Mechanism of Ischemic Neuronal Death : Neuron, Glial interaction

缺血性神经元死亡的机制：神经元、胶质细胞相互作用

• 批准号: 07670692
• 负责人: NAKAMURA Shozo
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670692/
• 关键词: ischemia; cytokine; oxidative stress; antioxidant; neurotrophic factor; inflammation; neuronal death; in flammation; oxdiative stress

The present was designed to study (1) glial cell activation, and (2) heparin-binding growth-associated molecule exression after ischemia in order to obtain a clue to prevent ischemia-induced dementia.(1) Induction of stress-activated molecules in the glial cellsMicroglial cells were activated after ischemia and presented various immuno-reactive molecules. Astroglial cells presented stress proteins, such as HSP27. Neutrophils in ischemic areas expressed cell adhesion molecules. These data suggest that chemicals that can intervene immunological processes could be promissing for the treatment of ischemic brain injury.(2) Neurotrophic substances and ischemiaWe focused upon heparin-binding growth-associated molecules (HB-GAM), as HB-GAM shows trophic effects on various types of neurons. We observed that HB-GAM is expressesd in normal CA1 pyramidal neurons. After ischemic death of CA1 neuron, HB-GAM expression in the CA1 subfield was markedly enhanced and reactive astrocytes were the major source of HB-GAM.The level of Syndecan-3, the receptor for HB-GAM,was also altered after ischemia. These results suggest that HB-GAM may play an important role for neuronal survival and synaptic rearrangement.Bifemelane hydrochloride (BF) is a modulator of cholinergic systems and increases muscarinic cholinergic receptor density. Animals treated with BF for one-hundred days after ischemia showed increased cholinesterase activity in the hippocampus. Thus, modulation of cholinergic system could be beneficial for the treatment of post-ischemic brain dysfunction.

目前旨在研究（1）胶质细胞的活化，（2）缺血后肝素结合生长相关的分子外流，以获得防止缺血性痴呆痴呆的线索。（1）在胶质细胞细胞中诱导应激激活分子在脉冲细胞中被激活了各种不受欢迎的分子，并产生了各种不受欢迎的分解。星形胶质细胞呈现应力蛋白，例如HSP27。缺血区域中的中性粒细胞表达细胞粘附分子。这些数据表明，可以干预免疫学过程的化学物质可以为缺血性脑损伤的治疗提供投票。（2）神经营养性物质和缺血性专注于肝素结合生长相关的分子（HB-GAM），因为HB-GAM表现出对各种神经元的营养作用。我们观察到HB-GAM在正常的CA1锥体神经元中表达。 Ca1神经元缺血性死亡后，CA1子场中的HB-GAM表达显着增强，而反应性星形胶质细胞是HB-GAM的主要来源。HB-GAM的受体Syndecan-3水平在缺血后也会改变。这些结果表明，HB-GAM可能对神经元存活和突触重排起重要作用。Bifemelane盐酸盐（BF）是胆碱能系统的调节剂，并增加了毒蕈碱胆碱能受体密度。缺血后用BF治疗的动物在海马中显示胆碱酯酶活性增加。因此，胆碱能系统的调节可能有益于治疗后缺血后脑功能障碍。

项目成果

Takeda A., Kimpara T., Onodera H., Itoyama Y., Kogure K., Shibahara S.: "Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia." Neuroscience Letters. 205. 1-4 (1996)

Takeda A.、Kimpara T.、Onodera H.、Itoyama Y.、Kogure K.、Shibahara S.：“大鼠短暂前脑缺血后血红素加氧酶 1 蛋白诱导的区域差异。”

Kato, H: "Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance" Journal of Cerebral Blood Flow and Metabolism. 15. 60-70 (1995)

Kato，H：“缺血耐受沙鼠模型缺血后海马中超氧化物歧化酶的免疫组织化学定位”《脑血流与代谢杂志》。

Huang Y.L., Onodera H., Takeda A., Itoyama Y., Kogure K.: "The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus." Brain Res.722. 195-199 (1996)

Huang Y.L.、Onodera H.、Takeda A.、Itoyama Y.、Kogure K.：“长期缺血后盐酸比非美烷治疗对沙鼠海马胆碱能系统的影响”。

Kato, H: "Rolipram, a cyclic AMP-selective phosphodiesterase inhibitor, reduces neuronal damage following cerebral ischemia in the gerbil" European Journal of Pharmacology. 272. 107-110 (1995)

Kato, H：“咯利普兰是一种环 AMP 选择性磷酸二酯酶抑制剂，可减少沙鼠脑缺血后的神经元损伤”《欧洲药理学杂志》。

Kato, H.: "An immunohistochemical study of heat shock protein-27 in the hippocampus in a gerbil model of cerebral ischemia and ischemic tolerance" Neuroscience. 68. 65-71 (1995)

Kato, H.：“沙鼠脑缺血和缺血耐受模型海马热休克蛋白 27 的免疫组织化学研究”《神经科学》。