scholarly journals Regional Congruence and Divergence of Glucose Transporters (GLUT1) and Capillaries in Rat Brains

1995 ◽  
Vol 15 (4) ◽  
pp. 681-686 ◽  
Author(s):  
Sylvia Rahner-Welsch ◽  
Johannes Vogel ◽  
Wolfgang Kuschinsky
Keyword(s):  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Subcommissural Organ ◽  
Glucose Transporters ◽  
Brain Structures ◽  
Circumventricular Organs ◽  
Brain Barrier ◽  
Ependymal Cells ◽  
Brain Capillaries ◽  
Blood Brain

The association of glucose transporters (GLUT1) and brain capillaries was tested in different brain structures of rats by a direct comparison of the topologies of capillaries and GLUT1 in identical brain sections. Antibody staining of capillaries (fibronectin) and GLUT1 were made visible by fluorescence microscopy. The results showed differences between brain structures containing a tight and a leaky blood–brain barrier. All capillaries of brain structures with a tight blood–brain barrier showed congruent staining of GLUT1 and capillary morphology. The circumventricular organs that are known to have leaky barrier capillaries were stained by fibronectin antibodies but not by GLUT1 antibodies. Ependymal cells showed moderate staining by GLUT1 antibodies both in areas with tight and leaky barriers. The subcommissural organ appeared to be unique showing neither capillary nor GLUT1 stain. It is concluded that glucose transporters (GLUT1) exist in all brain capillaries of blood–brain barrier structures, whereas they are absent in leaky barrier structures. Moderate amounts of glucose transporter (GLUT1) can also be detected in ependymal cells.

Changes in the glucose transporter of brain capillaries

1992 ◽  
Vol 70 (S1) ◽  
pp. S113-S117 ◽  
Author(s):  
Sami I. Harik
Keyword(s):  
Alzheimer Disease ◽  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Brain Barrier ◽  
Capillary Endothelium ◽  
Brain Capillaries ◽  
Glut 1 ◽  
Blood Brain ◽  
The Brain

Brain capillary endothelium has a high density of the GLUT-1 facilitative glucose transporter protein. This is reasonable in view of the brain's high metabolic rate for glucose and its isolation behind unique capillaries with blood – brain barrier properties. Thus, the brain endothelium, which constitutes less than 0.1% of the brain weight, has to transport glucose for the much larger mass of surrounding neurons and glia. I describe here the changes that occur in the density of glucose transporters in brain capillaries of subjects with Alzheimer disease, where there is a decreased cerebral metabolic rate for glucose, and in a novel clinical entity characterized by defective glucose transport at the blood – brain barrier. In subjects with Alzheimer disease, cerebral microvessels showed a marked decrease in the density of the glucose transporter when compared with age-matched controls, but there was no change in the density of glucose transporters in erythrocyte membranes. Thus, I believe that the decreased density of glucose transporters in the brains of subjects with Alzheimer disease is the result rather than the cause of the disease. In contradistinction, the primary defect in glucose transport at the blood – brain barrier in subjects with the recently described entity is associated with decreased density of GLUT-1 in erythrocyte membranes.Key words: brain microvessels, capillary endothelium, blood – brain barrier, glucose transporter, Alzheimer disease, hypoglycorrhachia.

scholarly journals 17-β-Estradiol: A Powerful Modulator of Blood–Brain Barrier BCRP Activity

2010 ◽  
Vol 30 (10) ◽  
pp. 1742-1755 ◽  
Author(s):  
Anika MS Hartz ◽  
Anne Mahringer ◽  
David S Miller ◽  
Björn Bauer
Keyword(s):  
Blood Brain Barrier ◽  
Ex Vivo ◽  
Brain Barrier ◽  
Cancer Resistance ◽  
Transport Activity ◽  
Brain Capillaries ◽  
Therapeutic Drugs ◽  
Blood Brain ◽  
Capillary Membranes ◽  
Blood Brain Barrier Model

