Mapping cerebral activity with deoxyglucose.
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Animals↗
Biomedical subjects
L Sokoloff
Publications and source records attributed to L Sokoloff.
Influence of dopaminergic systems on the lateral habenular nucleus of the rat.
The alterations in glucose utilization in the lateral habenular nucleus following the systemic administration of a putative dopaminergic agonist and antagonist have been examined in 48 rats by means of the autoradiographic 2-deoxyglucose technique. The administration of apomorphine (0.15--5 mg/kg) resulted in significant dose-dependent reductions (by 25 +/- 5% following 0.5 mg/kg) in glucose utilization in the lateral habenula. Haloperidol administration (0.01--10 mg/kg) was associated with increased (by 46 +/- 17% with 0.1 mg/kg) glucose utilization in the lateral habenula. The effects of apomorphine upon metabolic activity in the lateral habenula can be prevented by the prior administration of haloperidol (0.1 mg/kg). These observations provide evidence that metabolic activity in the lateral habenula, a nucleus occupying a strategic position between the forebrain and the mesencephalon, may be regulated by the activity in dopaminergic systems.
Animals↗
Retina-dependent activation by apomorphine of metabolic activity in the superficial layer of the superior colliculus.
Studies of the effect of the dopamine agonist apomorphine on local cerebral glucose utilization by means of the carbon-14-labeled deoxyglucose method demonstrate a dose-dependent metabolic activation in the superficial layer of the superior colliculus in the rat. Apomorphine stimulated glucose utilization in a number of other cerebral structures, but only the effect in the superficial layer of the superior colliculus depended on an intact retinal input. This effect was present with the animal in the light or in the dark, but was abolished by enucleation, which left the effects in other cerebral structures unimpaired. Activation of the superificial layer of the superior colliculus appears, therefore, to be secondary to an action of apomorphine on dopaminergic systems within the retina.
Animals↗
Computerized densitometry and color coding of [14C] deoxyglucose autoradiographs.
A computerized image processing system has been developed for quantitative analyses of autoradiographs obtained with the [14C]deoxyglucose method. The system is composed of standard, commercially available components and includes a scanning microdensitometer, computer, image memory and display system, and monochrome and color monitors. The associated computer programs are written in PASCAL. Autoradiographs are automatically scanned, and the optical density of each spot is digitized at a maximum resolution of 65,536 readings per 6.4 x 6.4 mm area and stored in memory. Images can be reconstructed from the data in memory, displayed on the monitors, and utilized for microdensitometric analyses or manipulated for image enhancement, enlargement, or weighted averaging of selected regions. The digitized data can also be utilized to solve the operational equation of the [14C]deoxyglucose method, and color-coded images of autoradiographs can be reconstructed so that each color represents a narrow range of the rate of glucose utilization. By means of this system, it is possible to generate quantitative metabolic maps that display the distribution of actual rates of local glucose utilization throughout the entire central nervous system in regions as small as 100 micrometers or less.
Animals↗
Effect of platelet lysate on growth and sulfated glycosaminoglycan synthesis in articular chondrocyte cultures.
Human platelet lysate (PL) has a strong growth promoting action on rabbit articular chondrocytes in monolayer culture. The responsible factor is heat stable (56 degrees C, 30 minutes) and above 10,000 MW. PL (80 microgram protein/ml) reduces cell protein content and sulfated glycosaminoglycan synthesis. Synthesis of DNA is stimulated within the first 12 hours of culture but the decline in radiosulfate incorporation lags. PL acts to a slight extent on chondrocytes in serum-free media, but its effect is potentiated by "platelet-poor human serum" or fetal bovine serum. PL is one of several agents having such effects on chondrocytes cultured in serum-containing media. Stimulation of growth in this cell type thus reduces nonreplicative biosynthetic activity nonspecifically. In the epiphyseal growth plate and in pathologic alterations of permeability of the matrix of articular cartilage, platelet-derived factors, together with somatomedin or other cofactors in serum, may be the principal mediator of growth of chondrocytes in vivo.
Animals↗
A computer-assisted image-processing system for the analysis of autoradiographs of cerebral metabolic activity.
