Delayed rescue of N-methyl-D-aspartate receptor-mediated neuronal injury in cortical culture.
Delayed rescue of N-methyl-D-aspartate receptor-mediated neuronal injury in cortical culture.
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发表时间：
1989-08
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通讯作者：
Dean M. Hartley;D. Choi
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作者：
Dean M. Hartley;D. Choi
本研究探讨了神经保护作用的延迟操作完成后，兴奋性中毒的侮辱。许多培养的小鼠皮层神经元，否则会死亡后，暴露于500 μ M的N-甲基-D-天冬氨酸（NMDA）或谷氨酸可以挽救后期加入NMDA拮抗剂的浴介质。D-2-氨基-5-膦酰基戊酸酯（D-APV）、MK-801（5-甲基-10，11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺马来酸酯）和右啡烷均产生浓度依赖性神经保护作用，EC 50分别约为10、0.3和3 μ M，疗效相似。注定的神经元群体，可以挽救的分数取决于洗脱的NMDA和拮抗剂添加之间的时间间隔，开始在最大的40至80%，立即添加，并衰减到零后30分钟。D-APV只需要存在30分钟的近最大保护。NMDA拮抗剂拯救注定的神经元的能力没有被几种其他药物模仿：1 mM γ-D-谷氨酰-氨基甲基磺酸盐，1 mM L-谷氨酸二乙酯，10 μ M 6-硝基-7-氰基-喹喔啉-2，3-二酮，1 mM司可巴比妥，100 μ M二苯基乙内酰脲，10 μ M硝苯地平或3 μ M河豚毒素。广谱谷氨酸拮抗剂犬尿氨酸具有与D-APV类似的保护作用，但当加入D-APV时，并没有改善神经保护作用。神经元也可以通过延迟去除细胞外钙30分钟后，暴露于NMDA的拯救。相反，用胆碱替代钠实际上增强了所产生的神经元损伤。（250字处删节）
The present study explored the neuroprotective efficacy of delayed manipulations performed after completion of an excitotoxic insult. Many cultured murine cortical neurons that would otherwise die after exposure to 500 microM N-methyl-D-aspartate (NMDA) or glutamate could be rescued by the late addition of NMDA antagonists to the bathing medium. D-2-Amino-5-phosphonovalerate (D-APV), MK-801 (5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate) and dextrorphan all produced concentration-dependent neuroprotection, with EC50 about 10, 0.3 and 3 microM, respectively, and similar efficacy. The fraction of the doomed neuronal population that could be rescued depended on the time interval between washout of NMDA and antagonist addition, starting at a maximum of 40 to 80% with immediate addition, and decaying to zero after 30 min. D-APV only needed to be present for 30 min for near maximal protection. The ability of NMDA antagonists to rescue doomed neurons was not mimicked by several other drugs: 1 mM gamma-D-glutamyl-aminomethyl sulfonate, 1 mM L-glutamate diethyl ester, 10 microM 6-nitro-7-cyano-quinoxaline-2,3-dione, 1 mM secobarbital, 100 microM diphenylhydantoin, 10 microM nifedipine or 3 microM tetrodotoxin. The broad spectrum glutamate antagonist kynurenate had a protective action similar to that of D-APV, but when added to D-APV did not improve neuroprotection. Neurons could also be rescued by the delayed removal of extracellular calcium for 30 min after exposure to NMDA. In contrast, replacement of sodium with choline actually enhanced resultant neuronal damage.(ABSTRACT TRUNCATED AT 250 WORDS)