The ATP-driven efflux transporter, breast cancer resistance protein (BCRP), handles many therapeutic drugs, including chemotherapeutics, limiting their ability to cross the blood–brain barrier. This study provides new insight into rapid, nongenomic regulation of BCRP transport activity at the blood–brain barrier. Using isolated brain capillaries from rats and mice as an ex vivo blood–brain barrier model, we show that BCRP protein is highly expressed in brain capillary membranes and functionally active in intact capillaries. We show that nanomolar concentrations of 17-β-estradiol (E2) rapidly reduced BCRP transport activity in the brain capillaries. This E2-mediated effect occurred within minutes and did not involve transcription, translation, or proteasomal degradation, indicating a nongenomic mechanism. Removing E2 after 1 h fully reversed the loss of BCRP activity. Experiments using agonists and antagonists for estrogen receptor (ER)α and ERβ and brain capillaries from ERα and ERβ knockout mice demonstrated that E2 could signal through either receptor to reduce BCRP transport function. We speculate that this nongenomic E2-signaling pathway could potentially be used for targeting BCRP at the blood–brain barrier, in brain tumors, and in brain tumor stem cells to improve chemotherapy of the central nervous system.

Glucose transport by isolated plasma membranes of the bovine blood-brain barrier

1997 ◽  
Vol 272 (5) ◽  
pp. C1552-C1557 ◽  
Author(s):  
W. J. Lee ◽  
D. R. Peterson ◽  
E. J. Sukowski ◽  
R. A. Hawkins
Keyword(s):  
Glucose Transport ◽  
Blood Brain Barrier ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Extracellular Fluid ◽  
Brain Barrier ◽  
Maximal Velocity ◽  
Plasma Membrane Vesicles ◽  
Cerebral Microvessels ◽  
Blood Brain

Luminal and abluminal endothelial plasma membrane vesicles were isolated from bovine cerebral microvessels, the site of the blood-brain barrier. Glucose transport across each membrane was measured using a rapid-filtration technique. Glucose transport into luminal vesicles occurred by a stereospecific energy-independent transporter [Michaelis-Menten constant (K(m)) = 10.3 +/- 2.8 (SE) mM and maximal velocity (Vmax) = 8.6 +/- 2.0 nmol.mg protein(-1).min-1]. Kinetic analysis of abluminal vesicles also showed a transport system with characteristics similar to the luminal transporter (K(m) = 12.5 +/- 2.3 mM and Vmax = 10.0 +/- 1.0 nmol.mg protein-1.min-1). These functional, facilitative glucose transporters were symmetrically distributed between the luminal and abluminal membrane domains, providing a mechanism for glucose movement between blood and brain. The studies also revealed a Na-dependent transporter on the abluminal membrane with a higher affinity and lower capacity than the facilitative transporters (K(m) = 130 +/- 20 microM and Vmax = 1.59 +/- 0.44 nmol.mg protein-1.min-1. The abluminal Na-dependent glucose transporter is in a position to transport glucose from the brain extracellular fluid into the endothelial cells of the blood-brain barrier. The functional significance of its presence there remains to be determined.

Glucose Transporter of the Blood-Brain Barrier and Brain in Chronic Hyperglycemia

1988 ◽  
Vol 51 (6) ◽  
pp. 1930-1934 ◽  
Author(s):  
Sami I. Harik ◽  
Stephen A. Gravina ◽  
Rajesh N. Kalaria
Keyword(s):  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Brain Barrier ◽  
Chronic Hyperglycemia ◽  
Blood Brain

scholarly journals Blood-Brain Barrier Transport and Brain Metabolism of Glucose during Acute Hyperglycemia in Humans1

2001 ◽  
Vol 86 (5) ◽  
pp. 1986-1990
Author(s):  
Steen G. Hasselbalch ◽  
Gitte M. Knudsen ◽  
Brunella Capaldo ◽  
Alfredo Postiglione ◽  
Olaf B. Paulson
Keyword(s):  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Human Subjects ◽  
Brain Barrier ◽  
Indicator Method ◽  
Acute Hyperglycemia ◽  
Blood Brain ◽  
18F Fluorodeoxyglucose ◽  
Positron Emission ◽  
Area Product

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMRglc) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and[ 18F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 ± 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 ± 0.008 vs. 0.059 ± 0.031 mL/100 g·min). The unidirectional clearance of[ 18F]fluorodeoxyglucose (K1*) was reduced from 0.108 ± 0.011 to 0.061 ± 0.005 mL/100 g·min (P < 0.0004). During hyperglycemia, global CMRglc remained constant (21.4 ± 1.2 vs. 23.1 ± 2.2 μmol/100 g·min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMRglc, no regional difference in CMRglc was found. Likewise, CBF remained unchanged. The reduction in K1* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMRglc.

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