Roles of astroglial energy metabolism in ischemic neuronal cell damage: an implication for the treatment of cerebral ischemia

1)电压敏感钠通道的持续激活导致Na^+内流到培养的大鼠神经元中，引起神经元细胞损伤。钠离子载体也可诱导Na^+诱导的神经元损伤。2) Na^+内流通过线粒体功能障碍导致星形胶质细胞损伤。Na^+内流诱导星形胶质细胞损伤的机制与神经元不同。3) 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）还原被解释为指示细胞代谢活性。星形胶质细胞的MTT特异性活性明显高于神经元。在星形胶质细胞中，MTT还原主要反映胞质氧化还原活性，并依赖于甘油醛3-磷酸脱氢酶。在神经元中，丙酮酸脱氢酶比葡萄糖或乳酸更有效地支持MTT还原，尽管这两种底物都能产生NADH和丙酮酸。葡萄糖是大脑的唯一能量来源。在大脑中，只有星形胶质细胞能将葡萄糖储存为细胞内糖原，并在葡萄糖供应有限时利用它。我们在培养的大鼠星形胶质细胞中检测了急性或慢性暴露于葡萄糖耗尽状态对细胞内糖原含量和细胞能量代谢指标Alamar Blue的减少的影响。所获得的结果表明，当细胞外葡萄糖和细胞内糖原不可用时，星形胶质细胞能量的产生更加依赖于TCA循环。

1) Persistent activation of voltage-sensitive sodium channels results in Na^+ influx into rat cultured neurons and induces neuronal cell damage. Sodium ionophore also induces Na^+ -induced neuronal damage.2) Na^+ influx causes astroglial cell damage via its mitochondrial dysfunction. The mechanism by which Na^+ influx induces cell damage in astroglia is different from that in neurons.3) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is interpreted to be indicative of cellular metabolic activity. MTT specific activity of astroglia was much higher than that of neurons. In astroglia, MTT reduction reflects mainly cytosolic redox activity and is dependent on glyceraldehyde 3-phosphate dehydrogenase. In neurons, pyruvate dehydrogenase supports MTT reduction more effectively than glucose or lactate, even though both of these substrates can produce NADH and pyruvate.4) Glucose is the sole energy source of the brain. In brain, only astrocytes can store glucose as intracellular glycogen and utilize it when glucose supply is limited. We examined the effect of acute or chronic exposure to glucose depleted condition on intracellular glycogen content and the reduction of Alamar Blue, an indicator of cellular energy metabolism, in rat cultured astroglia. Obtained results suggest that astroglial energy production becomes more dependent on the TCA cycle when extracellular glucose and intracellular glycogen are not available.