Thurston J H, Hauhart R E, Dirgo J A, Jones E M
Ann Neurol. 1980 Jun;7(6):515-23. doi: 10.1002/ana.410070604.
We reported previously that chronic administration of hydrocortisone to normal developing mice increases the brain glucose content and cerebral energy reserve. The present report concerns possible mechanisms of this action. Increases in brain glucose (and glycogen) levels were not due to reduction of cerebral metabolic rate, and the effect of hydrocortisone in facilitating transport of hexose from blood to brain was not impressive. Chronic hydrocortisone treatment induced increases in the activities of brain glycerophosphate dehydrogenase and pyruvate carboxylase in vivo; there was no effect on eleven other enzymes of brain glucose and glycogen metabolism. In normal nursing mice, hydrocortisone produced consistent elevations in plasma beta-hydroxybutyrate (and glycerol) levels. Brain beta-hydroxybutyrate levels were also increased. Therefore, the brain glucose concentration may be elevated in these animals because of the availability of an increased supply of ketone bodies as alternative substrates for cerebral oxidative metabolism and biosynthesis. Ketonemia, elevated cerebral glucose and beta-hydroxybutyrate concentrations, and increased glycerophosphate dehydrogenase activity in brain suggest possible explanations for the beneficial action of adrenocorticotropic hormone and glucocorticoids in the treatment of infantile myoclonic epilepsy and other neurological disorders.
我们之前报道过，对正常发育的小鼠长期给予氢化可的松会增加脑葡萄糖含量和脑能量储备。本报告关注这种作用的可能机制。脑葡萄糖（和糖原）水平的升高并非由于脑代谢率降低，且氢化可的松促进己糖从血液转运至脑的作用并不显著。长期给予氢化可的松治疗可诱导体内脑甘油磷酸脱氢酶和丙酮酸羧化酶的活性增加；对脑葡萄糖和糖原代谢的其他十一种酶没有影响。在正常哺乳小鼠中，氢化可的松使血浆β-羟基丁酸酯（和甘油）水平持续升高。脑β-羟基丁酸酯水平也升高。因此，这些动物的脑葡萄糖浓度可能升高是因为有增加的酮体供应作为脑氧化代谢和生物合成的替代底物。酮血症、升高的脑葡萄糖和β-羟基丁酸酯浓度以及脑中甘油磷酸脱氢酶活性增加提示了促肾上腺皮质激素和糖皮质激素在治疗婴儿肌阵挛性癫痫和其他神经系统疾病中有益作用的可能解释。
