| Project/Area Number |
11671370
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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 |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
DESAKI Junzo Ehime University, School of Medicine, Assistant Professor, 医学部, 講師 (00036451)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Kohji Hamamatsu University, School of Medicine, Professor, 教授 (80235340)
TANAKA Junya Ehime University, School of Medicine, Professor, 医学部, 教授 (70217040)
SAKANAKA Masahiro Ehime University, School of Medicine, Professor, 医学部, 教授 (60170601)
WEN Tong-chun Ehime University, School of Medicine, Instructor, 医学部, 助手 (70284411)
榊 三郎 愛媛大学, 医学部, 教授 (30116933)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | secondary neuronal degeneration / gerbil / hippocampus / prosaposin-related peptide / apoptosis / Bcl-x_L / passive avoidance experiment / 神経細胞の二次変性 / 一過性前脳虚血 / インターロイキン3 / エリスロポエチン / ジンセノサイドRb_1 |
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| Research Abstract |
The 7-day infusion of a prosaposin-related 18-mer peptide (18-MP) 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 the 18-MP starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which the 18-MP 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 the 18-MP for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. 18-MP 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 the 18-MP than in those receiving vehicle infusion. In the second set of the present experiments, the 18-MP 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, the 18-MP (1-10^5 fg/ml) increased the expression of Bcl-x_L, an antiapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates that the 18-MP prevents secondary neuronal degeneration after ischemia in vivo possibly through an increase in the expression of the antiapoptotic factor, Bcl-x_L.
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