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Biomedical subjects

A Gjedde

Publications and source records attributed to A Gjedde.

At least 199 records · Page 11Linked to original sources
PubMed1984

Estimates of Michaelis-Menten constants for the two membranes of the brain endothelium.

Tracer studies on facilitated diffusion across the blood-brain barrier lead to the calculation of Michaelis-Menten constants that describe the rate of transport. However, the barrier consists of two endothelial cell membranes, and the relevance of single Michaelis-Menten constants in relation to the two cell membranes is unknown. We have formulated a model of two endothelial cell membranes and show that the measured Michaelis-Menten constants are simple functions of the properties of the individual membranes when transport across the endothelium is rapid (P1 greater than 10(-6) cm s-1). We also show that the Michaelis-Menten constants determined in tracer experiments describe facilitated diffusion in the steady state only if the two membranes have similar transport properties. As an application of this observation, we have examined three experimental studies that measure glucose transport in the steady state and show that the Michaelis-Menten constants for glucose transport calculated from the tracer experiments are equal to the constants calculated from the steady-state experiments. We conclude that the luminal and abluminal membranes of brain capillary endothelial cells have equal glucose transport properties.

Biological Transport, Active↗
PubMed1984

Blood-brain transfer of galactose in experimental galactosemia, with special reference to the competitive interaction between galactose and glucose.

The interaction between glucose and galactose during transport across the cerebral capillary endothelium was studied in anesthetized rats. Although galactose is present in the diet of suckling mammals and is a potential substrate for brain metabolism in adult mammals, its effect on glucose transport in adult rats is unknown. A kinetic model was formulated to analyze the effect of chronically elevated galactose levels on glucose transport in adult rats. The analysis indicated that galactose and glucose compete for the same transport mechanism in the cerebral capillary endothelium. The Tmax of glucose and galactose were both about 380 mumol 100 g-1 min-1 and the Kt of galactose (30 mM) was about three times that of glucose (10 mM). During prolonged galactosemia in adult rats, neither the Tmax, nor the Kt of either competitor changed substantially when compared with rats subjected to acute galactosemia. At 10 mM galactose in plasma in rats with acute galactosemia, the inhibition of glucose transport, simulated a 25% reduction of plasma glucose, and in rats with chronic galactosemia a 20% reduction. This moderate effect is in contrast to the effect of galactose in suckling rats in which 10 mM galactose in plasma reduced the glucose transport to a level corresponding to a 50% reduction of the plasma glucose concentration.

Animals↗
PubMed1984

The effect of metrizamide on regional brain glucose metabolism in the rat.

The X-ray contrast material metrizamide is structurally related to 2-deoxyglucose and inhibits brain glucose phosphorylation in vitro. In vivo, the present autoradiographic study with labeled 2-deoxyglucose revealed a global reduction of brain glucose phosphorylation after metrizamide administration in the cisterna magna of rats. The reduction averaged 18% of all regions.

Animals↗
PubMed1983

Biochemical modulation of blood-brain barrier permeability.

Hydrophilic substrates necessary for brain function cross the capillary by facilitated diffusion. The facilitation has many features in common with enzyme-catalyzed reactions and is probably subserved by protein entities in the endothelial wall. The proteins act as receptors, recognizing substrate molecules, and as translocators, giving the molecules access to an aqueous path through the endothelium. These receptor-translocators can be saturated, and the transport is subject to competitive inhibition by substrate analogs. Thus, amino acids inhibit the transport of each other, and galactose can inhibit glucose transport in suckling rats. The proteins can be induced, as in the case of ketone transport in starvation, and repressed, as in the case of glucose transport in hyperglycemia. In rats with hyperglycemia for three weeks, the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 mumol/hg/min. An important result of the description is the understanding that rigid distinctions between the function of receptors, translocators, and enzymes is impossible. Understanding of the biochemical properties of facilitated diffusion may help explain a variety of symptoms in many 'inborn errors of metabolism'. This understanding has followed greater, recent insights into the general properties of the blood-brain barrier (45,46,47).

