Transient rise of glucose uptake in the fetal rat brain after brief episodes of intrauterine ischemia

Abstract

In a rat model of intrauterine growth retardation and fetal brain ischemia, the maternal-fetal circulation was obstructed for up to 40 min in 20-day gestational age rats by occluding (restriction) the uterine blood vessels supplying the placenta. After restriction, flow was returned (reperfusion) for designated times. A time-dependent depletion of cerebral pyruvate levels (from 0.2 +/- 0.02 to 0.06 +/- 0.01 mumol/g wet weight) accompanied by an elevation in lactate concentration (from 1.95 +/- 0.03 to 7.00 +/- 0.56 mumol/g wet weight) was observed after 20 min restriction. During 20 min, reperfusion lactate levels continued to increase, then gradually decreased as the reperfusion continued for approximately 2 h. A drastic increase in the lactate/pyruvate ratio (from 10 to 117) suggested that the fetal brain was relying on anaerobic glycolysis to meet its energy demands. In addition, a time-dependent decrease in fetal brain phosphocreatine (PCr) content from 2.54 +/- 0.26 to 1.52 +/- 0.15 mM was observed after 20 min of maternal-fetal blood flow obstruction. ATP levels gradually decreased after 20 min restriction from 1.62 +/- 0.13 to 0.59 +/- 0.09 mM. After 30 min reperfusion ATP, PCr and pyruvate returned to their normal values. These metabolic changes observed are concordant with the ability of the ischemic fetal brain to sustain adequate levels of ATP for energy-requiring cellular processes. The capacity of glucose transporters to facilitate transport of glucose into brain tissue was assessed ex vivo, using [3H]2-deoxyglucose (2D-Glu).(ABSTRACT TRUNCATED AT 250 WORDS)