2DG Uptake Research Articles

Transport of 1,5-anhydro-D-glucitol across plasma membranes in rat hepatoma cells.

The transport of 1,5-anhydro-D-glucitol (AG) across plasma membranes was investigated in rat hepatoma cells, Reuber H-35. The AG uptake by the cells showed a concentration gradient dependency: the uptake was saturated within 40 s, which was less than one-third of the saturation time for 2-deoxy-D-glucose (DG) uptake. Furthermore, the Km value of the transport system for AG was higher than 100 mM. Though AG has a pyranoid structure resembling that of glucose, AG did not compete for cellular uptake with DG, D-glucose or 3-O-methyl-D-glucose, which are taken into cells through the glucose transporters. Conversely, the DG transport was not inhibited by AG at concentrations up to 50 mM. AG transport was hardly inhibited by 10 microM cytochalasin B, which strongly inhibits glucose transporters. In contrast, the AG transport was inhibited by 100 microM phloretin much more strongly than the DG transport when cells were preincubated with the inhibitor; the inhibition constant was 28.0 microM. The AG transport was not inhibited by 100 microM phloridzin, while the DG uptake was slightly inhibited by phloridzin. On the basis of these observations we propose that the AG uptake into rat hepatoma cells is mediated by a carrier distinct from glucose transporters.

Effect of insulin on [3H]deoxy-D-glucose pharmacokinetics in the rat.

Despite its increasing use in physiological animal investigations, there has been no systematic study of the whole body kinetics of 2-deoxy-D-glucose (2DG) or its modification by insulin. A previously proposed model that included processes representing transport across cell walls and intracellular phosphorylation of 2DG was investigated. The model predictions were compared with the plasma disappearance of 2DG observed in the rat following intravenous bolus injection. Experiments were performed during euglycemia at varying levels of hyperinsulinemia. The model was adequate to describe empirically the experimental data after a correction was made for urine loss. However, the variation in model parameters with plasma insulin concentration was not consistent with the expected action of insulin on cellular efflux. A possible explanation could be a shift in the rate-limiting step from glucose transport to another prephosphorylation process under conditions of high tissue uptake. This suggests that either intracellular or extracellular diffusion may constitute a significant barrier to 2DG (and glucose) uptake under some conditions.

Progressive activation of paratrigeminal nucleus during entrance to hibernation.

The paratrigeminal nucleus (Pa5) undergoes a progressive increase in its uptake of 2-[14C]deoxyglucose (2DG) relative to other brain structures during entrance to hibernation in the ground squirrel. This highly significant increase results in the Pa5 becoming the most highly labeled brain region during hibernation, even though it exhibits one of the lowest levels of 2DG uptake in the brain during the nonhibernating state. The progressive activation of the Pa5 observed during entrance is reversed during arousal from hibernation. These observations and the neuroanatomical projections of the Pa5 implicate this nucleus as playing a role in the entrance and maintenance of the hibernating state.

Functional anatomy of macaque striate cortex. III. Color

Using spatially diffuse stimuli (or sinusoidal gratings of very low spatial frequency), levels of 14C-2-deoxy-d-glucose (DG) uptake produced by color-varying stimuli are much greater than those produced by luminance-varying stimuli in macaque striate cortex. Such a difference in DG results is consistent with previous psychophysical and electrophysiological results from man and monkey. In DG experiments with color-varying gratings of low and middle spatial frequencies, or with spatially diffuse color variations, DG uptake was highest in the cytochrome oxidase blobs, as was also seen with low-spatial-frequency luminance gratings. High-spatial-frequency, color-varying uptake patterns were shifted to cover both blob and interblob regions in a manner similar to that of the patterns obtained with middle-spatial-frequency luminance stimuli. However, in no instance did chromatic gratings produce uptake restricted to the interblob regions, as with the pattern seen with the highest-spatial-frequency luminance gratings. Thus, DG uptake is relatively higher in the interblob regions when comparing luminance with color-varying gratings that are otherwise similar. It was also possible to show DG evidence for receptive-field double-opponency in the upper-layer blobs, but color sensitivity in layer 4Cb appears single-opponent. The DG results suggest that color sensitivity is also high in the lower-layer (layers 5 + 6) blobs, and that many layer 5 receptive fields are double-opponent. Striate layers 4Ca and 4B-appeared color-insensitive in a wide variety of DG tests; this supports the idea of a color-insensitive stream running from the magnocellular LGN layers through striate layers 4Ca and 4B to extrastriate areas MT and V3. There was also a major effect due to wavelength: long and short wavelengths produced much more uptake than did middle wavelengths, even when all colors were equated for luminance and saturation. No variation with eccentricity was seen in cortical color sensitivity, at least between 0 degrees and 10 degrees.

