Cerebral Metabolic Intermediate Response following Severe Canine Intrauterine Growth Retardation

Abstract

ABSTRACT. The effect of intrauterine growth retardation and neonatal hypoglycemia on cerebral metabolic intermediates were determined in newborn dogs subjected to 5 days of maternal canine starvation (MCS) before birth.Birth weight was reduced 23% (232 + 6 versus 300 f 10 g). Circulating blood glucose was reduced after 3 h of neonatal fasting in MCS pups (2.7 f 0.4 f versus 5.7 + 1.1 mM). Cerebral cortical levels of glucose were also reduced at this time. Cerebral glucose-6-phosphate was not altered; nonetheless fructose-6-phosphate was lower in MCS pups at 6 and 9 h, while fructose 1,6-diphosphate appeared elevated at 3 h. These data suggest that cerebral glycolytic activity may be increased by increased activity of phosphofructokinase. Cerebral glutamine appeared reduced in fasting MCS pups at 3, 6, and 8 h of age. A considerable disturbance of the adenine nucleotide pool was noted between 3-9 h in MCS pups; while the cerebral energy reserve was diminished in MCS pups between 3-24 h. The data of reduced cerebral energy status and reserve suggest that cerebral energy production was diminished. Although glucose levels were low at 3 h, subsequent recovery was not immediate as adenine-nucleotides remained low beyond the period of hypoglycemia. The combined effects of intrauterine growth retardation and transient neonatal hypoglycemia appear to result in reduced cerebral oxidative metabolism; this occurs despite an apparent enhanced utilization of alternate fuels. (Pediatr Res 20: 662-667,1986 uterine growth retardation is abnormal, and is characterized by fasting hypoglycemia, attenuated FFA levels, and increased plasma levels of gluconeogenic amino acids (3-5). Symptomatic fasting hypoglycemia may have adverse effects on the developing central nervous system (6). Hypoglycemia, combined with the adverse effects of intrauterine growth retardation, may seriously affect fetal brain growth and future brain function. Previous studies in our laboratory among mildly growth retarded newborn dogs demonstrated that the cerebral cortical metabolic state appeared unperturbed in the fetus at the time of birth (7). However, cerebral cortical metabolic changes in growth retarded newborn dogs were most marked with the development of fasting neonatal hypoglycemia after birth. Brain glucose and glycogen content and the calculated energy reserve were diminished during the 24-h period following birth. Nonetheless, cerebral ATP levels were unaltered. Cerebral amino acid patterns suggested that the glutamate group of amino acids were functioning as alternate fuels and were being oxidized to support brain energy metabolism.As 3 days of maternal nutritional deprivation only resulted in a small reduction of fetal growth, we have extended the period of nutritional deprivation to 5 days. This extended period of nutrient withdrawal has resulted in marked intrauterine growth retardation, and has produced circulating substrate perturbations which parallel those observed in the human growth-retarded infant (5). The present report concerns the e...

Carbohydrate and Energy Metabolism in the Brain of Rats With Thromboxane A2-Induced Fetal Growth Restriction

“…They ascribed these findings to the absence of hypoxia at the level required to disrupt oxidative metabolism and the energy state of the brain. Kliegman et al (11) demonstrated using a maternal canine starvation model that cerebral charge in FGR neonates was unaffected, whereas their calculated energy reserve was lower than that of controls. Theoretically, depression of oxygen delivery to respiring tissues increases the ADP to ATP ratio (ADP/ATP).…”

“…Manipulations to induce FGR in animal models included surgical ligation of vessels supplying the uteroplacental unit (12) and maternal starvation (11). However, these models do not necessarily reflect the pathophysiology of FGR.…”

“…Several studies have investigated the mechanisms of brain injuries in FGR model animals (11)(12)(13). Manipulations to induce FGR in animal models included surgical ligation of vessels supplying the uteroplacental unit (12) and maternal starvation (11).…”