Stecker M M, Stevenson M R
Winthrop University Hospital, Mineola, NY 11530, United States.
Winthrop University Hospital, Mineola, NY 11530, United States.
Neuroscience. 2015 Jan 22;284:653-667. doi: 10.1016/j.neuroscience.2014.10.048. Epub 2014 Nov 4.
Hyperglycemia accentuates the injury produced by anoxia both in the central and peripheral nervous system. To understand whether this is a consequence of changes in metabolic pathways produced by anoxia, the effect of the metabolic substrate used by the rat peripheral nerve on the nerve action potential (NAP) was studied in the presence and absence of anoxia. In the continuously oxygenated state, the NAP was well preserved with glucose, lactate, as well as with high concentrations of sorbitol and fructose but not β-hydroxybutyrate, acetate or galactose. With intermittent anoxia, the pattern of substrate effects on the NAP changed markedly so that low concentrations of fructose became able to support neurophysiologic activity but not high concentrations of glucose. These alterations occurred gradually with repeated episodes of anoxia as reflected by the progressive increase in the time needed for the NAP to disappear during anoxia when using glucose as substrate. This "preconditioning" effect was not seen with other substrates and an opposite effect was seen with lactate. In fact, the rate at which the NAP disappeared during anoxia was not simply related to degree of recovery after anoxia. These are distinct phenomena. For example, the NAP persisted longest during anoxia in the setting of hyperglycemia but this was the state in which the anoxic damage was most severe. Correlating the results with existing literature on the metabolic functions of Schwann cells and axons generates testable hypotheses for the mechanism of hyperglycemic damage during anoxia and lead to discussions of the role for a metabolic shuttle between Schwann cells and axons as well as a potential important role of glycogen.
高血糖会加重中枢神经系统和周围神经系统因缺氧而产生的损伤。为了了解这是否是缺氧引起的代谢途径变化的结果，研究了在有缺氧和无缺氧情况下，大鼠周围神经所使用的代谢底物对神经动作电位（NAP）的影响。在持续有氧状态下，葡萄糖、乳酸以及高浓度的山梨醇和果糖能很好地保存NAP，但β-羟基丁酸、乙酸或半乳糖则不能。在间歇性缺氧时，底物对NAP的影响模式发生了明显变化，以至于低浓度的果糖能够支持神经生理活动，而高浓度的葡萄糖则不能。这些变化随着缺氧的反复发生而逐渐出现，这一点通过以葡萄糖为底物时，缺氧期间NAP消失所需时间的逐渐增加得以体现。其他底物未观察到这种“预处理”效应，而乳酸则呈现相反的效应。事实上，缺氧期间NAP消失的速率并不简单地与缺氧后的恢复程度相关。这些是不同的现象。例如，在高血糖情况下，NAP在缺氧期间持续时间最长，但这却是缺氧损伤最严重的状态。将这些结果与关于施万细胞和轴突代谢功能的现有文献相关联，就产生了关于缺氧期间高血糖损伤机制的可测试假设，并引发了对施万细胞和轴突之间代谢穿梭作用以及糖原潜在重要作用的讨论。
