| Project/Area Number |
15591155
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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 |
TSUNEISHI Syuichi Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (10271040)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Naoki Kobe University, Hospital, Lecturer, 医学部附属病院, 講師 (20314487)
大橋 玉基 神戸大学, 医学部附属病院, 講師 (60362779)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | apoptosis / hypoxic-ischemic encephalopathy / caspase / platelet-derived growth factor / BAF / myelin / PDGF-α receotor / BAF / Morris水迷路 / トロンビン受容体 / PAR-1 / 血小板由来成長因子 |
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| Research Abstract |
The aim of this study is to produce a new strategy to prevent neonatal brain damage against hypoxic-ischmic insult through regulating glial differentiation and apotosis.
We determined that the expression of PDGF-α receptor mRNA and protein increased in the damaged cerebral region of the neonatal rat HIE model. Activation of PDGF-α receptor results in inhibition of differentiation of pre-oligodendorglia, which is the main component to form myelin sheath. Both MBP and PLP proteins, myelin forming proteins, did appear in the damaged region earlier than non-damaged region. This phenomenon is considered as hyper-myelination. PDGF-α receptor is one of the modulator in differentiation of glial cells so that regulating its activation opens a strategy to prevent neonatal brain damage.
Next issue is to evaluate the efficacy of caspase inhibitor to protect the higher function of cerebrum, especially spatial memory. Intra-ventricular injection of BAF, a pan-caspase inhibitor, decreased the activity of caspase-3 in the damaged side of hippocampal tissue at 24h after HIE insult. However, at 4 weeks after HIE insult Morris water maze test failed to show the leaming capacity in the treated group. Though BAF administration may succeed in inhibiting apoptotic cell death, necrotic cell death and disorder in forming neuronal networks may result in deterioration of higher brain function.
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