| Project/Area Number |
05404032
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
YANAGIHARA Takehiko Osaka Univ., Dept.of Neurology, Professor, 医学部, 教授 (70243201)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Hirokazu Osaka University Hospital, Dep.t of Neurology, Clinical Fellow, 医学部・付属病院, 医員
NAKAMURA Masaichi Osaka Univ., Dept.of Neurology, Assistant Professor, 医学部, 助手 (50243225)
MATSUMOTO Masayasu Osaka Univ., Dept.of Neurology, Assistant Professor, 医学部, 助手 (20192346)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1994: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1993: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Cerebral Ischemia / Magnetic Resonance Imaging / Diffusion / Immunohistochemistry / Energy Metabolism / Microtubule-Associated Proteins / Selective Vulnerability / Cytotoic Edema / Diffusin |
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| Research Abstract |
To elucidate the pathophysiological mechanism for ischemic irreversible damage, we analyzed the sequential changes of biochemical and physiological parameters by use of HPLC,near infra-red spectro-photometry and magnetic resonance imaging, and compared them with the immunohistochemical changes in the gerbil model of cerebral ischemia.
1. We established the method for the simultaneous assessment of changes in regional levels of energy metabolites and immunohistochemical changes in brain tissues of 10 to 50 microgram dry weight. The decrease of regional ATP level seemed prerequisite for the development of immunohistochemical damages.
2. The diffusion-weighted magnetic resonance imaging showed prompt decrease of diffusion coefficient of tissue water, indicating ion pump failure as the results of energy failure caused cytoskeletal and cell damage.
3. The results by near-infrared spectroscopy indicated complete reduction of cytochrome oxidase seemed preceded for the decrease of ATP.
4. The comparison of vulnerability between tubulin and MAPIA indicated damages of tubulin seemed more closely related to irreversible damage than those of MAPIA in ischemia.
5. The regional decrease in N-acetyl aspartate levels was detected in the area of delayd neuronal death, indicating the sensitive marker for the neuronal loss and irreversible damages in the brain.
6. In hypoxia/reoxygenation model using cultured astrocytes, similar derangement of energy states and induction of stress proteins were observed as in the gerbil model of cerebral ischemia.
7. In hindbrain regions, selective vulnerability to the ischemia existed as in the case of forebrain ischemia. From these results, irreversible damages in cerebral ischemia could be the result of complete reduction of cytochrome oxidase, ATP depletion, ion pump failure, and degradation of cytoskeletal proteins.
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