HYPOXIC INJURY TO DEVELOPING GLIAL-CELLS - PROTECTIVE EFFECT OF HIGH GLUCOSE
HYPOXIC INJURY TO DEVELOPING GLIAL-CELLS - PROTECTIVE EFFECT OF HIGH GLUCOSE
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DOI：
10.1203/00006450-199002000-00020
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发表时间：
1990-02-01
影响因子：
3.6
通讯作者：
VOLPE, JJ
中科院分区：
文献类型：
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作者：
CALLAHAN, DJ;ENGLE, MJ;VOLPE, JJ
脑室周围白质软化症是早产儿的主要缺氧缺血性损害，缺氧损伤对分化的胶质细胞是一个关键事件。本研究探讨了低氧对神经胶质细胞分化的影响，主要是星形胶质细胞。使用分离的新生大鼠脑的原代培养，主要由分化的星形胶质细胞组成。乳酸脱氢酶的外流是一种富含星形胶质细胞的酶，用于定量细胞损伤。报告了三个主要发现。首先，分化中的星形胶质细胞对低氧损伤具有较强的耐受性，但在低氧24小时后，细胞损伤明显(乳酸脱氢酶外流占细胞总数的86%，细胞形态发生改变)。当培养液中葡萄糖浓度从约5.6 mM增加到15 mM时，对缺氧有明显的保护作用，即在15 mM葡萄糖中缺氧24 h，乳酸脱氢酶外流完全被阻止。第三，高糖的保护作用似乎与糖酵解增加利用有关，因为细胞对低氧损伤的抵抗力与细胞产生的乳酸和消耗的葡萄糖量直接相关。因此，乳酸脱氢酶外流最低(和葡萄糖补充量最高)的细胞具有高达32-36 mM的中等乳酸浓度。这些乳酸浓度大约是报道的乳酸阈值浓度的两倍，在体内缺氧损伤模型中，主要是在成熟动物中，乳酸被认为会导致细胞坏死。这些数据增加了通过增加葡萄糖供应来预防或改善对分化胶质细胞的缺氧性损伤的可能性。
Hypoxic injury to differentiating glial cells is a critical event in the development of periventricular leukomalacia, the major hypoxic-ischemic lesion of the premature infant. This study has addressed the effects of hypoxia on differentiating glial cells, primarily astrocytes. Primary cultures of dissociated newborn rat brain, which are composed predominantly by differentiating astroglia, were used. Efflux of lactate dehydrogenase, an enzyme enriched in astroglia, was used to quantitate cellular injury. Three major findings are reported. First, differentiating astorcytes were resistant to hypoxic injury for many hours, although by 24 h of hypoxia severe cellular injury (lactate dehydrogenase efflux of 86% of total and morphologic changes) was obvious. Second, increase of glucose in the culture medium from the approximately physiological concentration of 5.6 to 15 mM had a marked protective effect versus hypoxia, i.e. lactate dehydrogenase efflux was totally prevented during 24 h of hypoxia in 15 mM glucose. Third, the protective effect of high glucose appeared to be related to increased utilization by glycolysis, because there was a direct correlation between the resistance to hypoxic cellular injury and the amount of lactate generated and of glucose consumed by the cells. Thus, the cells with the lowest lactate dehydrogenase efflux (and highest glucose supplementations) had medium lactate concentrations as high as 32-36 mM. These concentrations of lactate are approximately double the reported threshold concentration of lactate considered to produce cellular necrosis in in vivo models of hypoxic injury, primarily in mature animals. The data raise the possibility that hypoxic injury to differentiating glia can be prevented or ameliorated by increase in glucose availability.