INCREASED BRAIN GLUCOSE AND GLYCOGEN AFTER HYDROCORTISONE: MECHANISMS OF ACTION

We have previously reported that in young mice hydrocortisone (100 mg/kg s.c. from 10 to 20 days of age) doubled brain glucose (J. Neurochem. 16:107, 1969). Possible explanations were increased glucose transport from the blood to the brain or decreased glucose utilization by the brain. In this study brain metabolism was estimated from the rate of fall of total available and potential high energy phosphate after decapitation (O.H. Lowry, et al., J. Biol. Chem. 239:18, 1964). 5 litters of mice (treated as above) were either frozen whole in liquid N2 or decapitated and the heads frozen after 15 and 30 sec. Zero time hydrocortisone mice had significantly elevated brain glucose (56%, p < 0.001) and glycogen (16%, p = 0.004). Brain ATP, P-creatine and lactate were unchanged. The fall of high energy phosphate during 30 sec. of ischemia was 6.63 mmoles/kg in controls and 6.44 mmoles/kg in hydrocortisone treated animals indicating no change in cerebral metabolic rate. The brain to plasma glucose ratio, an index of glucose transport when the metabolic rate is normal, was 90% higher in the hydrocortisone animals, namely 0.207 vs. 0.109 in controls. Other explanations for the increased glucose and glycogen, such as inhibition of the pentose phosphate pathway and (although less likely) increased gluconeogenesis as in other tissues after hydrocortisone, are currently under investigation.