Rates Of Cerebral Glucose Utilization Research Articles

Effects of stimulation of the striatum and globus pallidus on local cerebral glucose utilization in rats

Divergent ethanol-drinking behavior in rats selectively bred for high- or low-ethanol-drinking behavior could be related to differences in the sensitivity of the CNS to ethanol. In the current study, we examined the effects of acute (i.e., single injection) ethanol administration on local cerebral glucose utilization (LCGU) within selected brain regions of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats. Adult, male, HAD and LAD rats from replicate line 2 were injected intraperitoneally with saline, or ethanol, at doses of 0.25 g/kg or 1.0 g/kg, during their dark cycle; 10 min later, [14C]-2-deoxyglucose ([14C]-2-DG; 125 μCi/kg) was injected into the femoral vein. Timed arterial blood samples were collected over 45 min and assayed for plasma glucose, ethanol, and [14C]-2-DG levels. Rats were then decapitated, and their brains were quickly extracted and frozen in isopentane at –50°C. Coronal brain sections were prepared and apposed to x-ray film for 2 days, and image densities were determined by using quantitative autoradiography. Data were collected from several key limbic (nucleus accumbens, ventral tegmental area, olfactory tubercle, amygdala, hippocampus, ventral pallidum, and septum), basal ganglia, cortical (medial prefrontal, frontal, parietal, temporal, occipital, entorhinal, piriform, and cingulate), and subcortical (thalamus, habenula, and superior colliculus) structures. After administration of both low (0.25 g/kg) and moderate (1.0 g/kg) doses of ethanol, LCGU values were lower, relative to those for saline controls, in several CNS regions (lateral septum; posterior cingulate, frontal, parietal, and temporal cortices; dorsomedial striatum; and dorsomedial thalamus) of LAD but not HAD rats. These findings may indicate that certain CNS regions of LAD-2 rats are more sensitive than regions of HAD-2 rats to the effects of low-to-intermediate doses of ethanol.

Effects of stimulation of the striatum and globus pallidus on local cerebral glucose utilization in rats

Effects of stimulation of the striatum and globus pallidus on local cerebral glucose utilization in rats

Correlation between brain surface potassium and glucose utilization after bilateral cerebral ischemia in the gerbil.

The correlation between cerebral glucose utilization and brain surface potassium concentration (BS-K+) was studied during reperfusion following bilateral cerebral ischemia in the gerbil. Cerebral glucose utilization rate was measured by the 14C-2-deoxyglucose method and BS-K+ was continuously monitored by a potassium sensitive membrane electrode. BS-K+ increased from 3.0 +/- 0.6 mM (mean +/- S.D.) before ischemia to 58.7 +/- 17.3 mM 30 minutes after the occlusion of both common carotid arteries. The rate of decline of BS-K+ after release of occlusion differed between animals. Glucose utilization rate in the cerebral cortex immediately under the potassium electrode was low but homogeneous in 7 animals while in 5 animals the metabolic pattern was heterogeneous with areas of both low and high glucose metabolism. The former animals exhibited a fast recovery of potassium flux while the latter animals showed a slow recovery. Glucose utilization rate and potassium half recovery time were linearly correlated. These studies suggest that the reason that potassium flux may not recover rapidly in postischemic brain tissue is due to the lack of sufficient energy for a rapid re-establishment of the ion gradient across the cell due to the inefficient energy production of anaerobic glycolysis.

Local cerebral glucose utilization rate following intermittent exposures to 2 atmosphere absolute oxygen

Previous studies have shown significant increases in regional cerebral metabolic rate for glucose (rCMRgl) in 14 of 28 investigated brain structures in rats exposed to 1-h oxygen at 2 atmosphere absolute (ATA O 2). Continuous 4-h exposure to 2 ATA O 2 resulted in significant increases only in superior olivary nucleus and inferior colliculus. In the present study, the rCMRgl was autoradiographically measured by the [ 14C]2-deoxyglucose technique during the last 30 min of 4 intermittent 1-h exposures to either 2 ATA O 2 or air at atmospheric pressure, with 3 h of breathing air outside the pressure chamber between each oxygen or air exposure. Statistically significant reductions in rCMRgl of the oxygen-exposed rats were observed in superior olivary nucleus and inferior colliculus, while no changes were observed in 26 other investigated structures. The previously observed increases in rCMRgl in a single 1- or 4-h exposure at 2 ATA O 2 were reduced or reversed during the intermittent hyperbaric oxygen exposure. The relation of the observed changes in rCMRgl during single and intermittent hyperbaric oxygen exposures to the extension of tolerance to hyperbaric oxygenation is discussed.

