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 (B BB) GLUT1 glucose transporter. The expression of the BBB-GLUT1 gene is augm ented in brain endothelial cultured cells incubated with brain-derived trop hic factors and the brain-derived peptide preparation Cerebrolysin (Cl, EBE WE, Austria). The aim of the present investigation was to determine if Cl i nduces similar changes in the expression of the BBB-GLUT1 gene following it s administration to rats in vivo. The BBB glucose transporter activity was investigated with the intracarotid artery perfusion technique using [H-3]di azepam as cerebral blood flow marker. The acute or chronic administration o f Cl markedly increased the brain permeability surface area of D-[C-14]gluc ose 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 g lucose transporter was correlated with a significant rise in the abundance of the BBB-GLUT1 protein measured by both Western blot analysis and immunoc ytochemistry, and with a decrease in the transcript levels of this transpor ter. Data presented here demonstrate that the in vivo administration of Cl increases the transport of glucose from blood to brain via BBB-GLUT1 gene e xpression. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.