGA Toru Showa University, School of Medicine, Professor (40266086) ; SHIODA Seiji Showa University, School of Medicine, Professor (80102375) ; YOFU Sachiko Showa University, School of Medicine, Researcher (00398695) ; SATOH Kazue Showa University, School of Medicine, Professor (90053941)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: free radical / neurotrauma / oxidative stress / animal model / mice / knockout / gp91phox / NADPH / 神経科学 / 頭部外傷 / ラット / ESR / gp91

Research Abstract

(Introduction)
The sources of superoxide radical (O2-) production following traumatic brain injury (TBI) are known as some cascades: cyclooxygenase, xanthine oxygenase, NADPH oxygenase. In this study, the kinetics and the roles of gp9lphox(gp91) after traumatic brain injury were investigated using gp9lphox gene knockout mouse.
(Material and Methods)
C57BL mice were used in this study. In the current study, we investigated the time-dependent changes in the expression of the gp9lphox in the mice traumatic brain injury model (TBI) (controlled cortical impact model) using western blotting method. The gp91 positive cells were identified by double immunohistochemical technique. The damaged areas of wild mouse and gp9lphox knockout mouse were also measured on day2 after TBI. Superoxide radical levels were detected by in situ detection of oxidized Het.
(Results)
On day 2 after TBI, the gp91 phox was strongly expressed in microglia mainly. The damaged area was suppressed in gp91 phox knockout mouse. Production of superoxide radical was also suppressed in gp91 phox knockout mouse.
These results indicate that gp91phox and NADPH has the important roles as a generator of free radical in TBI.

