Rothman S
J Neurosci. 1984 Jul;4(7):1884-91. doi: 10.1523/JNEUROSCI.04-07-01884.1984.
The pathophysiology of hypoxic neuronal death, which is difficult to study in vivo, was further defined in vitro by placing dispersed cultures of rat hippocampal neurons into an anoxic atmosphere. Previous experiments had demonstrated that the addition of high concentrations of magnesium, which blocks transmitter release, protected anoxic neurons. These more recent experiments have shown that gamma-D-glutamylglycine (DGG), a postsynaptic blocker of excitatory amino acids, was highly effective in preventing anoxic neuronal death. DGG also completely protected the cultured neurons from the toxicity of exogenous glutamate (GLU) and aspartate (ASP). In parallel physiology experiments, DGG blocked the depolarization produced by GLU and ASP, and dramatically reduced EPSPs in synaptically coupled pairs of neurons. These results provide convincing evidence that the synaptic release of excitatory transmitter, most likely GLU or ASP, mediates the death of anoxic neurons. This result has far-reaching implications regarding the interpretation of the existing literature on cerebral hypoxia. Furthermore, it suggests new strategies that may be effective in preventing the devastating insults produced by cerebral hypoxia and ischemia in man.
缺氧性神经元死亡的病理生理学在体内难以研究，通过将大鼠海马神经元的分散培养物置于缺氧环境中，在体外进一步明确了其机制。先前的实验表明，添加高浓度的镁可阻断递质释放，从而保护缺氧神经元。这些最新实验表明，γ-D-谷氨酰甘氨酸（DGG），一种兴奋性氨基酸的突触后阻滞剂，在预防缺氧性神经元死亡方面非常有效。DGG还能完全保护培养的神经元免受外源性谷氨酸（GLU）和天冬氨酸（ASP）的毒性影响。在平行的生理学实验中，DGG阻断了由GLU和ASP产生的去极化，并显著降低了突触耦合神经元对中的兴奋性突触后电位（EPSP）。这些结果提供了令人信服的证据，表明兴奋性递质的突触释放，很可能是GLU或ASP，介导了缺氧神经元的死亡。这一结果对于解释现有的关于脑缺氧的文献具有深远的意义。此外，它还提出了可能有效预防人类脑缺氧和缺血所产生的毁灭性损伤的新策略。
