DEVELOPMENTAL MODULATION OF BLOOD-BRAIN-BARRIER GLUCOSE-TRANSPORT IN THE RABBIT

Blood-brain barrier (BBB) glucose transport rates were measured using the intracarotid injection method in newborn, 14-day-old suckling, 28- day-old weanling and adult rabbits, and compared with membrane transpo rter density. Light microscope immunochemistry confirmed the presence of the GLUT1 glucose transporter isoform in these rabbits. Quantitativ e electron microscopic immunogold analyses of GLUT1-immunoreactive sit es per micrometer of capillary membrane indicated GLUT1 density increa sed with age, and correlated with in vivo measurements of V-max. Maxim al transport velocities (V-max) of glucose transfer (an indicator of t he activity and relative number of transporter proteins) increased sig nificantly (P = 0.05) with age: in neonates V-max = 0.61 mu mol.min(-1 ).g(-1), in sucklings V-max = 0.68 mu mol.min(-1).g(-1), in weanlings V-max = 0.88 mu mol.min(-1).g(-1), and in adults Vmax = 1.01 mu mol.mi n(-1) g(-1). Cerebral blood flow (CBF) rates, increased with age from 0.19 and 0.26 ml.min(-1).g(-1) in neonates and sucklings to 0.51 (wean lings) and 0.70 (adults) ml.min(-1).g(-1). Non-linear regression analy ses indicated the half-saturation constant (K-m) for glucose transport ranged from 13 mM in adult rabbits to 19 mM in 14-day-old sucklings: differences in K-m were not significant. Age-related changes in the Pe rmeability-Surface Area product (PS +/-S.E.) of both water and glucose were also seen. At all ages studied, the diffusion component (K-d) of glucose uptake was not distinguishable from zero. We conclude develop mental up-regulation of the rabbit BBB glucose transporter is characte rized by no changes in transporter affinity, and provide the first dem onstration of increased membrane transporter proteins correlating with an age-related increase (65%) in glucose transporter maximal velocity .