Local Glucose Metabolism Research Articles

Effect of γ-Hydroxybutyrate on Local and Global Glucose Metabolism in the Anesthetized Cat Brain

This study addresses three topics in the chloralose-anesthetized cat: (a) distribution of local CMRglc: values ranging from 5 to 109 mumols/100 g/min were found in 37 brain structures and the mean CMRglc over all examined structures was 30.6 mumols/100 g/min; (b) effect of gamma-hydroxybutyrate (GHB, 250 mg/kg i.v.) on local CMRglc, which was significantly (p less than 0.05) depressed in 16 of 37 structures, most prominently in the auditory system, and the mean CMRglc over all structures after GHB was 20.4 mumols/100 g/min; and (c) global values of CMRglc, CMRO2, and CBF before and after GHB: in these experiments, a modified Kety-Schmidt technique was employed measuring saturation/desaturation of inhaled H2 and concentrations of glucose and oxygen in aortic and sagittal sinus blood. CBF and CMRO2 were not altered after GHB, whereas CMRglc was significantly decreased from 35.7 to 28.8 mumols/100 g/min. The values of CMRglc obtained with both techniques (autoradiography and the Kety-Schmidt technique) are concordant, especially when considering the different sampling areas of both methods. The main finding of the present study is a reduction in cerebral glucose consumption after GHB, irrespective of the technique of measurement. This reduction occurs at an unchanged CMRO2 and CBF.

Dopamine D 2 receptor agents, but not dopamine D 1, modify brain glucose metabolism

The effects of recently described selective dopamine D 1 and D 2 agonists and antagonists on brain glucose metabolism were studied using the 2-[ 14C]deoxyglucose autoradiographic technique. The administration of LY-141865 or YM-09151-2, which behave as a specific D 2 agonist and antagonist respectively, modified brain glucose metabolism in a manner similar to that previously described for more classical dopaminergic agents, such as apomorphine and haloperidol. In contrast, the administration of SKF 38393 or SCH 23390, a specific D 1 agonist and antagonist respectively, was not followed by significant modifications of brain glucose metabolism in any of the brain regions studied. These results indicate that D 2 but not D 1 dopamine receptors are involved in the regulation of local brain glucose metabolism.

Intercorrelations of glucose metabolic rates between brain regions: application to healthy males in a state of reduced sensory input.

We use a correlational analysis of regional metabolic rates to characterize relations among different brain regions. Starting with rates of local glucose metabolism (rCMRglc) obtained by positron emission tomography using [18F]fluorodeoxyglucose, we propose that the strength of the association is proportional to the magnitude of the correlation coefficient. Partial correlation coefficients, controlling for whole brain glucose metabolism, are used in the analysis. We also introduce a graphical technique to display simultaneously all the correlations, allowing us to examine patterns of relations among them. The method was applied to 40 very healthy males under conditions of reduced auditory and visual inputs (the "resting state"). Dividing the brain into 59 regions, and keeping only those partial correlation coefficients significant to p less than 0.01, we found the following: (a) All regions were significantly correlated with their contralateral homologues. For the most part, the largest partial correlation coefficients were between homologous brain regions. (b) Generally, the pattern of significant correlations between any two lobes in the left hemisphere did not differ statistically from the corresponding pattern in the right hemisphere. (c) Strong correlations were observed between primary somatosensory areas and premotor association areas. Correlations between these association areas and primary visual and auditory regions were not statistically significant. (d) Significant correlations between inferior occipital and temporal areas were found. Metabolic rates in the superior part of the occipital lobe were not correlated significantly with metabolic rates in regions of the temporal lobe, nor with metabolism in the parietal lobe. (e) As a whole, there were numerous correlations among frontal and parietal lobe regions, on the one hand, and among temporal and occipital lobe regions, on the other, but few statistically significant correlations between these two domains. We relate our results to various aspects of known brain anatomy, physiology, and cognitive functioning.

Methylphenidate decreases local glucose metabolism in the motor cortex

The local cerebral metabolism on glucose ( l-CMRg) was evaluated in animals given methylphenidate (15 mg/kg) in order to investigate possible mechanisms of action of the drug. Significant increases in l-CMRg ( p >0.05) were found in the globus pallidus, entopeduncular nucleus, substantia nigra, subthalamic nucleus, inferior olive, red nucleus, lateral cerebellar cortex, ventral lateral nucleus of the thalamus and the midbrain reticular formation. Significant decreases ( p >0.05) in l-CMRg were found in the motor cortex. These results suggest possible mechanisms for methylphenidate's action in attention deficit disorders.

Local cerebral glucose metabolism in newborn dogs: effects of hypoxia and halothane anesthesia.

Local cerebral glucose utilization (LCGU) was measured in 36 neuroanatomical structures of normal awake, halothane-anesthetized, and hypoxic newborn puppies by the autoradiographic 2-[14C]deoxyglucose method. In normal animals, LCGU was highest in the vestibular nucleus and in other gray matter nuclei of the brainstem and declined in a caudal-to-rostral progression through the neuraxis (i.e., LCGU of cerebellum greater than thalamus approximately equal to caudate-putamen greater than cerebral cortex). Lowest rates of glucose metabolism were detected in white matter structures. Halothane anesthesia (1.5% inspired) caused few changes in local glucose metabolism, the most notable being decreased LCGU among structures of the auditory system (cochlear nucleus, lateral lemniscus, inferior colliculus) and increased LCGU in the interpeduncular nucleus. Acute systemic hypoxia (arterial oxygen tension of approximately 12 mm Hg) produced markedly heterogeneous effects on local glucose metabolism: LCGU was increased in some gray matter structures, decreased in the thalamus, and substantially increased in the subcortical white matter and corpus callosum. In puppies whose brains were frozen in situ after 55 minutes of hypoxia, the concentration of lactate was increased ten- to elevenfold in cortical gray and subcortical white matter, but the concentrations of glucose, adenosine triphosphate, and phosphocreatine declined to a greater extent in the white matter. The results suggest that during hypoxia the high rate of glycolysis in white matter exceeded substrate supply so that glucose availability became the limiting factor for local energy production. Such a mechanism may contribute to the white matter injury that often develops following hypoxic-ischemic insults in the perinatal period.

