TRANSIENT RISE OF GLUCOSE-UPTAKE IN THE FETAL-RAT BRAIN AFTER BRIEF EPISODES OF INTRAUTERINE ISCHEMIA

In a rat model of intrauterine growth retardation and fetal brain isch emia, the maternal-fetal circulation was obstructed for up to 40 min i n 20-day gestational age rats by occluding (restriction) the uterine b lood vessels supplying the placenta. After restriction, flow was retur ned (reperfusion) for designated times. A time-dependent depletion of cerebral pyruvate levels (from 0.2 +/- 0.02 to 0.06 +/- 0.01 mu mol/g wet weight) accompanied by an elevation in lactate concentration (from 1.95 +/- 0.03 to 7.00 +/- 0.56 mu mol/g wet weight) was observed afte r 20 min restriction. During 20 min, reperfusion lactate levels contin ued to increase, then gradually decreased as the reperfusion continued for approximately 2 h. A drastic increase in the lactate/pyruvate rat io (from 10 to 117) suggested that the fetal brain was relying on anae robic glycolysis to meet its energy demands. In addition, a time-depen dent 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-feta l 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 reper fusion ATP, PCr and pyruvate returned to their normal values. These me tabolic changes observed are concordant with the ability of the ischem ic 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 [H -3]2-deoxyglucose (2D-Glu). A statistically significant increase of 2D -Glu uptake, from 48.9 +/- 2.3 to 69.5 +/- 4.5 pmol/mg (42%) was notic ed in fetal brains after 20 min restriction. Kinetic analysis revealed a 2.2-fold increase in the maximal uptake of [H-3]-2D-Glu after 20 mi n blood flow restriction. Facilitation of specific glucose transporter s triggered by oxygen depletion and glucose reduction, may contribute to the partial resistance of the fetal brain to ischemia and account f or the moderate decrease in ATP energy levels.