Mechanisms of glucose transport at the blood-brain barrier: an in vitro study

How the brain meets its continuous high metabolic demand in light of varyin g plasma glucose levels and a functional blood-brain barrier (BBB) is poorl y understood. GLUT-1, found in high density at the BBB appears to maintain the continuous shuttling of glucose across the blood-brain barrier irrespec tive of the plasma concentration. We examined the process of glucose transp ort across a quasi-physiological in vitro blood-brain barrier model. Radiol abeled tracer permeability studies revealed a concentration ratio of ablumi nal to luminal glucose in this blood-brain barrier model of approximately 0 .85. Under conditions where [glucose](lumen) was higher than [glucose](ablu men), influx of radiolabeled 2-deoxyglucose from lumen to the abluminal com partment was approximately 35% higher than efflux from the abluminal side t o the lumen. However, when compartmental [glucose] were maintained equal, a reversal of this trend was seen (approximately 19% higher efflux towards t he lumen), favoring establishment of a luminal to abluminal concentration g radient. Immunocytochemical experiments revealed that in addition to segreg ation of GLUT-1 (luminal > abluminal), the intracellular enzyme hexokinase was also asymmetrically distributed (abluminal > luminal). We conclude that glucose transport at the CNS/blood interface appears to be dependent on an d regulated by a serial chain of membrane-bound and intracellular transport ers and enzymes. (C) 2001 Published by Elsevier Science B.V.