INTERICTAL SEIZURE RESECTIONS SHOW 2 CONFIGURATIONS OF ENDOTHELIAL GLUT1 GLUCOSE-TRANSPORTER IN THE HUMAN BLOOD-BRAIN-BARRIER

Immunogold electron microscopy was used to analyze and quantify the Gl ut1 glucose transporter in brain tissue from five patients undergoing surgery for treatment of seizures. Samples were prepared from two diff erent regions of each resection: (1) the most actively spiking epilept ogenic site, and (2) the least actively spiking region, as indicated b y intraoperative EEG monitoring. Two configurations of endothelial cel l Glut1 were observed. About one half of the capillary profiles examin ed displayed abundant Glut1 immunoreactivity on both luminal and ablum inal endothelial membranes In the remainder of the profiles, reduced G lut1 labeling was seen, but adjacent erythrocyte membranes remained hi ghly Glut1 immunoreactive, suggesting that reduced endothelial Glut1 r eactivity uas not attributable to method artifacts. Immunogold studies using antisera to human glial fibrillary acidic protein and human ser um albumin demonstrated increased quantities of these two epitopes in the extravascular regions in which more EEG spiking activity had been demonstrated. These observations were consistent with the hypotheses t hat capillary integrity was more compromised, and gliosis was quantita tively increased, in the more actively spiking region of the resection . Altered glucose transporter activity in the blood-brain barrier was characterized by a bimodal Glut1 distribution in which the smaller (ty pe B) endothelial cells displayed low Glut1 immunoreactivity, whereas adjacent (and even contiguous) larger (type A) endothelial cells showe d 5- to 10-fold greater expression of membrane Glut1 transporter prote in. Because this transporter facilitates glucose entry to the brain, s mall pericapillary volumes of brain tissue may have quite different co ncentrations of glucose. We hypothesize that in complex partial seizur es and other forms of brain insult, an alteration of blood-brain barri er Glut1 glucose transporter activity is indicated by the appearance o f these two subpopulations of endothelial cells. In comparison with pr evious studies of human brain capillaries in hemangioblastoma and brai n injury, endothelial Glut1 density was apparently reduced (interictal ly) in affected temporal lobes of patients with complex partial seizur es.