Sturm C D, Frisella W A, Yoon K W
Division of Neurosurgery, St. Louis University School of Medicine, Missouri.
J Neurosurg. 1993 Jul;79(1):111-5. doi: 10.3171/jns.1993.79.1.0111.
Glutamate has been shown to play an important role in delayed neuronal cell death occurring due to ischemia. Attenuation of synaptically released glutamate can be accomplished by modulators such as adenosine and baclofen. This study focused on the ability of adenosine to attenuate the excitotoxicity secondary to glutamate receptor activation in vitro after exposure to potassium cyanide (KCN) in hippocampal neuronal cell cultures. For this study, hippocampal cell cultures were obtained from 1-day-old rats and trypan blue staining was used for assessment of cell viability. It was found that the N-methyl-D-aspartate-specific antagonist MK801 (10 microM) attenuated neuronal cell death resulting from exposure to 1 mM KCN for 60 minutes. Adenosine (10 to 1000 microM) decreased neuronal cell death secondary to the same concentration of KCN in a dose-dependent manner. This same neuroprotective effect is mimicked by the adenosine A1-specific receptor agonist N6-cyclopentyladenosine (10 microM). The A1-specific receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (10 to 1000 nM) blocked the neuroprotective effect of adenosine in a dose-dependent manner. Therefore, neuronal cell death produced by KCN in the experimental model described was mediated at least in part by glutamate. This neuronal cell death was attenuated by adenosine via the A1-specific mechanism.
谷氨酸已被证明在因缺血导致的迟发性神经元细胞死亡中起重要作用。突触释放的谷氨酸的衰减可通过腺苷和巴氯芬等调节剂来实现。本研究聚焦于腺苷在海马神经元细胞培养物中暴露于氰化钾（KCN）后，在体外减弱谷氨酸受体激活继发的兴奋性毒性的能力。在本研究中，从1日龄大鼠获取海马细胞培养物，并使用台盼蓝染色评估细胞活力。发现N-甲基-D-天冬氨酸特异性拮抗剂MK801（10微摩尔）可减弱因暴露于1毫摩尔KCN 60分钟所导致的神经元细胞死亡。腺苷（10至1000微摩尔）以剂量依赖方式减少相同浓度KCN继发的神经元细胞死亡。腺苷A1特异性受体激动剂N6-环戊基腺苷（10微摩尔）模拟了相同的神经保护作用。A1特异性受体拮抗剂8-环戊基-1,3-二甲基黄嘌呤（10至1000纳摩尔）以剂量依赖方式阻断了腺苷的神经保护作用。因此，在所述实验模型中，KCN所产生的神经元细胞死亡至少部分由谷氨酸介导。这种神经元细胞死亡通过腺苷经由A1特异性机制而减弱。
