Survival after 5 min of anoxia in 39 controls (8-12-day-old mice) was only 5% compared with 82y0 in 39 glucose-treated littermates. Even after decapitation there was a delay in the onset of terminal gasping in the isolated heads of glucose-treated animals (P = 0.03) and the last gasp occurred much later than in the heads of control animals ( P < 0.001). To study the mechanism of this phenomenon mice were injected with 30 mmol/kg glucose subcutaneously. Control animals were given equiosmolal amounts of NaC1. One hour later the animals were exposed to nitrogen gas (0 pressure < 5 mm Hg). In glucose-treated mice the initial glucose concentration in brain was 3 times the control value ( P < 0.001). ATP, P-creatine, and glycogen levels were unchanged.Although the rate of use of these compounds during anoxia was similar in both groups of mice, the high level of glucose in brain in glucose-treated mice permitted considerable sparing of these energy-yielding metabolites. In terms of actual and potential molar equivalents of high energy phosphate (NP), the brain energy reserve after 4 min of anoxia in glucose-treated animals was twice that of controls, 10.70 =t 0.72 versus 4.75 =t 1.19 mmol/kg ( P = 0.009). SpeculationDuring acute anoxia, concentration of glucose in brains of young animals is critically reduced, although levels of glucose in plasma remain normal or may even become elevated. Pretreatment or concurrent administration of glucose increases anoxic survival. Because glucose has this dramatic life-saving effect in anoxic animals, the possibility that inadequate brain glucose supplies may occur in anoxic man in the face of normal or elevated levels of glucose in plasma should be considered. Introductionglucose in brain fell 80% and 60%, respectively [lo],

ExtractAnoxia was produced in 34 mice less than 12 hr of age by exposure to N 2 at 37° (P o , less than 5 mm Hg). Although brain glucose levels fell from the normal value of 0.60 ± 0.14 mmol/kg to 0.22 ± 0.04 mmol/kg after 6 min of anoxia, in the livers of the same animals there was a fourfold increase in glucose concentration from 2.61 ± 0.28 mmol/kg to 10.45 ± 0.45. In 22 other animals of the same age plasma glucose levels increased from 3.04 ± 0.03 mM to 5.56 ± 1.09 mM during this interval of anoxia. Further studies concerned the mechanism of this unexpected independence of blood and brain glucose values during anoxia.During the 6 min of anoxia brain lactate increased 7.49 mmol/kg. This increase is more than twice that accounted for by the total decrease in brain glucose and glycogen. One explanation for this finding is an increased uptake of glucose from the blood by the brain. If so, the rate of glucose influx is almost 5 times that reported for newborn mice with an adequate O2 supply. Another possibility is a transport or diffusion of lactate from the blood to the brain. However, a study of the effect of lactate administration on levels of lactate in plasma and brain of 17 newborn mice suggests that permeation of the blood-brain barrier to lactate is a less likely explanation. Inasmuch as glycolysis increases 10-fold in ischemic brain of the neonatal mouse, it appears that brain glucose decreases in these animals because the demand for glucose during anoxia exceeds the supply.

Louis. Brief f a s t i n g r a i s e s the convulsive threshold i n t h e human. This c l i n i c a l observation led t o the use of a ketogenic d i e t i n epilepsy. To study the mechanism underlying t h i s observat i o n , the electroconvulsive threshold (ECT) of adult r a t s was determined before f a s t i n g and a t 24, 48 and 72 hours a f t e r food deprivation. The ECT was unchanged a t 24 hours, r i s i n g a t 48 hours (p < .05) and 72 hours (p < .01). During starvat i o n blood glucose l e v e l s f e l l and blood ketone bodies rose with s i m i l a r changes, respectively, i n brain t i s s u e . Brain sodium l e v e l s were s l i g h t l y higher a t 24 and 72 hours and unchanged a t 48 hours whereas b r a i n potassium l e v e l s gradually rose a t 48 hours (p < . l o ) and a t 72 hours (p < .025). Brain water content was r e l a t i v e l y constant. Ouabain s e n s i t i v e and i n s e n s i t i v e ATPase a c t i v i t remained unchanged. Glucose-6-phosphate l e v e l s rose a t 42; and 72 hours whereas malate f e l l progressively throughout f a s t i n g . Lactate and p y r w a t e l e v e l s f e l l i n i t i a l l y then rose and t h e LIP r a t i o f e l l s t e a d i l y from 12.7 t o 10.9. The adenylate pool and P i remained constant but the cerebral energy charge p o t e n t i a l and the phosphorylation s t a t e rose a t 48 and 72 hours (p < .05). The c e r e b r a l energy reserve remained constant. These observed changes a r e f e l t t o be the consequence of increasing u t i l i z a t i o n of ketone bodies f o r cerebral oxidative metabolism with a secondary depression i n glycolysis. The r i s e i n brain potassium may ref l e c t t h i s increased u t i l i z a t i o n of anions and explain the r i s e i n the electroconvulsive threshold.