Treatment of Neurodegenerative disease with recombinent cells

用重组细胞治疗神经退行性疾病

• 批准号: 04557064
• 负责人: TSUKAHARA Tetsuya
• 金额: $ 6.34万
• 依托单位: National Cardio Vascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557064/
• 关键词: Recombinant brain-derived neurotrophic factor; Nerve growth factor; Neurotoxicity; Neurodegenerative disease; Parkinson's disease; Cerebral ischemia; Brain derived neurotrophic factor; 脳虚血; 神経変性疾患

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 … More 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

1)观察了重组脑源性神经营养因子（BDNF）和神经生长因子（NGF）对体外培养的大鼠皮层神经元的作用。与对照值相比，皮质神经元短暂暴露于谷氨酸，随后与无谷氨酸培养基孵育，细胞活力降低60-70%。同时添加重组BDNF-神经生长因子与谷氨酸的大鼠皮层培养细胞活力的减少没有影响。然而，24小时预处理的大鼠皮质培养物与重组BDNF神经生长因子导致谷氨酸诱导的神经元损伤显着减少。这些结果表明，BDNF和NGF可以保护皮层神经元免受谷氨酸诱导的神经毒性。2）我们研究了BDNF和NGF基因表达的变化和BDNF和NGF对短暂性前脑缺血后神经元死亡的影响。结果提示，短暂性脑缺血后海马和脑组织BDNF和NGF基因表达增强 ...更多信息 脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）可抑制短暂性前脑缺血后海马神经元的迟发性死亡。3）在1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1，2，3，6-tetrahydropiridine，MPTP）诱导的猴帕金森病模型中，观察鞘内注射BDNF的作用。BDNF治疗的动物在第一周内保持无症状，在第二周内表现出轻度帕金森综合征，而非BDNF组在第一周内表现出典型的帕金森综合征，在第二周恶化。黑质的组织学损害与临床特征相关。在患有严重帕金森症的动物（非BDNF组）中观察到黑质中严重的神经元细胞损失，而BDNF组中黑质中的神经元细胞损伤显著较少。提示BDNF可能对MPTP诱发的帕金森病猴神经系统综合征和黑质组织学损害具有预防作用。少

项目成果

K.Tanaka,T.Tsukahara et al.: "Effect of nerve growth factor on delayed neuronal death and micro tubule-associated protein 2 after transient cerebral ischemia the rat." J.Clinical Neuroscience. 1. 125-130 (1994)

K.Tanaka、T.Tsukahara 等人：“神经生长因子对大鼠短暂性脑缺血后延迟性神经元死亡和微管相关蛋白 2 的影响。”

Yasuhiko Kaku: "Alterations of 200KDa neurofilament in the rat hippocampus after torebrain ischemia" Journal of Cerebral Blood Flow and Metabolism. 13. 402-408 (1993)

Yasuhiko Kaku：“脑缺血后大鼠海马中 200KDa 神经丝的改变”《脑血流与代谢杂志》。

Tetsuya Tsukahara: "Brain-derived neurotrophic factor after transient forebrain ischemia in the rat hippocampus" Journal of Cerebral Blood Flow and Metabolism(suppl 1). 13. S57 (1993)

Tetsuya Tsukahara：“大鼠海马短暂前脑缺血后的脑源性神经营养因子”《脑血流与代谢杂志》（增补1）。

Shun Shimohama: "Protective effect of recombinant human nerve growth factor against glatmate-induced neurotocity in the cultured cortical neurons" Brain Research. 632. 296-302 (1993)

Shun Shimohama：“重组人神经生长因子对培养的皮质神经元中谷氨酸诱导的神经致动性的保护作用”大脑研究。

Y.Kaku,Y.Yonekawa,T.Tsukahara,N.Ogata,T.Kimur,T.Taniguchi,: "Alterations of a 200KDa neurofilament in the rat hippocampus after forebrain ischemia" Journal of Cerebral Blood Flow and Metabolism in press(1993年).

Y. Kaku、Y. Yonekawa、T. Tsukahara、N. Ogata、T. Kimur、T. Taniguchi，：“前脑缺血后大鼠海马中 200KDa 神经丝的改变”《脑血流与代谢杂志》出版（1993 年）年）。