Effects of systemically administered cholecystokinin-octapeptide on local cerebral metabolism

The effects of systemically administered cholecystokinin-octapeptide on local cerebral glucose utilization in rats were studied by means of the 2−[ 14 C]deoxyglucose method. Decreases in cerebral glucose utilization were observed in discrete regions of the cerebral cortex, mesencephalon, and brainstem, including the lateral habenula, ventral tegmental area, substantia nigra pars compacta, and the nucleus of the solitary tract. These data demonstrate changes in metabolic activity in specific cerebral regions following systemic cholecystokinin administration.

Metabolic Mapping of the Brain During Rewarding Self-Stimulation

Local rates of cerebral glucose utilization were measured in rats by the quantitative 2-deoxy-D-[14C]glucose autoradiographic method during electrical stimulation of the ventral tegmental area. Rats trained in intracranial self-stimulation showed a pattern of changes in forebrain metabolic activity distinctly different from the pattern seen in rats stimulated by the experimenter. These findings provide information about the distribution of local cerebral activity specific to reinforced instrumental behavior.

Regional cerebral glucose utilization rates in rats during asymptomatic period of exposure to 1, 2 and 3 atmospheres absolute of oxygen

A previous study has shown an increase in regional cerebral metabolic rate for glucose prior to the onset of central nervous system oxygen toxicity in rats exposed to 5 atmospheres absolute of oxygen. The present study was designed to measure regional cerebral glucose utilization rates at pressures used for oxygen therapy and prolonged exposures during which rats are known to be asymptomatic. The regional metabolic rate for glucose in 26 brain structures and in gray and white matter of the thoracic and lumbar spinal cord was autoradiographically measured in awake unrestrained rats using the autoradiographic [ 14C]2-deoxyglucose technique. Femoral artery and vein cannulae were inserted 3 days before the experiment. Rats were divided into.four groups of 15: (a) air control; (b) 6 h at 1 atmosphere absolute oxygen; (c) 4 h at 2 atmospheres oxygen; and (d) 2 h at 3 atmospheres oxygen. Statistically significant increases in glucose utilization ( p < 0.05) are seen only in lateral thalamus at 3 atmospheres oxygen, in superior olivary nucleus and inferior colliculus at 2 atmospheres oxygen and in superior olivary nucleus at 1 atmosphere oxygen. The combination of our previous data at 5 atmospheres oxygen and the present results at prolonged and safe exposures to lower pressures indicated that increased glucose utilization in some neuronal structures precedes the onset of the central nervous system manifestations of oxygen toxicity

Down's syndrome in adults: brain metabolism.

The cerebral metabolic rate for glucose, as measured with positron emission tomography and fluorine-18-labeled 2-deoxy-D-glucose, was significantly higher in four healthy young subjects with trisomy 21 syndrome (Down's syndrome) than the mean rate in healthy young controls. The rate of cerebral glucose utilization in the frontal lobe of a 51-year-old subject with Down's syndrome was significantly lower than the rate in the young subjects with this syndrome, but approximated the rate in middle-aged controls. Thus glucose utilization by the brain appears to be excessive in young adults with Down's syndrome but may decline with age in some brain regions.

Local cerebral glucose consumption in the rat. I. Effects of halothane anesthesia.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-(1-14C)glucose technique in normal rats under light halothane-anesthesia. Three types of region-specific metabolic alterations were elicited by inhalation of 0.5% halothane. The most striking effect observed was a significant increase of glucose consumption within the locus coeruleus, substantia nigra compacta and reticulata, interpeduncular nucleus, hippocampus, and fornix of the anesthetized animals in comparison to the corresponding brain areas of the conscious control rats. Halothane-anesthesia was also associated with significant metabolic depression in 21 (out of the 74 examined) discrete regions of the rat brain, distributed within the pons, cerebellum, diencephalon, and cortex, and was more prevalent in thalamus and neocortex. However, halothane failed to alter consistently the rates of glucose utilization in the rest of the rat brain areas investigated. The present findings suggest that halothane specifically alters the regional cerebral glucose utilization, with some limbic system components and the basal ganglia displaying increased metabolism, in contrast to the sensorimotor system which demonstrates significantly decreased metabolic activity.

Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years.