Adaptation, Physiological↗
PubMed1983

Autoradiographic determination of regional brain glucose content.

Brain glucose content is an important experimental variable that affects the value of the "lumped constant" of the 2-deoxyglucose method. The apparent volume of distribution in brain of the nonmetabolizable glucose analog, 3-O-methylglucose, depends only on the glucose content. From the kinetic constants of glucose transport and the apparent volume of distribution, we used autoradiography to calculate the regional glucose content of the normal rat brain. The regional glucose content varied only insignificantly in gray matter regions; the average glucose content of all rat brain slices examined was 4 mumol g-1, with an average plasma glucose concentration of 8.6 mM. Regional values varied between 3.4 and 4.6 mumol g-1. Thus, there is no reason to believe that the regional values of the lumped constant vary significantly in normal rat brains.

Animals↗
PubMed1983

Modulation of substrate transport to the brain.

Variations of substrate transport across the cerebral capillary endothelium were examined in response to variations of the substrate demand of the brain tissue, and to variations of substrate concentration in the blood. The substrates examined included glucose and ketone bodies. The transport changes were measured in rats, using an indicator fractionation method modified by the reviewer. Four mechanisms appeared to contribute to the adjustment of substrate transport to variations in substrate demand. The first and least important mechanism was the change of concentration gradient across the endothelium that occurred when the substrate consumption rate changed. The second mechanism was the flow-dependency of the average capillary substrate concentration: the higher the perfusion rate, the higher the average capillary concentration. This mechanism failed to account for the changes of substrate transport observed during marked increases of the metabolic rate. The third and most important mechanism was a change of the capillary diffusion capacity, probably associated with a change of the number of perfused capillaries. The fourth mechanism, not previously described, was an adaptation of transport to permanent changes of substrate concentration in the blood. This mechanism appeared to reflect changes of the concentration (and affinity?) of transport proteins in the plasma membranes of endothelial cells, possibly in association with changes of cellular protein synthesis and gene expression.

Animals↗
PubMed1982

Hyperglycemic ischemia of rat brain: the effect of post-ischemic insulin on metabolic rate.

To identify the mechanism by which hyperglycemia impairs recovery after cerebral ischemia, cortical blood flow (CBF), cortical metabolic rate for oxygen (CMRO2), and the cortical phosphorylation rate for glucose (CPRg1c) were measured in rats 1 h after a global ischemic insult of the brain. A control group remained hyperglycemic after ischemia. The experimental group received insulin which reduced plasma glucose during the period of recirculation after ischemia. Thus, the brains of both groups were hyperglycemic before and during ischemia. The CMRO2 after ischemia was higher in insulin-treated rats than in hyperglycemic rats (250 vs 168 mumol . 100 g-1 . min-1) while the CPRg1c was lower (22 vs 58 mumol . 100 g-1 . min-1). We conclude that glucose-induced inhibition of oxygen consumption in brain contributes to the impaired recovery after ischemia.

Animals↗
PubMed1982

Persistent oligemia of rat cerebral cortex in the wake of spreading depression.

Cerebral blood flow during and after spreading depression (SD) was studied in rat brain by quantitative autoradiography. The rise of cortical blood flow during SD was followed by 20 to 25% reduction below normal after SD, lasting at least an hour. Blood flow in th putamen, thalamus, and hippocampus did not change at any time during or after SD. Previous measurements of cerebral blood flow in humans showed that migraine attacks may be accompanied by wavelike spreading oligemia (Olesen et al, 1981). We speculate that the spreading oligemia of migraine may be a phenomenon physiologically related to the present finding of an oligemia after SD.

Animals↗
PubMed1982

Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination.