Functional anatomy of macaque striate cortex. V. Spatial frequency

When macaque monkeys view achromatic, sinusoidal gratings of a single spatial frequency, the pattern of 14C-2-deoxy-d-glucose (DG) uptake produced by the gratings is shown to depend on the spatial frequency chosen. When a relatively high (5-7 cycles/deg) spatial frequency is shown binocularly at systematically varied orientations, uptake in parafoveal striate cortex is highest between the cytochrome oxidase blobs (that is, in the interblobs) in layers 1, 2, and 3. In layers 4B, 5, and 6, where the cytochrome oxidase blobs are faint or absent, DG uptake is highest in a periodic pattern that lies in register with the interblobs of layers 2 + 3. When the grating is, instead, of relatively low (1-1.5 cycles/deg) spatial frequency, DG uptake is highest in the blobs, in the blob-aligned portions of layers 1-4B, and in the lower-layer blobs as well. These variations in DG topography are confirmed in stimulus comparisons within a single hemisphere. Presumably, this shift in functional topography within the extra-granular layer is the primate homolog of "spatial frequency columns" shown earlier in the cat (Tootell et al., 1981; Silverman, 1984). In the well-differentiated architecture of primate striate cortex, laminar differences produced by high- versus low-spatial-frequency gratings are visible as well. Gratings of very high spatial frequency produce much higher uptake in 4Cb (which receives input from the parvocellular LGN layers) than in 4Ca (which gets its input from the magnocellular LGN layers). Gratings of low spatial frequency produce the converse result. Presumably, cells in the magnocellular LGN layers and/or in the magnocellular-dominated layer 4Ca have lower average spatial frequency tuning (larger receptive fields) than their counterparts in the parvocellular LGN and/or in striate layer 4Cb. The DG patterns produced by various spatial frequencies also vary with eccentricity, in a manner consistent with known, eccentricity-dependent variations of receptive-field size and spatial frequency tuning. Thus, gratings of a "middle"-spatial-frequency range (4-5 cycles/deg) produce high uptake in the blobs near the foveal representation and high uptake in the interblobs at more peripheral eccentricities, including 5 degrees. This shift in DG topography also includes the transition zone near 3 degrees, where the level of stimulus-driven uptake is as high in the blob regions as it is in interblob regions. Variations in uptake between layers 4Ca and 4Cb, as a function of eccentricity, shift in parallel with the changes in the upper-layer topography.

Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions

A series of experiments was carried out using 14C-2-deoxy-d-glucose (DG) in order to examine the functional architecture of macaque striate (primary visual) cortex. This paper describes the results of experiments on uptake during various baseline (or reference) conditions of visual stimulation (described below), and on differences in the functional architecture following monocular versus binocular viewing conditions. In binocular "baseline" experiments, monkeys were stimulated either (1) in the dark, (2) with a diffuse gray screen, or (3) with a very general visual stimulus composed of gratings of varied orientation and spatial frequency. In all of these conditions, DG uptake was found to be topographically uniform within all layers of parafoveal striate cortex. In monocular experiments that were otherwise similar, uptake was topographically uniform within the full extent of the eye dominance strip, in all layers. Certain other visual stimuli produce high uptake in the blobs, and still another set of visual stimuli (including high-spatial-frequency gratings) produce highest uptake between the blobs at parafoveal eccentricities, even in an unanesthetized, unparalyzed monkey. Eye movements per se had no obvious effect on striate DG uptake. Endogenous uptake in the blobs (relative to that in the interblobs) appears higher in the squirrel monkey than in the macaque. The pattern of DG uptake produced by binocular viewing was found to deviate in a number of ways from that expected by linearly summing the component monocular DG patterns. One of the most interesting deviations was an enhancement of the representation of visual field borders between stimuli differing from each other in texture, orientation, direction, etc. This "border enhancement" was confined to striate layers 1-3 (not appearing in any of the striate input layers), and it only appeared following binocular, but not monocular, viewing conditions. The border enhancement may be related to a suppression of DG uptake that occurs during binocular viewing conditions in layers 2 + 3 (and perhaps layers 1 and 4B), but not in layers 4Ca, 4Cb, 5 or 6. Another major class of binocular interaction was a spread of neural activity into the "unstimulated" ocular dominance strips following monocular stimulation. Such an effect was prominent in striate layer 4Ca, but it did not occur in layer 4Cb. This "binocular" spread of DG uptake into the inappropriate eye dominance strip in 4Ca may be related to the appearance of orientation tuning and orientation columns in that layer. No DG effects were seen that depended on the absolute disparity of visual stimuli in macaque striate cortex.