Positron emission tomography (PET) scanning with 18F-2-deoxy-D-glucose was employed to examine hemispheric and regional rates of cerebral glucose utilization in 21 resting healthy men between the ages of 21 and 83 years. The eyes of the subjects were covered and the external auditory canals were plugged with cotton in the 45 minutes following injection of tracer. Mean hemispheric cerebral metabolic rates for glucose (CMRglc) averaged 4.3 to 4.4 mg x 100 g-1 X min-1, and mean hemispheric grey matter glucose utilization, (CMRglc)grey, averaged 5.2 to 5.3 mg x 100 g-1 X min-1. Neither parameter was correlated significantly with age, nor were their right/left ratios correlated with age (P greater than 0.05). The mean ratios, furthermore, did not differ significantly from 1. Regional cerebral metabolic rates for glucose, rCMRglc, at each of 31 identified midline and bilateral structures also were not correlated significantly with age. Mean rCMRglc ranged from 2.6 mg X 100 g-1 X min-1 at the centrum semiovale to 6.2 mg . 100 g-1 X min-1 at the precentral gyrus of the frontal lobe and precuneus of the parietal lobe. The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.

A potential error in modifications of the [ 14C]2-deoxyglucose technique

Although the technique developed by Sokoloff et al. 21 employing [ 14C]2-deoxyglucose as tracer, provides measurements of local cerebral glucose utilization, various modifications of the original technique are presently in widespread use. We have examined the validity of a crucial simplifying assumption which is an integral feature of many of these modifications; namely, that all the radioisotope in the CNS at the moment of sacrifice is present as 2-deoxyglucose-6-phosphate. By employing the kinetic model developed by Sokoloff et al. 21 and arterial plasma [ 14C]2-deoxyglucose and glucose histories, the proportion of total radioactivity present in the CNS as unphosphorylated 2-deoxyglucose was calculated and found to vary from 5 to 50% of the total amount of isotope present in the CNS under different experimental conditions. It can be shown to be dependent upon (a) the rate of cerebral glucose utilization, (b) the time which elapses from administration of the radioisotope until the sacrifice, (c) the route by which the isotope is administered, and (d) arterial plasma glucose levels. Thus, modifications of the original 2-deoxyglucose technique have introduced a potential source of error which is not a feature of the approach of Sokoloff and his associates.

Effect of nitrous oxide on local cerebral glucose utilization in rats.

The influence of 70-80% N2O on local local cerebral glucose utilization (CMRg1) in the rat brain was studied with the [14C]deoxyglucose method in minimally restrained, spontaneously breathing animals 75 min following discontinuation of halothane anaesthesia. Nitrous oxide was found to have only small effects on local CMRg1 in the majority of the 25 structures analyzed. When corrections were made for a small difference in body temperature between nitrous oxide--breathing animals and those breathing air nitrous oxide was found to significantly increase local CMRg1 in some subcortical structures by 15-25% (red nucleus, thalamus, geniculate bodies, and superior colliculus), and to decrease local CMRg1 in nucleus accumbens and sensorimotor cortex by comparable amounts. Thus, although nitrous oxide does not alter overall glucose utilization in the brain, it differentially affects CMRg1 in some brain structures.

Measurement of cerebral glucose utilization using washout after carotid injection in the rat.

The carotid injection technique, used previously to quantitate the kinetics of blood-brain barrier transport of metabolic substrates, may be modified to analyze the rate of cerebral glucose utilization. A 0.2-ml solution of [14C]glucose (GF) and [3H]methylglucose (M), an internal reference, is rapidly injected into the carotid artery, followed by microwave fixation of brain at various times up to 4 min after injection. The brain radioactivity is separated into a fraction containing neutral hexoses (GF and M) and a fraction containing metabolites of glucose. The GF/M ratio is related to the rate constant (k3) of brain glucose utilization by the simple, linear equation: 1n(GF/M) = ln(GF0/0)--k3t, where GF0/M0 = the brain uptake index of glucose, relative to methylglucose, at 5--15 s after injection, and t = the time after carotid injection, e.g., 1--4 min. It is assumed that (a) the rate of influx due to recirculation of label is minimal during the 4-min circulation period; and (b) the rate constants of glucose efflux (k2) and methylglucose efflux (k2*) are identical. Independent estimates of k2 and k2* showed these parameters to be identical: k2 = 0.14 +/- 0.08 min-1; k2* = 0.14 +/- 0.02 min-1. A logarithmic plot of GF/M ratios versus time was linear (r = 0.99), and was described by the slope k3 = 0.21 +/- 0.02 min-1. Assuming glucose is uniformly distributed in brain, then the glycolytic rate = k3 x brain glucose = (0.21 min-1) (2.6 mumol g-1) = 0.55 mumol min-1 g-1 for the cortex of the barbiturate-anesthetized rat. These studies provide the basis for a simple method of measurement of regional brain glycolysis that does not require either the use of correction factors, e.g., the lumped constant, or the use of differentially labeled glucose.

