THE HUMAN BRAIN GLUT1 GLUCOSE-TRANSPORTER - ULTRASTRUCTURAL-LOCALIZATION TO THE BLOOD-BRAIN-BARRIER ENDOTHELIA

Immunogold electron microscopy was used to examine human brain resecti ons to localize the GLUT1 glucose transporter. The tissue examined was obtained from a patient undergoing surgery for treatment of seizures, and the capillary profiles examined had characteristics identical to those described previously for active, epileptogenic sites (confirmed by EEG analyses). A rabbit polyclonal antiserum to the full-length hum an erythrocyte glucose transporter (GLUT1) was labeled with 10nm gold particle-secondary antibody conjugates and localized immunoreactive GL UT1 molecules in human brain capillary endothelia, with <0.25% of the particles beyond the capillary profile. Erythrocyte membranes were als o highly immunoreactive, whereas macrophage membranes were GLUT1-negat ive. The number of immunoreactive sites per capillary profile was obse rved to be 10-fold greater in humans than in previous studies of rat a nd rabbit brain capillaries. In addition, half of the total number of immunoreactive gold particles were localized to the luminal capillary membrane. We suggest that the blood-brain barrier GLUT1 glucose transp orter is upregulated in seizures, and this elevated transporter activi ty is characterized by increased GLUT1 transporters, particularly on t he luminal capillary membranes. In addition, acute modulation of gluco se transporter activity is presumed to involve translocation of GLUT1 from cytoplasmic to luminal membrane sites, demonstrable with quantita tive immunogold electron microscopy.