Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal cell death.

缺血性神经元细胞死亡的发生机制和针对缺血性神经元细胞死亡的保护。

• 批准号: 14572088
• 负责人: TAMURA Yutaka
• 金额: $ 2.24万
• 依托单位: Fukuyama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572088/
• 关键词: adenosine; dementia; gerbil; ischemia; neuroprotection; primary culture; adenosine; AMP; ATP; A1 receptor; cortex; culture; glutamte; necrosis

Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal cell death were examined by using ischemic animal model and primary culture.Transient bilateral carotid occlusion in gerbil caused a selective delayed degeneration of the pyramidal neurons in the CA1 hippocampal area. This selective damage was attenuated by MK-801, a NMDA receptor antagonist and L-NAME, a nitric oxide synthase inhibitor. Moreover, CHA, an adenosine A1 receptor antagonist and CGS-21680, an adenosine A2 receptor antagonist, were also effective in protection of CA1 pyramidal neurons.The neuronal cell death caused, when the primary culture cell was incubated in hypoxia and hypoglycemia solution. This cell death was attenuated by treatment of MK-801, L-NAME, adenosine, CHA and CGS-21680. CHA reduced hypoxia/hypoglycemia-induced elevation of intracellular Ca2+ level. Neuroprotective effects of CGS-20680 was attenuated by H-89, a protein kinase A inhibitor.These results indicate that adenosine is endogenous neuroprotection substance against ischemic neuronal cell death. Moreover, this results rise the possibility that adenosine becomes a drug for the dementia induced by vascular damage.

采用沙土鼠脑缺血动物模型和原代培养方法，探讨了沙土鼠脑缺血后神经细胞死亡的发生机制及其对脑缺血的保护作用。这种选择性损伤可被N-甲基-D-天冬氨酸受体拮抗剂MK-801和一氧化氮合酶抑制剂L-NAME所减弱。此外，腺苷A1受体拮抗剂CHA和腺苷A2受体拮抗剂CGS-21680对CA1区锥体神经元也有保护作用。MK801、L-NAME、腺苷、CHA和CGS-21680可减轻这种细胞死亡。CHA可降低缺氧/低血糖引起的细胞内钙离子水平的升高。CGS-20680的神经保护作用可被蛋白激酶A抑制剂H-89减弱，这一结果表明腺苷是一种内源性神经保护物质，可对抗缺血性神经细胞死亡。此外，这一结果增加了腺苷成为治疗血管损伤所致痴呆的药物的可能性。