Neuroprotective effects of inhalation anesthetics based on the analysis of the signal transduction related to ubiquitous protein kinases.
| Project/Area Number |
15591659
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
MATSUMOTO Shohei Tokyo Medlical University, Medicine, lecturer, 医学部, 講師 (30256250)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| 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)
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| Keywords | cerebral 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 |
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| 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.
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Report
(3 results)
Research Products
(10 results)