The central noradrenergic system in the rat: Metabolic mapping with α-adrenergic blocking agents

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose technique in 73 normal, awake rats treated with different doses of the alpha-adrenergic blockers, phenoxybenzamine, phentolamine and yohimbine. Three types of responses were elicited by the administration of these drugs. The predominant effect observed after administration of all alpha-blockers was a widespread depression of glucose utilization, particularly within the neocortex. The effect was most pronounced with phenoxybenzamine. In a few structures (locus coeruleus, interstitial nucleus of the stria terminalis, medial forebrain bundle, periventricular nucleus and some medullary and hypothalamic nuclei associated with the regulation of blood pressure) marked increases in glucose utilization were observed. Administration of phentolamine resulted in increased glucose utilization in all the central components of the auditory system (cochlear n., superior olivary n., n. lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). Phenoxybenzamine and yohimbine tended to decrease glucose utilization in the auditory system. Alternating columns with higher and lower rates of local glucose consumption were observed in most of the neocortical areas and in the cerebellar vermis. The significance of these columns is not clear.

Effects of ethanol and temperature on glucose utilization in the in vivo and isolated perfused mouse brain.

A [14C]2‐deoxy‐d‐glucose technique was used to investigate the effects of ethanol and temperature variation on the rate of glucose utilization in the isolated perfused mouse brain. Glucose utilization rates in six regions of the isolated perfused mouse brain at 37°C were similar to the rates in comparable regions of the in vivo mouse brain. The temperature dependence of the glucose utilization rate in the perfused mouse brain suggests that a change in the rate‐limiting step of cerebral glucose metabolism occurred between 28°C and 32°C. To investigate the possible involvement of temperature‐dependent membrane phase transitions, brain perfusions were performed with a medium containing ethanol which is known to increase membrane fluidity. Perfusion of the mouse brain with a fluid containing 87 mm ethanol (400 mg/dl) resulted in decreases in the glucose utilization rates at 37°C but not at 28°C. At 28°C, ethanol produced an increase in glucose utilization in the medulla‐pons and in the cerebellum of perfused brains. In vivo rates of cerebral glucose utilization in two lines of mice selectively bred for differences in ethanol‐induced sleep time indicated that no differences in basal metabolism or following a 4‐g/kg dose of ethanol existed between the two lines. Interpretations of ethanol's differential effects on cerebral glucose utilization rates in the isolated perfused mouse brain at 28°C and 37°C are presented along with a discussion of the apparent discrepancies observed when in vivo and perfused brains are treated with equivalent concentrations of ethanol.

Accurate measurement of cerebral metabolism in the conscious, unrestrained neonatal piglet. II. Glucose and oxygen utilization.

Cerebral utilization rates of glucose and oxygen were measured in 18 conscious, unrestrained neonatal piglets. Cerebral glucose utilization rate was 26.9 ± 2.8 μmol/min/100g (mean ± SEM), cerebral oxygen utilization rate was 160 ± 10 μmol/min/ 100 g and the glucose to oxygen ratio was 1.03 ± 0.11, implying that glucose is the primary substrate for cerebral metabolism in the normal neonatal piglet at rest. These results are similar to the data obtained in the few studies of cerebral metabolism in the human infant and encourage the continued use of the piglet as a suitable animal model.

Functional Plasticity in the Immature Striate Cortex of the Monkey Shown by the [ 14 C]Deoxyglucose Method

Autoradiographic representation of the local rates of cerebral glucose utilization and local cerebral functional activity by means of the [14C]deoxyglucose technique reveals the existence of the ocular dominance columns in the striate cortex of the monkey in the first day of life. In contrast to the stability of these columns in more mature brain, monocular deprivation for 3 months from the first day of life results in their complete disappearance and a reversion of the autoradiographic pattern to that seen in animals with normal binocular vision. These results are consistent with a reorganization of the representation of the visual fields of the two eyes in the striate cortex and provide additional evidence of the plasticity of the striate cortex of the monkey in early life.

Effects of gamma-butyrolactone on local cerebral glucose utilization in the rat.

