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Neuroprotective effects of inhalation anesthetics based on the analysis of the signal transduction related to ubiquitous protein kinases.

Research Project

Project/Area Number 15591659
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionTokyo Medical University

Principal Investigator

MATSUMOTO Shohei  Tokyo Medlical University, Medicine, lecturer, 医学部, 講師 (30256250)

Co-Investigator(Kenkyū-buntansha) MUROZONO Michihiro  Tokyo Medical University, Medicine, lecturer, 医学部, 講師 (70276947)
ISSIKI Atsushi  Tokyo Medical University, Medicine, professor, 医学部, 教授 (60074796)
WATANABE Yasuo  Tokyo Medical University, Medicine, associate professor, 医学部, 助教授 (70183720)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordscerebral ischemia / Isoflurane / Sevoflurane / Midazoram / Propofol / PKC-_Y / CaMKII-_α / phospho-CaMKII / 吸入麻酔薬 / PKCγ / CaMkIIα / トランスロケーション
Research Abstract

We aimed to clarify the neuroprotective mechanism of Isoflurane and Sevoflurane using mice decapitation model. C57/black mice were exposed 1.5 MAC Isoflurane or Sevoflurane and decapitated after checking their loss of right reflex, and they were frozen and stored. The brains were homogenized and centrifuged into the elude P2 (synaptosomal ), P3 ( particulate ), and S3 ( cytosolic ) fractions. SDS-PAGE was performed with each sample and CaMKII-_α, PKC-_Y, phospho-CaMKII, and phospho-tyrosine levels were analyzed by immnoblotting. The significant inhibition of CaMKII-_α translocation to P2 from S3 were seen in the Isoflurane and Sevoflurane inhalation groups. In addition, Isoflurane inhibites the CaMKII translocation more significantly compared to that of Sevoflurane. These results suggest that Isoflurane and Sevoflurane have the neuroprotective effects due to the inhibition of CaMKII signalling cascade.
On the other hand, we found that in the ischemic mice brain, phospho-CaMKII does not exists in the cytosol, nothing but in the synaptic membranes. This result indicates that the inhibition of CaMKII phosphorylation may contribute for the neuroprotective action of Isoflurane and Sevoflurane.
Intravenous anesthetics Midazoram and Propofol were also investigated same as inhalation anesthetics. No significant change was seen on the PKC nor CaMKII translocation in the ischeunic mice brain administrated 10 mg/kg Midazoram or Propofol. Although these intravenous anesthetics supposed to have the neuroprotective action, PKC or CaMKII signaling cascade may not contribute their actions.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (10 results)

All 2005 2004 Other

All Journal Article (8 results) Publications (2 results)

  • [Journal Article] 新規PACAP誘導体のグリア細胞を介する脳保護効果2005

    • Author(s)
      宮本麻央 室園美智博, 松本晶平, 一色淳, 渡辺泰雄
    • Journal Title

      蘇生 24(1)

      Pages: 10-16

    • NAID

      10015565547

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neuroprotective effects of a novel PACAP derivative depending on presence Of glia cells2005

    • Author(s)
      Miyamoto M., Murozono M,.Matsumoto S., Isshiki A., Watanabe Y.
    • Journal Title

      Sosei 24(1)

      Pages: 10-16

    • NAID

      10015565547

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 新規PACAP誘導体のグリア細胞を介する脳保護効果2005

    • Author(s)
      宮本麻央, 室園美智博, 松本晶平, 一色淳, 渡辺泰雄
    • Journal Title

      蘇生 24(1)

      Pages: 10-16

    • NAID

      10015565547

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibitory effects of extracellular matrix modulators on lipopolysaccharide (LPS) and acidosis-damaged glia containing cerebellar granule cell cultures2004

    • Author(s)
      Fukui H., Fukui Y., Noguchi M., Kameyama Y., Isshiki A., Watanabe Y.
    • Journal Title

      Neurochemical Research 29(4)

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdrla knockout mice.2004

    • Author(s)
      Murozono M., Matsumoto S., Matsumoto E., Isshiki A., Watanabe Y.
    • Journal Title

      European Journal of Pharmacology 498

      Pages: 115-118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdrla knockout mice2004

    • Author(s)
      Murozono M., Matsumoto E., Isshiki A., Watanabe Y.
    • Journal Title

      European Journal of Phamacology 408

      Pages: 115-118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory effects of extracellular matrix modulators on lipopolysaccharide (LPS) and acidosis-damaged gila containing cerebellar granule cell cultures2004

    • Author(s)
      Fukui H., Fukui Y., Noguchi M., Kameyama Y., Isshiki A., Watanabe Y.
    • Journal Title

      Neurochemical Research 29(4)

      Pages: 53-57

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdr1a knockout mice2004

    • Author(s)
      Murozono M., Matsumoto S., Matsumoto E., Isshiki A., Watanabe Y.
    • Journal Title

      European Journal of Pharmacology 498

      Pages: 115-118

    • Related Report
      2004 Annual Research Report
  • [Publications] 松本恵理子, 松本晶平, 室園美智博, 渡辺泰雄, 一色淳: "イソフルレンがマウス脳虚血時のプロテインキナーゼCとカルシウムカルモヂュリン依存性プロテインキナーゼIIのトランスロケーションに与える影響"蘇生. 23(1). 1-7 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shohei Matsumoto, Mehrdad Shamloo, Eriko Matsumoto et al.: "Protein kinase C-γ and Calcium/Calmodulin-dependent protein kinase II-α are persistently translocated to cell membranes of the rat brain during and after midd"Journal of Cerebral Blood Flow and Metabolism. 24. 54-61 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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