Nomogram for 2-Deoxyglucose Lumped Constant for Rat Brain Cortex

The quantitation of local cerebral metabolic rate of glucose with the 2-deoxyglucose technique of Sokoloff requires the use of a correction factor, or lumped constant. We have shown previously (Pardridge et al., 1982) that a simple model may be formulated to predict changes in the lumped constant that occur due to alterations in the distribution of glucose and 2-deoxyglucose in brain. Given experimentally observed values for brain and plasma glucose concentrations, the 2-deoxyglucose lumped constant may be determined from a nomogram constructed from knowledge of the blood–brain barrier transport constants (KM, Vmax, KD) for glucose and for 2-deoxyglucose. However, the nomogram is constructed from transport constants determined in the barbiturate-anesthetized state. The applicability of the nomogram to other physiologic states was examined in the present studies. Large changes in blood–brain barrier hexose transport constants do not appreciably alter the shape of the nomogram, if the changes in KM or Vmax for glucose or for 2-deoxyglucose are the same. Moreover, glucose and 2-deoxyglucose are both transported by the same hexose carrier, and selective changes in the transport of only one hexose have not been reported. Therefore, it is probable that the nomogram constructed from transport constants measured under barbiturate anesthesia is useful in predicting the lumped constant in a variety of physiologic states.

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GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier

Nature Genetics ◽

10.1038/ng0298-188 ◽

1998 ◽

Vol 18 (2) ◽

pp. 188-191 ◽

Cited By ~ 256

Author(s):

Glen Seidner ◽

Marcela Garcia Alvarez ◽

Jih-I Yeh ◽

Kevin R. O'Driscoll ◽

Jörg Klepper ◽

...

Keyword(s):

Blood Brain Barrier ◽

Deficiency Syndrome ◽

Brain Barrier ◽

Glut 1 ◽

Blood Brain ◽

Hexose Carrier

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Endothelin-1 as a Mediator of Endothelial Cell–Pericyte Interactions in Bovine Brain Capillaries

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199704000-00012 ◽

1997 ◽

Vol 17 (4) ◽

pp. 464-469 ◽

Cited By ~ 72

Author(s):

Marie-Pierre Dehouck ◽

Paul Vigne ◽

Gérard Torpier ◽

Jean Philippe Breittmayer ◽

Roméo Cecchelli ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Brain Cortex ◽

Bovine Brain ◽

Brain Barrier ◽

Target Cells ◽

Brain Capillaries ◽

Endothelin 1 ◽

Blood Brain

Endothelial cells and pericytes are closely associated in brain capillaries. Together with astrocytic foot processes, they form the blood–brain barrier. Capillaries were isolated from bovine brain cortex. Pure populations of endothelial cells and pericytes were isolated and cultured in vitro. Polarized monolayers of endothelial cells preferentially secreted immunoreactive endothelin-1 (Et-1) at their abluminal (brain-facing) membrane. They did not express receptors for Et-1. Pericytes expressed BQ-123-sensitive ETA receptors for endothelins as evidenced by 125I-Et-1 binding experiments. These receptors were coupled to phospholipase C as demonstrated by intracellular calcium measurements using indo-1-loaded cells. Addition of Et-1 to pericytes induced marked changes in the cell morphology that were associated with a reorganization of F-actin and intermediate filaments. It is concluded that Et-1 is a paracrine mediator at the bovine blood–brain barrier and that capillary pericytes are target cells for endothelium-derived Et-1.

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Blood-brain barrier permeability of glucose and ketone bodies during short-term starvation in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.6.e1161 ◽

1995 ◽

Vol 268 (6) ◽

pp. E1161-E1166 ◽

Cited By ~ 19

Author(s):

S. G. Hasselbalch ◽

G. M. Knudsen ◽

J. Jakobsen ◽

L. P. Hageman ◽

S. Holm ◽

...

Keyword(s):