Abstract— The effects of graded doses of γ‐butyrolactone on the rates of glucose utilization in 29 structural components of the albino rat brain were studied by means of the [14C]deoxyglucose technique. The γ‐butyrolactone in doses of 75, 150, 300, and 600 mg/kg of body weight was administered intravenously in divided doses, two‐thirds 45min and one‐third 15min before the administration of the pulse of [14C]deoxyglucose. Electroencephalographic recordings were carried out in some of the rats administered each of the above doses. The results demonstrate dose‐dependent changes in the level of consciousness, electroencephalographic activity, and the rates of local cerebral glucose utilization. At the two lower doses there were no notable effects on behavior, but there was significant slowing of the electroencephalogram. The higher doses caused a trance‐like state associated with long periods of electroencephalographic silence punctuated by bursts of polyspike and wave activity. At all doses there was significant depression of the rates of cerebral glucose utilization throughout the brain, the greater the dose the greater the magnitude of the depression. The effects were greater in gray structures than in white matter. At the maximum doses local cerebral glucose utilization was profoundly depressed to mean values of 32% and 58% of control values in gray and white matter, respectively. There was no apparent selectivity or specificity in the effects of γ‐butyrolactone on glucose utilization in the various gray structures of the brain; all 26 gray structures studied exhibited similar dose‐response relationships. Animals similarly treated with γ‐butyrolactone and left undisturbed regained completely normal behavior and electroencephalographic activity in several hours. These results suggest that γ‐butyrolactone profoundly depresses cerebral energy metabolism throughout the brain and that it might prove useful in clinical conditions in which a temporary reversible reduction in cerebral energy demand is desired.

Cerebral O 2 , CO 2 , regional cerebral vascular control, and hyperbaric oxygenation.

ArticleCerebral O 2 , CO 2 , regional cerebral vascular control, and hyperbaric oxygenation.J W Bean, J Lignell, and D W BurgessJ W Bean, J Lignell, and D W BurgessPublished Online:01 May 1972https://doi.org/10.1152/jappl.1972.32.5.650MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySpontaneous Development of CSD Related to Brain Pathophysiological Conditions20 October 2022Oxygen-induced mitochondrial biogenesis in the rat hippocampusNeuroscience, Vol. 137, No. 2Effects of 7-nitroindazole and N-nitro-l-arginine methyl ester on changes in cerebral blood flow and nitric oxide production preceding development of hyperbaric oxygen-induced seizures in ratsNeuroscience Letters, Vol. 382, No. 3Oxygen tension under hyperbaric conditions in healthy pig brain6 May 2003 | Clinical Physiology and Functional Imaging, Vol. 23, No. 3Behavioral effects of 7-nitroindazole on hyperbaric oxygen toxicityPhysiology & Behavior, Vol. 76, No. 4-5Changes in nitric oxide production and cerebral blood flow before development of hyperbaric oxygen-induced seizures in ratsBrain Research, Vol. 918, No. 1-2Effect of MK-801 on Seizures Induced by Exposure to Hyperbaric Oxygen: Comparison with AP-7Toxicology and Applied Pharmacology, Vol. 151, No. 2Toxic Effects of OxygenHyperbaric oxygne tolerance in newborn mammals-hypothesis on mechanisms and outcomeFree Radical Biology and Medicine, Vol. 14, No. 6Oxygen toxicity and reactive oxygen metabolites in mammalsFree Radical Biology and Medicine, Vol. 7, No. 1A mathematical simulation of oxygen delivery in rat peripheral nerveMicrovascular Research, Vol. 34, No. 2Central nervous system glucose utilization rate during oxygen-induced respiratory changes at 2 atmospheres oxygen in the ratJournal of the Neurological Sciences, Vol. 76, No. 2-3Regional cerebral glucose utilization rates in rats during asymptomatic period of exposure to 1, 2 and 3 atmospheres absolute of oxygenNeuroscience, Vol. 11, No. 4Oxygen Pressure and Ictal Activity in the Cerebral Cortex of Artificially Ventilated Rats during Exposure to Oxygen High Pressure16 April 2012Responses of human limbic neurons to induced changes in blood gasesBrain Research, Vol. 132, No. 1Changes in the electrical activity and Po2 of the rat's brain under high oxygen pressureExperimental Neurology, Vol. 50, No. 2Variability of partial pressures of CO2 and O2 in resting skeletal muscleMicrovascular Research, Vol. 10, No. 2Auditory and visual evoked potentials during hyperoxiaElectroencephalography and Clinical Neurophysiology, Vol. 37, No. 4Oxygen poisoning in the unanesthetized brain: Correlation of the oxidation-reduction state of pyridine nucleotide with electrical activityBrain Research, Vol. 76, No. 3Dynamics and Control Mechanisms in Maintenance of Regional Cerebral Blood FlowStroke, Vol. 5, No. 4A Contribution to the Physiology of the Perilymph Part II: Cochlear and Cerebral Blood Flow28 June 2016 | Annals of Otology, Rhinology & Laryngology, Vol. 83, No. 2 More from this issue > Volume 32Issue 5May 1972Pages 650-7 https://doi.org/10.1152/jappl.1972.32.5.650PubMed4556851History Published online 1 May 1972 Published in print 1 May 1972 Metrics