GLUT1 GLUCOSE-TRANSPORTER ACTIVITY IN HUMAN BRAIN INJURY

The principal glucose transporter at the blood-brain barrier (BBB) is the Glut1 isoform, and transporter density is believed to be an index of cerebral metabolic rate. In the present study, glucose transporter expression was studied in tissue resected 7-8 h after acute traumatic brain injuries in 2 patients. Light microscopic immunochemistry indica ted a zone of complete loss of the Glut1 glucose transporter isoform i n microvessel endothelial cells adjacent to sites of small vessel inju ry, concentrically surrounded by a narrow zone of variable Glut1, and distally surrounded by capillaries with typically immunoreactive endot helia in nondisrupted parenchyma. Variably reactive capillaries displa yed alternating sectors of greatly reduced and highly reactive Glut1 d ensity, suggesting a high density and low density of transporter activ ity in contiguous endothelial cells. Quantitative electron microscopic immunogold analyses demonstrated that the transporter was predominant ly localized to the luminal and abluminal endothelial membranes, with lesser reactivity in cytoplasm; pericyte Glut1 was minimally above bac kground levels. In endothelial sectors with reduced Glut1 transporter immunoreactivity, the luminal:abluminal ratio of Glut1 epitopes was le ss than unity; while it is greater than unity in highly reactive endot helial cells. The number of Glut1-immunoreactive sites per micrometer of capillary membrane was not signficantly different from previous rep orted Glut1 density in seizure resections, and about 2- to 3-fold high er than in human red cells. In the same tissue samples, qualitative im munogold electron microscopy of human serum albumin indicated leakage of this protein (MW 65,000) from the vascular space into pericapillary regions. Thus the high Glut1 density observed in capillaries from acu tely injured brain occurs concomitantly with compromised barrier funct ion.