| Project/Area Number |
10557128
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
SAKANAKA Masahiro Ehime University, School of Medicine, Professor, 医学部, 教授 (60170601)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Junya Ehime University, School of Medicine, Professor, 医学部, 教授 (70217040)
SATO Kohji Hamamatsu University, School of Medicine, Professor, 教授 (80235340)
MAEDA Nobuji Ehime University, School of Medicine, Professor, 医学部, 教授 (50036464)
WEN Tong-chun Ehime University, School of Medicine, Research assistant, 医学部, 助手 (70284411)
DESAKI Junzo Ehime University, School of Medicine, Lecturer, 医学部, 講師 (00036451)
榊 三郎 愛媛大学, 医学部, 教授 (30116933)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2000: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Prostaglandin I2 analog / Brain ischemia / Passive avoidance task / Delayed neuronal death / Apoptosis / Bax / アラマーブルー / 一酸化窒素 / Bax / RT-PCR / ウエスタンブロット / 一過性前脳虚血 / 海馬 / 脳卒中易発症高血圧自然発症ラット / 中大脳動脈皮質枝永久閉塞 / 場所学習障害 / 脳梗塞 |
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| Research Abstract |
The 7-day infusion of a prostaglandin I2 analog TEI-7165 into the lateral ventricle of gerbils starting 2 hours before or just after 3-min forebrain ischemia is known to prevent the occurrence of learning disability and neuronal death in the hippocampal CA1 field. However, it remains to be determined whether or not intracerebroventricular infusion of TEI-7165 starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which TEI-7165 exerts a protective effect on ischemic hippocampal CA1 neurons also remains to be determined. In the first set of the present experiments, gerbils were infused with TEI-7165 for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. TEI-7165 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. In the second set of the present experiments, TEI-7165 prevented in vitro neuronal apoptosis or apoptotic neuron death caused by the nitric oxide (NO) donor sodium nitroprusside (SNP) in a concentration-dependent manner. Moreover, TEI-7165 (10^<-3>〜10^<-1> fg/ml) inhibited the expression of Bax, a proapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates a potent neuroprotective effect of TEI-7165 on ischemic hippocampal neurons in vivo possibly through inhibition of the expression of the proapoptotic factor, Bax.
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