A computerized image-processing system has been developed for quantitative analyses of the autoradiographs obtained with the [14C]deoxyglucose method. By means of this system, these cerebral metabolic images can be digitized and the resultant data can be manipulated for image construction, enhancement, enlargement, and microdensitometric analysis. It is also possible to generate quantitative color-coded metabolic maps that display the distribution of the actual rates of local glucose utilization throughout the entire central nervous system with a resolution conservatively estimated to be equivalent to that of a full-width-half-maximum of approximately 100 micron.
Animals↗
Effects of ageing on local rates of cerebral glucose utilization in the rat.
The effects of ageing on local rates of glucose utilization in 47 brain structures in resting conscious rats have been examined. Three age groups have been studied: young adult (4 to 6 months), middle-aged (14 to 16 months), and aged (26 to 36 months). The results show that ageing per se is associated with decreases in rates of glucose utilization in specific brain regions. The decreases were not progressive with age, probably because of the influence of a survival effect. Age-related pathological changes are known to occur in some of the brain structures in which decreases in rates of glucose utilization were found. Selective decreases were also found in the caudate-putamen, the parietal cortex and in structures associated with vision and audition. In these latter structures the changes may reflect reductions in local functional activity, perhaps due to decreased sensory input from the primary sensory organs.
Aging↗
Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity.
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Animals↗
Measurement of free glucose turnover in brain.
A method has been developed for the measurement of the turnover rate constant or the half-life of the free glucose content of brain. It is based on an equation derived by the mathematical analysis of a kinetic model of the equilibration of the specific activity of the free glucose in brain with that of the plasma during an infusion of radioactive glucose. The method requires the measurement of the time course of the specific activity of glucose in the arterial plasma during an intravenous infusion of radioactive glucose for a period of 1 to 4 min and the specific activity of the free glucose in brain at the termination of the infusion. The turnover rate constant, or the half-life, is then calculated from these data by means of the operational equation of the method. The technique has been applied to conscious and anesthetized rats. In conscious rats the half-life of the free glucose content of brain was found to be 1.6 +/- 0.5 min (mean +/- S.D.) when the animals were killed by decapitation and 1.2 +/- 0.2 min (mean +/- S.D.) when they were killed by microwave irradiation; this difference is not statistically significant. In anesthetized rats, the half-life was found to be 2.6 +/- 0.8 min (mean +/- S.D.) in those killed by decapitation and 1.8 +/- 0.3 min (mean +/- S.D.) in those killed by microwave irradiation; this difference is statistically significant. The half-life of the glucose content of brain was found to be significantly prolonged during anesthesia and to be significantly and positively correlated with the plasma glucose concentration (r = 0.78; p < 0.001).
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Regional cerebral glucose utilization measured with the 2--[ 14C] deoxyglucose technique: its use in mapping functional activity in the nervous system.
The results of studies with the [ 14C] deoxyglucose technique unequivocally establish that functional activity in specific components of the central nervous system is, as in other tissues, closely coupled to the local rate of energy metabolism. Stimulation of functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. These changes are so profound that they can be visualized directly in autoradiographic representations of local tissue concentrations of [ 14C] deoxyglucose-6-phosphate. Indeed, the existence of such evoked metabolic responses to experimentally induced alterations in local functional activity, together with the ability to visualize them by the [ 14C] deoxyglucose method, has become the basis of a potent technique for the mapping of functional pathways in the central nervous system (Kennedy et al., 1975, 1976; Plum et al., 1976).
Anesthesia, General↗
Metabolic mapping of neural pathways involved in gastrosecretory response to insulin hypoglycaemia in the rat.
1. The central nervous structures involved in the gastrosecretory effect of insulin hypoglycaemia were investigated in twenty urethane-anaesthetized rats, previously provided with a chronic gastric fistula, by means of the 2-deoxy-D-[(14)C]glucose autoradiographic technique.2. Gastric secretion increased in animals in which plasma glucose concentration was reduced to a range of 84-133 mg/100 ml. (mean +/- S.E. of mean, 94 +/- 3) as compared to a range of 125-215 mg/100 ml. (mean +/- S.E. of mean, 162 +/- 8) in animals with normal gastric secretion.3. In fourteen of nineteen structures examined the rate of glucose utilization remained constant over the range of plasma glucose concentrations of 84-215 mg/100 ml. These structures included the ventromedial nucleus of the hypothalamus, the mamillary nuclei, the medial geniculate nuclei, globus pallidus, zona incerta, nucleus ambiguus, supraoptic nucleus, paraventricular nucleus, medial nucleus of the solitary tract, dorsal tegmental nucleus, red nucleus, inferior olivary nucleus, hippocampus and amygdaloid complex.4. A significant inverse correlation between plasma glucose concentration and the rate of glucose consumption was found in the lateral nucleus of the solitary tract, dorsal nucleus of the vagus, perifornical area where fibres of the medial forebrain bundle course, the superior olivary nucleus and the interstitial nucleus of the stria terminalis.5. Except for the superior olivary nucleus and the interstitial nucleus of the stria terminalis, all the structures affected by low plasma glucose concentration have previously been shown to participate in the gastrosecretory response to blockade of glucose utilization by pharmacological doses of 2-deoxy-D-glucose, indicating that these same nuclei are also activated by hypoglycaemia.
