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虚血における自然免疫機構(Toll様受容体)の関与

Research Project

Project/Area Number 18659421
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

朱 鵬翔  Ehime University, 大学院・医学系研究科, 助教 (40380216)

Co-Investigator(Kenkyū-buntansha) 大西 丘倫  愛媛大学, 大学院・医学系研究科, 教授 (70233210)
久門 良明  愛媛大学, 大学院・医学系研究科, 准教授 (80127894)
秦 龍二  愛媛大学, 大学院・医学系研究科, 准教授 (90258153)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2007: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsTLR4 / Cerebral ischemia / Neuronal cell death / cerebral ischemia / 自然免疫 / 神経細胞死
Research Abstract

自然免疫とは、微生物感染時に迅速に機能する免疫応答機構であり、昆虫から哺乳類まで進化上幅広く存在している。最近外来微生物に共通する分子構造を認識し、細胞内シグナル伝達系を活性化するToll様受容体(TLR)と呼ばれる一連の膜蛋白質の構造と機能が明らかとなってきた(Nat Immunol 2;675-680,2001)。TLR familyのうちTLR4はグラム陰性桿菌の外膜に存在するリポ多糖類(LPS)にと結合し、細胞内シグナル伝達を活性化する事が知られている(Science 282:2085-88,1998)。これ以外にTLR4はネクローシスによる細胞死に伴う炎症性反応(TNF-alpha,IL-1beta,iNOS等の発現)に関与する事が知られている(J Immunol 166;7128-35,2001)。そこで本研究では脳虚血・再灌流障害により引き起こされる炎症反応にTLR4が関与しているかどうかを検討した。その結果、TLR4 knock-out(TLR4KO)マウスとそのwild type(Wt)マウスで脳虚血病変に差があるかどうかを中大脳動脈永久閉塞モデルと一過性閉塞モデルとで検討した。その結果、永久閉塞モデルでも一過性閉塞モデルでもTLR4KOマウスで梗塞量の減少が認められた。次いでWtマウスに致死量の放射線を照射後、TLR4KOマウスの骨髄を移植すると、Wtマウスの骨髄を移植する場合に比して有意に梗塞量の減少が認められた。更に初代培養神経細胞に4時間の低酸素負荷を与えた後、マイクログリアと共培養すると、TLR4KOマウス由来のマイクログリアと共培養した方がWtマウス由来のマイクログリアと共培養した場合より、優位に神経細胞障害が軽減した。従って脳虚血障害機構に骨髄由来の単球・マクロファージが密接に関与すると考えられた。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (12 results)

All 2007 2006

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (8 results)

  • [Journal Article] Intravenous Infusion of Dihydroginsenoside Rb1 Prevents Compressive Spinal Cord Injury and Ischemic Brain Damage through Upregulation of VEGF and Bcl-xL2007

    • Author(s)
      Sakanaka M, Zhu P, Zhang Bo, Wen TC, Cao F, Ma YJ, Samukawa K, Mitsuda N, Tanaka J, Kuramoto M, Uno H, Hata R.
    • Journal Title

      Journal of Neurotrauma 24

      Pages: 1037-1054

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida T, Hakuba N, Morizane I, Fujita K, Cao F, Zhu P, Uchida N, Kameda K, Sakanaka M, Gyo K, Hata R
    • Journal Title

      Neuroscience 145

      Pages: 923-930

    • Related Report
      2007 Annual Research Report 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression.2006

    • Author(s)
      Zhang B, Hata R, Zhu P, Sato K, Wen TC, Yang L, Fujita H, Mitsuda N, Tanaka J, Samukawa K, Maeda N, Sakanaka M
    • Journal Title

      J Cereb Blood Flow Metab 26

      Pages: 708-721

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells.2006

    • Author(s)
      Cao F, Hata R, Zhu P, Ma YJ, Tanaka J, Hanakawa Y, Hashimoto K, Niinobe M, Yoshikawa K, Sakanaka M
    • Journal Title

      J Neurochem. 98

      Pages: 459-470

    • Related Report
      2006 Annual Research Report
  • [Presentation] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects2007

    • Author(s)
      Yoshida T, Hata R, Hakuba N, Cao F, Zhu P, Sakanaka M, Gyo K.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Protective effects of dihydrogeninsenoside Rb1 on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL2007

    • Author(s)
      Hata R, Cao F, Zhu P, Samukawa K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Overexpression of Stat3 promotes neuronal cell death through activation of microglia2007

    • Author(s)
      Hata R, Cao F, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Microglia promotes astrogliogenesis of the neural stem cells through activating Jak/Stat signaling2007

    • Author(s)
      Zhu P, Hata R, Cao F, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Upregulation of syntaxinl in the ischemic cortex fblowing permanent focal ischemia in rats2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Targeted disruption of organic cation transporter 3 in mice reducesischemic brain injury through down-regulation of IL-6 and MCP-12007

    • Author(s)
      Zhu P, Hata R, Ogasawara M, Cao F, Maeyama K, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Delayed neuronal cell death in the brain stem after transient ischemia in gerbils2007

    • Author(s)
      Cao F, Hata R, Zhu P, Sakanaka M.
    • Organizer
      The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] α-synuclein promotes neuronal cell death through the activation of microglia2007

    • Author(s)
      Hata R, Zhu P, Cao F, Sakanaka M, Tanabe H.
    • Organizer
      International Psychogeriatric Association 25th Anniversary Meeting
    • Place of Presentation
      Osaka,Japan
    • Related Report
      2007 Annual Research Report

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

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