Purification of ischemia induced neurotrophic factor and its application to the vascular dementia

缺血诱导神经营养因子的纯化及其在血管性痴呆中的应用

• 批准号: 02670628
• 负责人: HAYAKAWA Toru
• 金额: $ 1.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670628/
• 关键词: cerebral Ischemia; Neurotrophic Factor; Retrograde Degeneration; bFGF; BFGF Receptor; Thalamic Degeneration

We have detected neurotrophic activity in the brain tissue adjacent to the infarction caused by occlusion of the rat middle cerebral artery. The activity was purified by gel filtration from the samples obtained from cortex and thalamus 12 days after ischemia. The neurotrophic activity was only detected in the periinfarcted cortex and the factor supported both cortical and thalamic neurons. The activity was detected in fractions'with molecular weights of 67k, 32k, 12.4k, and the activity was partly blocked by anti-bFGF antibody. Therefore, we injected recombinant BFGF to the cisterna magna of the rats with middle cerebral occlusion, and BFGF significantly prevented thalamic degeneration after cortical infarction. We then detected expression of BFGF and its receptor MRNA expression. The BFGF MRNA was expressed in neurons and astrocytes 3 days after ischemia but not detected one day after ischemia. Receptor of the BFGF however, detected one day after ischemia and it lasted 7 to 14 days after ischemia. The thalamic neurons, which goes to degeneration had no expression of BFGF or its receptors. The result suggest that cessation of BFGF supply to the thalamic neurons are most likely related to the retrograde degeneration of the thalamus after cortical infarction. Administration of BFGF therefore, prevented degeneration of the thalamic neurons.

我们检测了大鼠大脑中动脉闭塞引起的梗死附近脑组织中的神经营养活性。通过凝胶过滤从缺血后12天从皮层和丘脑获得的样品中纯化活性。神经营养活性仅在梗死周围皮质中检测到，并且该因子支持皮质和丘脑神经元。在分子量为67 k、32 k、12.4k的组分中检测到活性，抗bFGF抗体可部分阻断活性。因此，我们将重组BFGF注射到大脑中动脉闭塞大鼠的枕大池中，BFGF显着阻止皮质梗死后的丘脑变性。然后检测bFGF及其受体mRNA的表达。脑缺血后3d，BFGFmRNA在神经元和星形胶质细胞中有表达，而在脑缺血后1d，BFGFmRNA在神经元和星形胶质细胞中无表达。而bFGF受体在缺血后1天即有表达，并持续7 ~ 14天。丘脑神经元中bFGF及其受体均不表达，并趋于退变。结果提示，皮质梗死后丘脑神经元bFGF供应的停止很可能与丘脑的退行性变性有关。因此，施用BFGF防止了丘脑神经元的变性。

项目成果

Kinoshita A, et al: "Human recombinant superoxide dismutase protects primary cultured neurons against hypoxic injury" Pathobiology. 59. 340-344 (1991)

Kinoshita A 等人：“人类重组超氧化物歧化酶可保护原代培养的神经元免受缺氧损伤”病理生物学。

Yamada K, et al: "Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction" J Cereb Blood Flow Metabol. 11. 472-478 (1991)

Yamada K 等人：“碱性成纤维细胞生长因子可预防皮质梗塞后丘脑变性”J Cereb Blood Flow Metabol。

Kinoshita A,et al: "Wound healing following stub injury on rat cerebral cortex" Neurol Res. 113. 184-188 (1991)

Kinoshita A 等人：“大鼠大脑皮层残端损伤后的伤口愈合”Neurol Res。

Kohmura E,et al: "Neurotoxicity caused by glutamate after subcritical hypoxia is prevented by CNOX: an in vitro study using rat hippocampal neurons" Neurosci Lett. 121. 159-162 (1991)

Kohmura E 等人：“CNOX 可预防亚临界缺氧后谷氨酸引起的神经毒性：一项使用大鼠海马神经元的体外研究”Neurosci Lett。

yamada K,et al: "Modification of ischemic neuronal injury by basic fibroblast growth factor.Ito U,Klatzo I (eds),Maturation Phenomenon" Springer,Tokyo, (1992)

yamada K，等人：“碱性成纤维细胞生长因子对缺血性神经元损伤的修饰。Ito U，Klatzo I（编辑），成熟现象”Springer，东京，（1992）