Auer R N
Stroke. 1986 Jul-Aug;17(4):699-708. doi: 10.1161/01.str.17.4.699.
The central question to be addressed in this review can be stated as "How does hypoglycemia kill neurons?" Initial research on hypoglycemic brain damage in the 1930s was aimed at demonstrating the existence of any brain damage whatsoever due to insulin. Recent results indicate that uncomplicated hypoglycemia is capable of killing neurons in the brain. However, the mechanism does not appear to be simply glucose starvation of the neuron resulting in neuronal breakdown. Rather than such an "internal catabolic death" current evidence suggests that in hypoglycemia, neurons are killed from without, i.e. from the extracellular space. Around the time the EEG becomes isoelectric, an endogenous neurotoxin is produced, and is released by the brain into tissue and cerebrospinal fluid. The distribution of necrotic neurons is unlike that in ischemia, being related to white matter and cerebrospinal fluid pathways. The toxin acts by first disrupting dendritic trees, sparing intermediate axons, indicating it to be an excitotoxin. Exact mechanisms of excitotoxic neuronal necrosis are not yet clear, but neuronal death involves hyperexcitation, and culminates in cell membrane rupture. Endogenous excitotoxins produced during hypoglycemia may explain the tendency toward seizure activity often seen clinically. The recent research results on which these findings are based are reviewed, and clinical implications are discussed.
本综述要探讨的核心问题可表述为“低血糖是如何杀死神经元的？”20世纪30年代关于低血糖脑损伤的初步研究旨在证明胰岛素导致任何脑损伤的存在。最近的研究结果表明，单纯性低血糖能够杀死大脑中的神经元。然而，其机制似乎并非仅仅是神经元因葡萄糖饥饿而导致神经元分解。与这种“内部分解代谢死亡”不同，目前的证据表明，在低血糖状态下，神经元是从外部，即细胞外空间被杀死的。在脑电图变为等电位时，一种内源性神经毒素产生，并由大脑释放到组织和脑脊液中。坏死神经元的分布与缺血时不同，与白质和脑脊液通路有关。该毒素首先通过破坏树突而发挥作用，中间轴突则不受影响，表明它是一种兴奋性毒素。兴奋性毒性神经元坏死的确切机制尚不清楚，但神经元死亡涉及过度兴奋，并最终导致细胞膜破裂。低血糖期间产生的内源性兴奋性毒素可能解释了临床上常见的癫痫发作倾向。本文回顾了这些发现所基于的最新研究成果，并讨论了其临床意义。
