Effects of Caspase Inhibitor Administration against Hypoxic-Ischemic Brain Damage in Neonatal Rats.
| Project/Area Number |
11671069
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Kobe University. School of Medicine, Faculty of Health Science |
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Principal Investigator |
TAKADA Satoshi Kobe University. School of Medicine, Faculty of Health Science, Professor, 医学部, 教授 (10216658)
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| Co-Investigator(Kenkyū-buntansha) |
SHUICHI Tsuneishi Kobe University. School of Medicine, Department of Pediatrics, Assistant Professor, 医学部・附属病院, 助手 (10271040)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Caspase Inhibitor / Hypoxic-ischemic encephalopathy / Neonatal rat / Hypothermia / Apoptotic cell death / 新生児 / 低酸素性虚血性脳症 / 低体温療法 / caspase / apoptosis / caspase inhibitor(BAF) |
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| Research Abstract |
Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain following hypoxic-ischemic (HI) insult. Caspase inhibitors have been developed as anti-apoptotic agents. Hippocampal damage after HI insult is strongly related to tissue temperature, and systemic hypothermia has been introduced clinically for brain protection. In this study, we examined the effects of a caspase inhibitor and systemic hypothermia on neuronal protection in the developing rat brain. Postnatal day 7 rat pups were subjected to the Rice model of hypoxia for 1 h. Systemic hypothermia was induced with a water bath at 29℃. Prior to HI insult, a pan-caspase inhibitor, boc-aspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the cerebral ventricle. The ipsilateral hippocampus was subjected to caspase assays and histologic assessment. The HI group at 37℃ (HI-37℃) showed a peak of caspase-3 activity 16 h after insult. This activity was significantly reduced in the presence of BAF or hypothermia (HI-29℃ group. p<0.05) or by the combination of HI-29℃+BAF (p<0.01 versus HI-37℃). The number of neuronal cells in the ipsilateral hippocampal CA1 region in the HI-37℃ group was significantly decreased (62.9% versus control). The number of neuronal cells was maintained in the HI-37℃ + BAF group (82.7%), the HI-29℃ group (78.7%), and the combination group (95.2%) (p<0.05 versus HI-37℃). A combination of systemic hypothermia and BAF produced a strong protective effect against neuronal damage in the developing rat brain, along with a reduction in caspase-3 activity.
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Report
(3 results)
Research Products
(6 results)