New methods to determine the CNS effects of antigeriatric compounds: EEG topography and glucose use

AbstractBuchsbaum, M.S., J. Cappelletti, R. Coppola, F. Regal, A. C. King, and D. P. van Kammen: New methods to determine the CNS effects of antigeriatric compounds: EEG topography and glucose use. Drug Dev. Res. 2:489–496, 1982.It has previously been possible to measure regional glucose use in the cerebral cortex in animals only with autoradiographic techniques. With the advent of position emission tomography (PET) using (18F‐2DG) 18F‐2‐deoxyglucose, it is now possible to assess local glucose uptake in μmol/100 g tissue/min in normal volunteers or patients. The PET technique is complex and costly and cannot be repeated frequently because of the radiation dosage. However, local glucose use is closely tied to cerebral blood flow, and studies have related blood flow to EEG frequency measures. In this study, we have simultaneously investigated local glucose metabolism using 18F‐2DG with PET and EEG frequency with 16‐lead topographic mapping in six normal controls. Subjects sat in an acoustically treated darkened room with eyes closed for 10 min prior to, and 30 min following injection of 3–5 mCi 18F‐2DG. Following uptake, seven to eight horizontal scans parallel to the canthomeatal line were made. EEG recordings are made beginning 1 min after injection of the isotope and continuing for 30 min with 12 standard 10/20 system points on the left hemisphere and midline, and 4 additional points between existing posterior leads. Ten‐second EEG epochs are edited for artifacts and then analyzed by fast Fourier transform techniques. Using a cross‐sectional whole‐head atlas, a standardized, approximately equal‐area two‐dimensional representation of a lateral view of the brain was developed and 10/20 system scalp coordinates were projected onto it. EEG power estimates are interpolated for all points on this brain map. Using digital techniques, a 1‐cm‐thick cortical strip is peeled off each PET, slice and conformed to the lateral brain view, and values between strips are interpolated. The result is two simultaneously obtained electrophysiologic and metabolic lateral views of brain function displayed in gray‐scale values represented by dot density. In some subjects with eyes closed, alpha power is high in low glucose‐use regions, such as the occiput. Temporal regions appear low both in glucose use and in most power bands. Parallels between alpha distribution and glucose use are illustrated.

Regional protein synthesis in the rat brain during bicuculline-induced epileptic seizures.

The incorporation of L-[3,5-3H]tyrosine into cerebral proteins was investigated during the initial phase (30 min) of bicuculline-induced status epilepticus. Autoradiographs of different parts of the cerebral hemispheres, brain stem, and cerebellum were prepared. Marked local reduction of amino acid incorporation was evident in bilaterally symmetrical areas of the cerebral cortex, hippocampus, thalamic nuclei, and the region of the medial geniculate body. No apparent difference of local [3H]tyrosine incorporation was observed in the lower brain stem nuclei and in the cerebellum of control and convulsed animals. The territories showing a decrease of protein synthesis during epileptic seizures coincide largely with the regions of maximal local glucose metabolism and cerebral blood flow. The present investigation demonstrates that autoradiography of regional protein biosynthesis is a suitable method for the visualization of neuronal populations at risk in the very early stages of seizure activity.

The effect of scopolamine on local glucose metabolism in rat brain

The effects of the muscarinic acetylcholine inhibitor scopolamine on local cerebral glucose metabolism (LCMRG) was examined. Scopolamine, 0.4 mg/kg, was injected intravenously into male Wistar rats 25 min prior to metabolic studies. The autoradiographic [ 14C]2-deoxyglucose technique was used to measure LCMRG in 5 experimental and 5 control animals. An analysis of variance was performed to test for significant regional differences. The following decreases in LCMRG expressed as a percentage change from control values were observed. The greatest decrease occurred in the globus pallidus (57.5%, P < 0.005) while the caudate nucleus only decreased to 82.6% ( P < 0.05). This may correlate with proposed cholinergic extrapyramidal pathways. Ammons Horn of hippocampus decreased to 61.1% ( P < 0.005) and the dentate gyrus to 71.8% ( P < 0.005). These are proposed cholinergic limbic pathways from the septal nuclei. The marked effect on Ammons Horn may also relate to the specific impairment of recent memory induced by scopolamine. The auditory (67.3%), frontal (70.7%) and parietal cortex (70.1%) and the lateral thalamus (73.1%) were all significantly depressed ( P < 0.005), which may be related to the proposed role of cholinergic pathways in the reticular activating system. Changes in the limbic structures including the hypothalamus (75.0%, P < 0.01), mamillary body (75.1%, P < 0.01), septal nuclei (80.5%, P < 0.05) and nucleus accumbens (89.0%, P > 0.05) were not as marked. Brain stem and cerebellar structures were not significantly affected.