Grabb M C, Choi D W
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci. 1999 Mar 1;19(5):1657-62. doi: 10.1523/JNEUROSCI.19-05-01657.1999.
Murine cortical cultures containing both neurons and glia (days in vitro 13-15) were exposed to periods of oxygen-glucose deprivation (5-30 min) too brief to induce neuronal death. Cultures "preconditioned" by sublethal oxygen-glucose deprivation exhibited 30-50% less neuronal death than controls when exposed to a 45-55 min period of oxygen-glucose deprivation 24 hr later. This preconditioning-induced neuroprotection was specific in that neuronal death induced by exposure to excitotoxins or to staurosporine was not attenuated. Neuroprotection was lost if the time between the preconditioning and severe insult were decreased to 7 hr or increased to 72 hr and was blocked if the NMDA antagonist 100 microM 3-((D)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid was applied during the preconditioning insult. This was true even if the duration of preconditioning was increased as far as possible (while still remaining sublethal). A similar preconditioning effect was also produced by sublethal exposure to high K+, glutamate, or NMDA but not to kainate or trans-1-aminocyclopentane-1, 3-dicarboxylic acid.
含有神经元和神经胶质细胞的小鼠皮质培养物（体外培养13 - 15天）暴露于氧糖剥夺期（5 - 30分钟），该时长过短以至于不会诱导神经元死亡。经亚致死性氧糖剥夺“预处理”的培养物在24小时后暴露于45 - 55分钟的氧糖剥夺期时，其神经元死亡比对照组少30 - 50%。这种预处理诱导的神经保护作用具有特异性，即暴露于兴奋性毒素或星形孢菌素所诱导的神经元死亡并未减弱。如果预处理与严重损伤之间的时间间隔缩短至7小时或延长至72小时，神经保护作用就会丧失；如果在预处理损伤期间应用NMDA拮抗剂100微摩尔3 - （（D） - 2 - 羧基哌嗪 - 4 - 基） - 丙基 - 1 - 膦酸，神经保护作用就会被阻断。即便预处理的持续时间尽可能延长（仍保持亚致死状态），情况依然如此。亚致死性暴露于高钾、谷氨酸或NMDA也会产生类似的预处理效果，但暴露于海人藻酸或反式 - 1 - 氨基环戊烷 - 1,3 - 二羧酸则不会产生这种效果。