Animals↗
The effect of serum on monolayer cell culture of mammalian articular chondrocytes.
Large variations were found in the ability of six species of sera to support growth of rabbit, human and dog articular chondrocytes in monolayer culture. In most instances the DNA content of the cell pellets increased directly as the serum concentration rose from 10 to 30%. Indications of inhibitory as well as growth-promoting actions were found in some sera. Stimulation of rabbit chondrocyte proliferation by increasing concentrations of serum was accompanied by a reduction of radiosulfate incorporation and cell protein content. There was no consistent relation between the response of chondrocytes from a given species and its homologous serum. However, the growth of human chondrocytes was greatly potentiated by human serum provided that interference with initial attachment of the cells to the culture flask by homologous serum was overcome by priming with fetal calf serum.
Animals↗
Local metabolic responses in brain accompanying motor activity.
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Animals↗
Focal seizures inhibit brain protein synthesis.
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Animals↗
Local cerebral energy metabolism: its relationship to local functional activity and blood flow.
The results of studies with the (14C)deoxyglucose technique unequivocally establish that local energy metabolism in cerebral tissues is, as in other tissues, closely coupled to local functional activity. Stimulation of local functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. Local cerebral blood flow is normally distributed among the cerebral structures in almost exact proportion to their rates of glucose utilization and changes together with local glucose consumption in response to altered local functional activity. These results demonstrate that the level of functional activity in the structural and functional components of the central nervous syetem regulates the local rate of energy metabolism, and local blood flow is adjusted to the local metabolic demand.
Animals↗
Specific distribution of metabolic alterations in cerebral cortex following apomorphine administration.
The topographic distribution of dopaminergic receptors in the cerebral cortex closely parallels that of the dopaminergic innervation. In the rat, dopaminergic axons which originate in the mesencephalon are confined to a few discrete regions of the neocortex--anterior cingulate cortex, entorhinal cortex, frontal cortex (particularly anteromedial and supragenual areas) and the transitional zone between the neocortex and the pyriform cortex. Moreover, biochemical examinations of processes generally considered to be indicative of dopaminergic neuro-transmission--neuronal uptake of labelled dopamine or dopamine-activation of adenylate cyclase activity--have confirmed a highly restricted locus of action of dopaminergic systems in the cerebral cortex. We describe here data obtained using the 2-deoxyglucose technique in conjunction with conventional neuropharmacological techniques, suggesting that the influence of dopaminergic systems on cortical function extends beyond the known confines of the mesocortical dopaminergic system.
Animals↗
Metabolic mapping of functional activity in the hypothalamo-neurohypophysial system of the rat.
Physiological stimulation of the hypothalamo-neurohypophysial system by salt loading of rats resulted in a dramatically increased glucose utilization in the posterior pituitary but not in the paraventricular or supraoptic nuclei. The good correlation between glucose utilization and neural activity in the posterior pituitary (that is, nerve terminals) contrasted with the lack of correlation in the paraventricular and supraoptic nuclei (that is, the sites of the cell bodies of the same neurons). This difference in the metabolic response to functional activity between the two regions of these neurons can be explained by the differences in surface-to-volume ratios of these regions.
Animals↗
Cerebral glucose utilization: local changes during and after recovery from spreading cortical depression.
Cerebral glucose utilization is markedly increased in most areas of the cerebral cortex and reduced in many subcortical structures during spreading cortical depression. During recovery, cortical glucose utilization is still elevated, but the increased metabolic activity is distributed in columns running perpendicularly through the cortex.
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