2004 Fiscal Year Final Research Report Summary
Mechanisms of behavioral disorders following neonatal Hypoxic Ischemic-Encephalopathy and effect of treatment with Caspase inhibitor
| Project/Area Number |
15591156
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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 |
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Principal Investigator |
TAKADA Satoshi Kobe University, School of Medicine, Faculty of Health Science, Professor, 医学部保健学科, 教授 (10216658)
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| Co-Investigator(Kenkyū-buntansha) |
TSUNEISHI Shuichi Kobe University, Graduate School of Medicine, Department of Pediatrics, Associate Professor, 医学部附属病院, 助教授 (10271040)
KITAYAMA Shinji Kobe University, Graduate School of Medicine, Department of Pediatrics, Assistant Professor, 大学院・医学系研究科, 助手 (10346257)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Hypoxic-ischemic encephalopathy / Neonatal rat / Caspase / Caspase Inhibitor / Moris water maze / Behavioral disorder |
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| Research Abstract |
PURPOSES
Caspases play a key role in the delayed neuronal cell death observed in the rat brain following hypoxic-ischemic (HI) insult. Hippocampal damage after HI insult is strongly related to learning memory. In this study, we examined the influences of neonatal HI on learning ability by using the Morris's water maze, and on physical ability by the Rota rod test. Furthermore, we examined the protective effect of the treatment with caspase inhibitor.
METHODS
Postnatal day 7 rat pups were subjected to the Rice model of hypoxia for 2.5h. (HIE group, n:15). Sham-operation was completed in the control rats without HI loading (n:15). For the treatment groups, two different administration schedules were prepared. Just before HI insult, a pan-caspase inhibitor, boc-aspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the BAF 1 group (n:15), and the same dose of BAF was added 12hrs after HI loading in the BAF 2 group (n:5) Caspase 3 activitiy of the hippocampus was measured in each group at 24 hrs after HI loading. Learning and physical abilities were assessed at the age of 35 days.
RESULTS
1.Although there was no significant difference in the physical ability among the four groups, learning ability was significantly decreased in the HIE groups in comparison with the control group. The effect of the treatment with BAF could not be observed in either treatment group.
2.The Caspase 3 activities were remained in low value in the control rats, and there was not any difference between the right and left Hippocampus. In the HIE group(without the treatment), the level of Caspase 3 was distinctly elevated in the left side (right side:0.85± 0.06 unit/mg protein/mm, left side: 6.4±1.7 unit/mg protein/mm. The elevation of Caspase 3 activities in the injured side was inhibited by the treatment with BAF.
CONCLUSION
The treatment with BAF inhibited the elevation of Caspase 3 activity in the injured Hippocampus, but it failed to improve the cognitional dysfunction following neonatal HIE.
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Research Products
(8 results)
