| Project/Area Number |
10308034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Osaka University |
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Principal Investigator |
TOHYAMA Masaya Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 教授 (40028593)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Satoshi Kanazawa University School of Medicine, Professor, 医学部, 教授 (90283746)
YAMASHITA Toshihide Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10301269)
玉谷 実智夫 (玉谷 美智夫) 大阪大学, 医学系研究科, 助教授 (30294052)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥36,610,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥810,000)
Fiscal Year 2001: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥23,400,000 (Direct Cost: ¥23,400,000)
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| Keywords | ORP150 / Neuronal cell death / Ischemia / hypoxia / 低酸素負荷 / 細胞死 / アストロサイト / 脳虚血 |
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| Research Abstract |
To study a putative paracellular protective mechanism of astrosytes for neurons, immunohistochemical analysis was performed in ischemic rat brain, which colocalized with the expression of heme oxygase1 (HO-1) in astrocytes surrounding dying, TUNEL positive neurons. As an in vitro paradigm for ischemia, cultured astrocytes were exposed to normobaric hypoxia(pO2〜10 torr), which triggered〜120-fold increase in the expression of a 33 kDa stress protein, identiried as HO-1. Induction of H0-1 message was observed within 4 hrs of hypoxia and peaked at 12 hours, accompanied by an accelerated transcription of HO-1 message. Consistent with the induction of HO-1 a platelet bioassay revealed production of carbon monoxide by reoxygenated astrocytes. The presence of CO in the medium decelerated the hypoxiamediated apoptotic type of cell death in cultreud cerebellar neurons via lowering the activity of CPP32, a key enzyme regulating apoptotic cell death. This protection against apoptosis was likely mediated by CO-mediated increases in intracellular cGMP levels, and addition of cGMP analogue to hypoxic neuronal cultures suppressed CPP32 activity and promoted neuronal survival. These data describe a potentially important paracellular pathway through which astrocytes may rescue neaby neurons from ischemic death.
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