1994 Fiscal Year Final Research Report Summary
Treatment of Neurodegenerative disease with recombinent cells
| Project/Area Number |
04557064
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | National Cardio Vascular Center Research Institute |
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Principal Investigator |
TSUKAHARA Tetsuya Dept.Etiology and Pathogenesis, Staff, 病因部, 室員 (30217278)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Takashi Kyoto Pharmaceutical University, Professor, 薬学部, 教授 (10111957)
SHIMOHARA Shun Kyoto University, assistant professor, 医学部, 助手 (60235687)
TANIGUCHI Takashi Kyoto Pharmaceutical University, Professor
TANIGUCHI Takashi Kyoto Pharmaceutical University, Professor
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| Project Period (FY) |
1992 – 1994
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| Keywords | Recombinant brain-derived neurotrophic factor / Nerve growth factor / Neurotoxicity / Neurodegenerative disease / Parkinson's disease / Cerebral ischemia |
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| Research Abstract |
1) The effect of recombinant brain-derived neurotrophic factor (BDNF) nerve growth factor (NGF) on cultured rat cortical neurons was examined. Brief exposure of cortical neurons to glutamate followed by incubation with glutamate-free medium reduced cell viability by 60-70% when compared with the control value. Simultaneous addition of recombinant BDNF NGF to rat cortical cultures with glutamate did not effect this reduction of cell viability. However, 24h pretreatment of rat cortical cultures with recombinant BDNF NGF resulted in a significant reduction of glutamate-induced neuronal damage. These findings suggest that BDNF NGF can protect cortical neurons against glutamate-induced neurotoxicity.
2) We investigated alterations in BDNF and NGF gene expression and the effect of BDNF and NGF on neuronal death after transient forebrain ischemia in the rat brain. The results suggested that BDNF and NGF gene expression was enhanced by transient ischemia both in the hippocampus and the cerebral
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cortex and that BDNF or NGF,at a sufficient dose, has a preventive effect on the delayd hippocampal neuronal death observed after transient forebrain ischemia.
3) The effects of the intrathecal infusion of brain-derived neurotrophic factor (BDNF) were examined in a l-methy1-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP) -induced parkinsonian model in monkeys. The BDNF-treated animals remained asymptomatic during the first week and showed mild parkinsonism during the second week, whereas the non-BDNF group showed typical parkinsonian syndrome during the first week, deteriorating in the second week. Histological damage in the substantia nigra correlated well with the clinical features. Severe neuronal cell loss in the substantia nigra was observed in animals with severe Parkinsonism (those in the non-BDNF group), while the neuronal cell damage in the substantia nigra was significantly less in the BDNF group. These findings suggest that BDNF has may have a preventive effect on the neurological syndrome and the histological damage of the substantia nigra in MPTP-induced Parkinsonism in monkeys. Less
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