In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides

Glucose is the critical metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The expression of the BBB-GLUT1 gene is augmented in brain endothelial cultured cells incubated with brain-derived trophic factors and the brain-derived peptide preparation Cerebrolysin (Cl, EBEWE, Austria). The aim of the present investigation was to determine if Cl induces similar changes in the expression of the BBB-GLUT1 gene following its administration to rats in vivo. The BBB glucose transporter activity was investigated with the intracarotid artery perfusion technique using [H-3]diazepam as cerebral blood flow marker. The acute or chronic administration of Cl markedly increased the brain permeability surface area of D-[C-14]glucose compared to controls (D-[C-14]glucosel[H-3]diazepam ratio, 1.6- to 1.9-fold increase in frontal cortex, P < 0.05). Increased activity of the BBB glucose transporter was correlated with a significant rise in the abundance of the BBB-GLUT1 protein measured by both Western blot analysis and immunocytochemistry, and with a decrease in the transcript levels of this transporter. Data presented here demonstrate that the in vivo administration of Cl increases the transport of glucose from blood to brain via BBB-GLUT1 gene expression. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.