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 indicated a zone of complete loss of the Glut1 glucose transporter isoform in microvessel endothelial cells adjacent to sites of small vessel injury, concentrically surrounded by a narrow zone of variable Glut1, and distally surrounded by capillaries with typically immunoreactive endothelia in nondisrupted parenchyma. Variably reactive capillaries displayed alternating sectors of greatly reduced and highly reactive Glut1 density, suggesting a high density and low density of transporter activity in contiguous endothelial cells. Quantitative electron microscopic immunogold analyses demonstrated that the transporter was predominantly localized to the luminal and abluminal endothelial membranes, with lesser reactivity in cytoplasm; pericyte Glut1 was minimally above background levels. In endothelial sectors with reduced Glut1 transporter immunoreactivity, the luminal:abluminal ratio of Glut1 epitòpes was less than unity; while it is greater than unity in highly reactive endothelial cells. The number of Glut1-immunoreactive sites per micrometer of capillary membrane was not significantly different from previous reported Glut1 density in seizure resections, and about 2- to 3-fold higher than in human red cells. In the same tissue samples, qualitative immunogold 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 acutely injured brain occurs concomitantly with compromised barrier function.
Department of Neurology, UCLA School of Medicine 90095, USA.
E M
EM
Cornford
S
S
Hyman
M E
ME
Cornford
M J
MJ
Caron
D000063:Accidents, Traffic; D000293:Adolescent; D001812:Blood-Brain Barrier / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000502:physiology; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D014948:Wounds, Gunshot / Q000378:metabolism / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human