Cerebral Carbohydrate Metabolism During Acute Hypoxia and Recovery1

Abstract— The levels of ATP, ADP, AMP and phosphocreatine, of four amino acids, and of 11 intermediates of carbohydrate metabolism in mouse brain were determined after: (1) various degrees of hypoxia; (2) hypoxia combined with anaesthesia; and (3) recovery from severe hypoxia. Glycogen decreased and lactate rose markedly in hypoxia, but levels of ATP and phosphocreatine were normal or near normal even when convulsions and respiratory collapse appeared imminent. During 30 s of complete ischaemia (decapitation) the decline in cerebral ATP and phosphocreatine and the increase in AMP was less in mice previously rendered hypoxic than in control mice. From the changes we calculated that the metabolic rate had decreased by 15 per cent or more during 30 min of hypoxia. Hypoxia was also associated with decreases of cerebral 6‐phosphogluconate and aspartate, and increases in alanine, γ‐aminobutyrate, α‐ketoglutarate, malate, pyruvate, and the lactate :pyruvate ratio. Following recovery in air (10 min), increases were observed in glucose (200 per cent), glucose‐6‐phosphate, phosphocreatine and citrate, and there was a fall in fructose‐1, 6‐diphosphale. Similar measurements were made in samples from cerebral cortex, cerebellum, midbrain and medulla. Severe hypoxia produced significant increases in lactate and decreases in glycogen in all areas; γ‐aminobutyrate levels increased in cerebral cortex and brain stem, but not in cerebellum. No significant changes occurred in ATP and only in cerebral cortex was there a significant fall in phosphocreatine. Phosphocreatine, ATP and glycogen were determined by quantitative histochemical methods in four areas of medulla oblongata , including the physiological respiratory centre of the ventromedial portion. After hypoxia, ATP was unchanged throughout and the changes (decreases) in phosphocreatine and glycogen were principally confined to dorsal medulla, notably the lateral zone. Thus there is no evidence that respiratory failure is caused by a ‘power’ failure in the respiratory centre. It is suggested that in extremis a protective mechanism may cause neurons to cease firing before high‐energy phosphate stores have been exhausted.