Basic analysis for the role of Na+/Ca2+ exchanger on ischemic brain damage to establish new brain resusciataion method
| Project/Area Number |
18591724
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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 |
UTINO Hiroyuki Tokyo Medical University, School of Medicine, Assistant Professor (60266476)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBAZAKI Hutoshi Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Senior Researcher (90300954)
IWAMOTO Takahiro Fukuoka University, Faculty of Medicine, Professor (20300973)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Brain ischemia / Na+ / Ca2+ exchanger / mitochondria / Respiratory Control Ratio / Hippocampal Slice / Calcineurin / immunophilin / CyclosporinA / NA+ / 細胞内Ca2+ / 脳障害 |
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| Research Abstract |
To investigate the mechanisms of ischemic neuronal cell death, we explored the planned experiments to focus on the relationship between the function of astrocytic Na+/Ca2+ exchanger and intracerebral Ca2+ dynamics, calcineurin/immunophilin cascade, and mitochondrial dysfunction based on Mitochondrial Permeability Transition(MPT) and also investigated the role of Na+/Ca2+ exchanger for the formation of ischemic neuronal cell death. We have used Na+/Ca2+ exchanger KO mouse(NCXKO) for our experiments.
From our pathohistological analysis, NCXKO group did not show any protective effect in mice forebrain ischemia model. NCXKO mice hippocampal slice experiments showed the high intracellular Ca2+ level but not mitochondrial compared to wild group, however, Cyclosporin A also inhibited both the rise of intracellular and intramitochondrial Ca2+ as same as wild group. NCXKO group and wild group showed no significant difference in terms of mitochondrial swelling and calcium retension capacity(CRC) due to Ca2+ overlaod.Respiratory control ratio(RCR) in NCXKO mice showed high oxygen consumption at state 3. From our results, we could speculate the reason why we could not get neuroprotectio is that mice was not homozygous, so gene deletion was not enough to explore the neuroprotection. But from the results of hippocampal slice experiments, we considered that NCX is somehow deleted. Mitochondrial permeability transition was induced in both NCXKO and wild mice and these results suggested that NCX gene deletion does not affect the inhibition of mitochondrial dysfunction. We have speculated the reseason why oxygen consumption was high in NCXKO mice is that Ca2+ extrusion to extracellular space in NCXKO mice need long time compared to wild one, so mitochondria need to produce ATP consuming huge amount of oxygen. From our results, importance of Na+/Ca2+ exchanger was explored.
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Report
(3 results)
Research Products
(55 results)
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[Journal Article] Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent differences in sensitivity to cyclophilin D inhibition2007
Author(s)
Morota, S, Hansson, MJ, Ishii, N, Kudo, Y, Elmer, E, Uchino, H
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Journal Title
J Neurochem 103(5)
Pages: 2066-76
Description
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[Journal Article] Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline2007
Author(s)
Mansson, R, Hansson, MJ, Morota, S, Uchino, H, Ekdahl, CT, Elmer, E
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Journal Title
Neurobiol Dis 25(1)
Pages: 198-205
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[Journal Article] 脳障害のメカニズム2006
Author(s)
内野 博之, 諸田 沙織, Chen Li, 高橋 俊明, 工藤 佳久, 石井 脩夫, 芝崎 太
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NAID
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[Journal Article] 虚血性神経細胞死のメカニズム2006
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内野 博之, 諸田 沙織, 牛島 一男, Chen Li, 高橋 俊明, 池田 幸穂, 工藤 佳久, 石井 脩夫, 芝崎 太
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[Journal Article] 蘇生後脳症における脳循環代謝2006
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黒田 泰弘, 山下 進, 中村 丈洋, 河北 賢哉, 西由 佳宏, 河井 信行, 内野 博之
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Journal Title
日救急医会誌(JJAAM) 17
Pages: 167-176
NAID
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[Journal Article] A Novel Neuroprotective Compound FR901459 with Dual Inhibition of Calcineurin and Cyclophilins2006
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Uchino, H, Morota, S, Takahashi, T, Chen, Li, Ikeda, Y, Kudo, Y, Ishii, N, Siesjo, BK, Shibasaki, F
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Journal Title
Acta Neurochir Sppl
Pages: 157-162
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[Journal Article] Search the Novel Genemakers for Traumatic Brain Injury by Time Differential Microarray Analysis2006
Author(s)
Yu-ichiro, Ishikawa, Hiroyuki, Uchino, Saori, Morota, Chen, Li, Toshiaki, Takahashi, Yukio, Ikeda, Nagao, Ishii, Futoshi, Shibasaki
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Journal Title
Acta Neurochir Sppl
Pages: 163-167
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[Presentation] 脳低温療法中の尿中フリーラジカルについて2007
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池田 一美, 池田 寿昭, 上野 琢哉, 横山 智仁, 須田 慎吾, 内野 博之
Organizer
第21回日本神経救急学会
Place of Presentation
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Year and Date
2007-06-16
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Author(s)
内野 博之
Organizer
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Year and Date
2007-01-12
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[Presentation] Molecular mechanisms of cerebral nerve injuries during intensive care and possible drug-mediated protection of brain2006
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Organizer
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Place of Presentation
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Year and Date
2006-04-16
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