Decrease in Brain Glucose in Anoxia in Spite of Elevated Plasma Glucose Levels

Abstract

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.

Anoxia in Mice: Reduced Glucose in Brain with Normal or Elevated Glucose in Plasma and Increased Survival after Glucose Treatment

“…In human beings, measurements of the concentration of glucose in the blood are often used to exclude hypoglycemia as a cause of abnormal neurologic signs and symptoms. However, from the present experiments and those ~-eported previously [6], it appears that normal or even elevated glucose levels in the blood cannot be assumed to indicate adequate amounts of glucose in the brain. Although the beneficial effects of glucose pretreatment in mice exposed to anoxia are unequivocal, neither the clinical nor the biochemical data permit a distinction between the relative roles of the cardiovascular system and the increased cerebral energy reserve in increasing survival.…”

“…Similar changes occur in the brains of intact newborn [6] and 10-day-old mice during anoxia and in those of adult mice [3]. T h e mechanism of the increase in glycolysis in anoxic brain, the so-called "Pasteur effect," is now well understood [l, 2,[11][12][13].…”

“…Oxygen deprivation is another example of this unexpected paradox. During 6 min of anoxia at 37", glucose in brain in intact newborn mice fell 72%, whereas, in the same interval, glucose concentration in plasma doubled [6]. In 10-day-old animals, levels of glucose in brain were nearly zero after 2 min of anoxia at 24", and yet no changes in glucose concentration in plasma were seen even after 4 rnin (see Results).…”

“…Because the experiments i n the newborn mice were performed at 37" and the 10-day-old mice were studied at room temperature, no age comparisons can be made. We have studied the mechanism of the paradox of reduced glucose in brain despite elevated concentration of glucose in plasma during anoxia in newborn mice [6]. In the neonate the increase in lactate in brain during 6 min of anoxia was more than twice that expected from the combined decreases in concentration of glucose and glycogen in brain.…”

Neonatal Seizures in Monkeys and Rabbits: Brain Glucose Depletion in the Face of Normoglycemia, Prevention by Glucose Loads

“…It was associated with more severe CNS damage following total asphyxia in the term monkey fetus (13,14), and did not alter the outcome of neonatal hypoxia-ischemia (15). In contrast, hyperglycemia reduced the mortality rate of immature rodents during prolonged convulsions (2) and anoxic anoxia (16,17). Presumably the harmful effects of hyperglycemia in ischemia or asphyxia arise from the local lactic acidosis.…”