Glucose Transport ◽

Blood Brain Barrier ◽

Plasma Glucose ◽

Ketone Bodies ◽

Brain Barrier ◽

Affinity Constant ◽

Indicator Method ◽

Blood Brain ◽

The Brain ◽

Expected Increase

The blood-brain barrier (BBB) permeability for glucose and beta-hydroxybutyrate (beta-OHB) was studied by the intravenous double-indicator method in nine healthy subjects before and after 3.5 days of starvation. In fasting, mean arterial plasma glucose decreased and arterial concentration of beta-OHB increased, whereas cerebral blood flow remained unchanged. The permeability-surface area product for BBB glucose transport from blood to brain (PS1) increased by 55 +/- 31%, whereas no significant change in the permeability from brain back to blood (PS2) was found. PS1 for beta-OHB remained constant during starvation. The expected increase in PS1 due to the lower plasma glucose concentration was calculated to be 22% using previous estimates of maximal transport velocity and Michaelis-Menten affinity constant for glucose transport. The determined increase was thus 33% higher than the expected increase and can only be partially explained by the decrease in plasma glucose. It is concluded that a modest upregulation of glucose transport across the BBB takes place after starvation. Brain transport of beta-OHB did not decrease as expected from the largely increased beta-OHB arterial level. This might be interpreted as an increase in brain transport of beta-OHB, which could be caused by induction mechanisms, but the large nonsaturable component of beta-OHB transport makes such a conclusion difficult. However, beta-OHB blood concentration and beta-OHB influx into the brain increased by > 10 times. This implies that the influx of ketone bodies into the brain is largely determined by the amount of ketones present in the blood, and any condition in which ketonemia occurs will lead to an increased ketone influx.

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Blood–brain barrier integrity is unaltered in human brain cortex with diabetes mellitus

Brain Research ◽

10.1016/s0006-8993(02)03294-8 ◽

2002 ◽

Vol 954 (2) ◽

pp. 311-316 ◽

Cited By ~ 32

Author(s):

Jiapei Dai ◽

Gijs F.J.M Vrensen ◽

Reinier O Schlingemann

Keyword(s):

Diabetes Mellitus ◽

Human Brain ◽

Blood Brain Barrier ◽

Brain Cortex ◽

Brain Barrier ◽

Barrier Integrity ◽

Blood Brain ◽

Blood Brain Barrier Integrity ◽

Human Brain Cortex

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Two-Day Starvation Does Not Alter the Kinetics of Blood-Brain Barrier Transport and Phosphorylation of Glucose in Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1985.6 ◽

1985 ◽

Vol 5 (1) ◽

pp. 40-46 ◽

Cited By ~ 24

Author(s):

Paul D. Crane ◽

William M. Pardridge ◽

Leon D. Braun ◽

William H. Oldendorf

Keyword(s):

Blood Flow ◽

Glucose Metabolism ◽

Blood Brain Barrier ◽

Plasma Glucose ◽

Brain Barrier ◽

Brain Blood Flow ◽

Brain Glucose ◽

Blood Brain ◽

Glucose Phosphorylation ◽

Kinetics Of

The blood-brain barrier (BBB) transport and brain phosphorylation of glucose were assessed in conscious rats subjected to 2 days of starvation. Although plasma glucose decreased, no significant changes in brain blood flow, BBB glucose transport, or 2-deoxy-d-glucose phosphorylation were observed. The data suggest that adaptive changes of brain glucose metabolism previously observed in starvation are located beyond the initial steps of brain entry and phosphorylation.

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Cholinergic Cerebral Vasodilatation in the Rabbit: Absence of Concomitant Metabolic Activation

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1982.24 ◽

1982 ◽

Vol 2 (2) ◽

pp. 241-247 ◽

Cited By ~ 30

Author(s):

Oscar U. Scremin ◽

Ralph R. Sonnenschein ◽

Eduardo H. Rubinstein

Keyword(s):

Blood Flow ◽

Blood Brain Barrier ◽

Cholinesterase Inhibitor ◽

Metabolic Activation ◽

Brain Barrier ◽

Mechanically Ventilated ◽

Cerebral Metabolic Rate ◽

Sagittal Sinus ◽

Blood Brain ◽

Cerebral Vasodilatation

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O–30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects, It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.

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Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y01-046 ◽

2001 ◽

Vol 79 (9) ◽

pp. 793-798 ◽

Cited By ~ 31

Author(s):

Mehmet Kaya ◽

Mutlu Küçük ◽

Rivaze Bulut Kalayci ◽

Vedat Cimen ◽

Candan Gürses ◽

...

Keyword(s):

Magnesium Sulfate ◽

Blood Brain Barrier ◽

Plasma Glucose ◽

Evans Blue ◽

Brain Barrier ◽

Protective Effects ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability

Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05 ± 0.57 vs. 2.58 ± 0.14 mg/dL in the Mg2+ group, and 7.14 ± 0.42 vs. 2.78 ± 0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4 ± 0.66 vs. 118 ± 2.23 mg/dL in the insulin group, and 7 ± 1.59 vs. 118 ± 4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.Key words: blood-brain barrier, hypoglycemia, Mg2+, Evans-blue.

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