Research Products

• [Journal Article] Does edaravone(MCI-186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury? (2007)
  • Author(s): Dohi K, Satoh K, Yofu S, Yoshikawa T, Shioda S, Aruga T.
  • Journal Title: Antioxid Redox Signal 9(2) Pages: 281-287
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Increased mitochondrial DNA oxidative damage after transient middle cerebral artery occlusion in mice (2007)
  • Author(s): Ohtaki H, Dohi K, Yofu S, Nakamachi T, Satoh K, Shioda S.
  • Journal Title: Neurosci Res 58(4) Pages: 349-355
  • NAID: 10024416143
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] CSF hypocretin-1/orexin-A concentrations in patients with intracerebral hemorrhage(ICH) (2007)
  • Author(s): Dohi, K, Aruga, T, Nishino, S, et. al.
  • Journal Title: Regl Pept 145(1-3) Pages: 60-64
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased mitochondrial DNA oxidative damage after transient middle cerebral artery occlusion in mice (2007)
  • Author(s): Ohtaki, H, Takeda, T, Dohi, K, Yofu, S, Nakamachi, T, Satoh, K, Hiraizumi, Y, Miyaoka, H, Matsunaga, M, Shioda, S
  • Journal Title: Neurosci Res 58(4) Pages: 349-55
  • NAID: 10024416143
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Does edaravone(MCI-186)act as an antioxidant and a neuropontector in experimental traumatic brain injury? (2007)
  • Author(s): Dohi, K, Satoh, K, Hiratsuka, K, Nakamura, S, Ohtaki, H, Shioda, S, Yoshikawa, K, Aruga, T
  • Journal Title: Antioxid Redox Signal 9(2) Pages: 281-287
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The surgical procedures of hippocampal ischemia models for the study of regeneration in rats (2007)
  • Author(s): Dohi, K, Ohtaki, H, Kudo, Y, Nakamachi, T, Shioda, S, Aruga, T
  • Journal Title: New Frontiers in Regenerative Medicine. Springer(Tokyo) Pages: 143-152
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Does edaravone (MCI-186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury (2007)
  • Author(s): Dohi K, Satoh K, Yofu S, Ohtaki H, Yoshikawa T, Shioda S, Aruga T.
  • Journal Title: Antioxid Redox Signal Pages: 281-287
  • Peer Reviewed
• [Journal Article] Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury (2007)
  • Author(s): Dohi K, Satoh K, Shioda S, Aruga T, et al.
  • Journal Title: Journal of Neurotrauma 23(11): Pages: 1591-1599
• [Journal Article] Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury (2006)
  • Author(s): Dohi K, Satoh K, Yofu S, Yoshikawa T, Shioda S, Aruga T, et. al.
  • Journal Title: J Neurotrauma 23(11) Pages: 1591-9
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Neuronal damage in rat brain and spinal cord after cardiac arrest and massive hemorrhagic shock (2006)
  • Author(s): Kudo, Y, Ohtaki, H, Dohi, K, et. al.
  • Journal Title: Crit Care Med 34(11) Pages: 2820-2826
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alkoxy radical-scavenging activity of Edaravone(MCI-186) in patients with traumatic brain injury (2006)
  • Author(s): Dohi, K, Nakamura, S, Miyake, Y, Aruga, T, et. al.
  • Journal Title: Joumal of Neurotrauma 23(11) Pages: 1591-1599
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CSF orexin A concentrations and expressions of the orexin-1 receptor in rat hippocampus after cardiac arrest (2006)
  • Author(s): Dohi, K, Nishino, S, Nakamachi, T, Ohtaki, H, Morikawa, K, Takeda, T, Shioda, S, Aruga, T
  • Journal Title: Neuropeptides 40(4) Pages: 245-50
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nasopharyngeal Brain Cooling Method(Positive Selective Brain Cooling Method) (2006)
  • Author(s): Dohi, K., Jimbo, H, Abe, T, Aruga, T., A, Novel, Simple, Selective
  • Journal Title: Acta Neurochir Suppl 96 Pages: 409-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pharmacological Brain Cooling with Indomethacin in Acute Hemorrhagic Stroke (2006)
  • Author(s): Dohi, K, Jimbo, H, Ikeda, Y, Fujita, S, Ohtaki, H, Shioda, S, Abe, T, Aruga, T
  • Journal Title: Acta Neurochir Suppl 96 Pages: 57-60
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Controlled normothermia during ischemia is important for the induction of neuronal cell death after global ischemia in mouse (2006)
  • Author(s): Ohtaki, H, Nakamachi, T, Dohi, K, Yofu, S, Hodoyama, K, Matsunaga, M, Aruga, T, Shioda, S
  • Journal Title: Acta Neurochir Suppl 96 Pages: 249-53
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide(PACAP) decreases ischemic neuronal cell death in association with IL-6 (2006)
  • Author(s): Ohtaki, H, Nakamachi, T, Dohi, K, Aizawa, Y, Shioda, S, et. al.
  • Journal Title: Proc Natl Acad Sci U S A 103(19) Pages: 7488-93
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Free radical monitoring inpatients with severe brain damage (2006)
  • Author(s): Dohi, K, Satoh, K, Nakamura, S, Mihara, Y, Yamamoto, T, Tanaka, K, Miyake, Y, Shioda, S, Aruga, T
  • Journal Title: Neurotraumatology 29 Pages: 20-26
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Does Edaravone (MGI-186) Act as an Antioxidant and a Neuroprotector in Experimental Traumatic Brain Injury? (2006)
  • Author(s): Dohi K, Satoh K, Shioda S, Aruga T, et al.
  • Journal Title: Antioxid Redox Signal 9(2) Pages: 281-287
• [Presentation] gp91 phoxノックアウトマウスを用いたNADPH oxidase依存性活性酸素の頭部外傷における役割 (2007)
  • Author(s): 土肥 謙二, 養父 佐知子, 佐藤 和恵, 中町 智哉, 塩田 清二, 有賀 徹
  • Organizer: 第35回日本救急医学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-17
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] gp91phoxノックアウトマウスを用いたNADPH oxidase依存性活性酸素の頭部外傷における役割 (2007)
  • Author(s): 土肥 謙二, 養父 佐知子, 佐藤 和恵, 中町 智哉, 塩田 清二, 有賀 徹
  • Organizer: 第35回日本救急医学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-17
• [Presentation] Oxidant and antioxidant balances during brain hypothermia therapy in patients with traumatic brain injury (2007)
  • Author(s): Kenji, Dohi, Kazue, Satoh, Shunsuke, Nakamura, Yuko, Mihara, Yasufumi, Miyake, Seiji, Shioda, Tohru, Aruga
  • Organizer: The 2nd International Brain Hypothermia Symposium
  • Place of Presentation: Miami, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Neuroprotective effect of Edaravone in rat traumatic brain injury model- The kinetics of oxidative stress and antioxidant potency (2007)
  • Author(s): Kenji, Dohi, Kazue, Satoh, Sachiko, Yofu, Tomoya, Nakamachi, Shunsuke, Nakamura, Seiji, Shioda, Tohru, Aruga
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism& Function
  • Place of Presentation: Osaka, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The roles of gp91phox in Traumatic brain injury in mice(Best presentation Awards) (2007)
  • Author(s): Kenii, Dohi, Tomoya, Nakamachi, Sachiko, Yofu, Yuko, Mihara, Kentaro, Morikawa, Hirokazu, Ohtaki, Kazue, Satoh, Seiji, Shioda, Tohru, Aruga
  • Organizer: The 35th JAAM
  • Place of Presentation: Osaka, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] The roles of gp9lphox in Traumatic brain injury in mice (2007)
  • Author(s): Kenji, Dohi, Tomoya, Nakamachi, Sachiko, Yofu, Yuko, Mihara, Kentaro, Morikawa, Hirokazu, Ohtaki, Kazue, Satoh, Seiji, Shioda, Tohru, Aruga
  • Organizer: The 113th Japan association of Anatomist
  • Place of Presentation: Osaka, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] A Method of Blood Free radical Monitoring in Brain Injury : An ESR study (2006)
  • Author(s): Kazue, Satoh, Kenji, Dohi, Tohru, Aruga, Hirokazu, Ohtaki, Seiji, Shioda, et. al.
  • Organizer: The 13th Congress of SFRRI
  • Place of Presentation: Davos, Swizerland
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] New Frontiers in Regenerative Medicine(The Surgical Procedures of Hippocampal Ischemia Models for the Study of Regeneration in Rats) (2007)
  • Author(s): Dohi K, Ohtaki H, Kudo Y, Nakamachi T, Shioda S, Aruga T
  • Total Pages: 154
  • Publisher: Springer Japan
  • Description: 「研究成果報告書概要(和文)」より