The molecular phamacological study of the interaction of neuro-immune system

神经免疫系统相互作用的分子药理学研究

• 批准号: 08457602
• 负责人: NOMURA Yasuyuki
• 金额: $ 5.57万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457602/
• 关键词: brain ischemia; neuronal apoptosis; glial cells; cytokine; 胸腺細胞; リンパ球; アセチルコリン受容体; カルシトニン; 核内転写因子

Inflammatory/immnological processes underlie survival/damage of meurons after brain ischemia. It is not clear whether or not the neuronal death after brain ischemia is apoptosis or necrosis. Under the condition of transient forebrain ischemia, we obtained results suggesting apoptosis in the delayd neuronal death of the CA1 pyramidal neurons.In glia ; cells, cytokines such as IL-1beta asnd TNF-alpha are produced following ischemic stresses. On the other hand, it is suggested that NO/iNOS is involved in neuronal apoptosis. The iNOS induction was detected primarily in astrocytes after the transient forebrain ischemia when the neuronal apoptosis was observed. In the[next series, we examined whether cytokines and chemokines were produced after the brain ischemia. The transient expressions of mRNA of IL-6 and CINC were observed after the transient forebrain ischemia in the cerebral cortex and the hippocampus. IL-6 is known as a survival factor for neurons. It is, therefore, suggested that IL-6 may play a role as a protective factor against ischemic stress. The precise roles of NO,cytokines and chemokines on brain ischemic insult are an interesting subject to be elucidated.

炎症/免疫过程是脑缺血后神经元存活/损伤的基础。脑缺血后神经元的死亡是凋亡还是坏死尚不清楚。在短暂性前脑缺血的条件下，我们得到的结果表明，在CA 1锥体神经元的延迟性神经元死亡的凋亡，在胶质细胞中，细胞因子，如IL-1 β和TNF-α产生后，缺血应激。另一方面，NO/iNOS参与了神经细胞凋亡。短暂性前脑缺血后，诱导型一氧化氮合酶主要表达于星形胶质细胞，同时可见神经元凋亡。在接下来的系列研究中，我们检测了脑缺血后是否产生细胞因子和趋化因子。短暂性前脑缺血后，大脑皮层和海马可见IL-6和CINC mRNA的瞬时表达。IL-6被认为是神经元的存活因子。因此，IL-6可能作为抗缺血应激的保护因子发挥作用。NO、细胞因子和趋化因子在脑缺血损伤中的确切作用是一个有待阐明的有趣课题。

项目成果

Yoshinaga, N.et al: "Death by a deparminergic neurotoxin, 1-methy-4-phenylpyridinium Ion MMP^+ and protection by EFG in GH3 cells." Brain Res.(in press).

Yoshinaga, N.等人：“在 GH3 细胞中，脱巴胺能神经毒素 1-甲基-4-苯基吡啶鎓离子 MMP^ 导致死亡，并受到 EFG 的保护。”

Nomura Yasuyuki: Induction of nitric oxide synthese in astrocytes and neuronal death 「Progress in Research on Brain Function」 (de. by Norio Akaike). Press of Kyushu University (in press),

野村康之：星形胶质细胞中一氧化氮合成的诱导和神经元死亡“脑功能研究进展”（赤池纪夫撰）（出版中），

野村 靖幸: "グリア細胞由来のNO" 中外医学社(印刷中),

Yasuyuki Nomura：“NO源自神经胶质细胞”Chugai Igakusha（正在出版），

Yasuyuki Nomura: "Neuronal apoptosis by glial NO : involvement of inhibition of glyceraldehyde-3-phosphatedehydrogenase." Human Cell. 9(3). 205-214 (1996)

Yasuyuki Nomura：“神经胶质细胞 NO 导致的神经细胞凋亡：涉及 3-磷酸甘油醛脱氢酶的抑制。”

Yasuyuki Nomura: "Senescence accelerated mouse : Neurochemicl studies on aging." Annals of the New-York Academy of Sciences, 9 (1996)

Yasuyuki Nomura：“衰老加速的小鼠：衰老的神经化学研究。”