The 2-deoxyglucose (2-DG) method of functional neuroanatomical mapping25 was re-examined in order to (1) obtain physical descriptions of the transfer constants K1 and k2, (2) estimate the changes of the 'lumped constant' with the condition of the experimental animals, and (3) examine the use of 3-O-methylglucose (3-O-MG) to estimate the fraction of unphosphorylated 2-DG in the tissue, and the value of the 'lumped constant'. The transfer constants K1 and k2 were shown to be simple exponential forms of the apparent permeability of the cerebral capillary endothelium to glucose and glucose analogs. The 'lumped constant' was shown to be influenced by any reduction of the ratio between glucose transport and glucose phosphorylation in the tissue, e.g. by hypoglycemia and increased glycolysis, while hyperglycemia and decreased glycolysis resulted in very minor changes of the 'lumped constant'. The glucose analog 3-O-MG was shown accurately to trace unphosphorylated 2-DG in brain and to be an index of the brain content of glucose and the regional value of the 'lumped constant'. In addition, 3-O-MG proved to be an accurate tracer of unphosphorylated 2-DG for experimental times as low as 10 min.

Animals↗
PubMed1982

[Simultaneous diffusion of inositol and mannitol in the rat brain].

The diffusion of both inositol and mannitol has been determined simultaneously by the integral bolus method in rat brain. The permeability constant (Kin) of inositol averaged 0.27 +/- 0.02 ml X (100 g)-1 X min-1 or 4 X 10(-7) cm X s-1 at a cerebral capillary surface area of 100 cm2 x g-1. The permeability of mannitol was 0.08 +/- 0.01 ml X (100 g)-1. min-1 or 1 X 10(-7) cm X s-1. Neither glucose nor galactose affected the inositol permeability. Hypoglycemia increased somewhat the Km value for mannitol. The basal ganglia showed an increase Km for both substrates as compared with those obtained for cortex, temporal and parietal tissues.

Animals↗
PubMed1981

Blood-brain glucose transfer: repression in chronic hyperglycemia.

Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

Animals↗
PubMed1981

High- and low-affinity transport of D-glucose from blood to brain.

Measurements of the unidirectional blood-brain glucose flux in rat were incompatible with a single set of kinetic constants for transendothelial transport. At least two transfer mechanisms were present: a high-affinity, low-capacity system, and a low-affinity, high-capacity system. The low-affinity system did not represent passive diffusion because it distinguished between D- and L-glucose. The Tmax and Km for the high-affinity system were 0.16 mmol 100 g-1 min-1 and 1 mM; for the low-affinity system, approximately 5 mmol 100 g-1 min-1 and approximately 1 M. With these values, physiological glucose concentrations were not sufficient to saturate the low-affinity system. In normoglycemia, therefore, three independent pathways of glucose transport from blood to brain appear to exist: a high-affinity facilitated diffusion pathway of apparent permeability 235 X 10(-7) cm s-1, a specific but nonsaturable diffusion pathway of permeability 85 x 10(-7) cm s-1, and a nonspecific passive diffusion pathway of permeability 2 x 10(-7) cm s-1.

Animals↗
PubMed1981

Blood-brain glucose transfer in spreading depression.

Spreading depression in rat brain cortex is associated with a twofold increase of cerebral blood flow. It is not known whether this increase is coupled to increases of cerebral metabolic rate and glucose transport from blood to brain. During the passage of a single spreading depression, we measured blood-brain glucose transport and glucose metabolism in rat cerebral cortex by single intravenous injection of tracer glucose. Blood flow and tissue content of glucose were measure as well. Reduction of tissue glucose and the consequent increase of net transfer of glucose from blood to brain were consistent with a threefold increase of the consumption of glucose before the increase of blood flow. There was no increase of unidirectional blood-brain transfer.

Animals↗
PubMed1980

Extracellular potassium and blood flow in the post-ischemic rat brain.

The concentration of extracellular potassium, [K+]e, was measured in parietal cortex and basal ganglia of rats during and after ten minutes of complete cerebral ischemia. The post-ischemic normalization of [K+]e was considerably delayed in parietal cortex compared to basal ganglia, but in both regions, [K+]e reached its normal concentration within 4 min of the end of the ischemia. Also, in both regions blood flow was elevated at the time of maximal [K+]e decrease. Our findings suggest that the normalization of [K+]e and cerebrovascular resistance after ischemia are related by positive feed-back, possibly via the stimulation of Na+-K+-ATPase.

Animals↗