Common fur and mystacial vibrissae parallel sensory pathways: 14 C 2-deoxyglucose and WGA-HRP studies in the rat.

Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex. Common fur stimulation above the whiskers activated a cortical region between the SI and SII whisker activated regions of cortex. It is proposed that this region represented the combined SI and SII common fur regions of somatosensory neocortex. Both whisker and common fur stimulation activated all layers of cortex, with layer IV being most activated followed by II-III, V, and VI. These data indicate that sensory input from the mystacial vibrissae in the adult rat is processed in brainstem, thalamic, and cortical pathways which are predominantly parallel to those which process information from the neighboring common fur sensory receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential glucose utilization in the parafascicular region during slow-wave sleep, the still-alert state and locomotion

Regional cerebra3 glucose utilization (CGU), detectable by the uptake of 2-deoxy-[ 14C]glucose ([ 14C]2DG), was examined during 3 behavioral states—slow-wave sleep (SWS), the still-alert state (SAL) and locomotion (LOC). Examination of the autoradiograms, generated by exposing the [ 14C]2DG incorporated brain sections to Kodak Royal X Pan film revealed a high level of uptake bilaterally and discretely in the parafascicular (PF) region during these behaviors. This pattern of [ 14C]2DG uptake does not correspond to any of the anatomical structures previously identified by histo- and cytochemical methods, including the [ 14C]2DG method. Further, optical density measurements of this region indicated that the [ 14C]2DG uptake was significantly lower during SWS than during SAL or LOC. The present finding is compatible with the interpretations of previous physiological and behavioral studies that there is an inhibition by cells at the PF relay to the dentate gyrus that is lowered during the SWS compared to the SAL state, thus allowing preferential brain-stem activation of the dentate gyrus.

Localized changes in olfactory bulb morphology associated with early olfactory learning.

Young rats exposed to an odor while receiving reinforcing stimulation come to approach that odor upon subsequent presentation. In addition, such pups have increased 14C-2-deoxyglucose (2DG) uptake within focal areas of the glomerular layer in response to that odor, compared to control animals experiencing the odor for the first time. In this study, the morphology of the glomerular areas underlying these 2DG foci was examined to determine whether early olfactory learning imposed local structural changes that could produce the enhanced 2DG uptake. Alternate sections either were processed with a silver and a Nissl stain to label both cell bodies and their processes or were histochemically treated for the mitochondrial enzymes cytochrome oxidase (CO) or succinic dehydrogenase (SDH) to define the glomerular core of the bulb; 2DG autoradiographs were aligned with adjacent stained sections, and regions underlying the high 2DG uptake foci were examined. In odor-familiar animals, large glomerular clusters that protruded into the external plexiform layer or the olfactory nerve layer were associated with the focal areas of increased 2DG uptake. Morphometric analysis of these regions revealed that the glomerular layer underlying the foci of high 2DG uptake was 30% wider in odor-familiar animals than comparable areas in odor-unfamiliar animals; the cross-sectional areas of individual glomeruli were 21% larger in odor-familiar animals. The foci of enhanced 2DG uptake therefore appear to be associated with groups of enlarged glomeruli. These data demonstrate that early olfactory learning influences the morphology of the olfactory bulb.

Glucose and amino acid uptake by exercising muscles in vivo: effect of insulin, fiber population, and denervation.

The first series of experiments was performed on control rats. The animals were injected iv with trace amounts of 2-deoxy-D-[1-14C]glucose [( 14C]DG) or alpha-[1-14C] aminoisobutyric acid with or without 0.1 U insulin/rat, and calf muscles of the right hindlimb were electrically stimulated to induce 1 contraction/sec. The exercise was discontinued 25 min after the injection, and cellular uptakes of DG or aminoisobutyric acid by soleus, plantaris, and gastrocnemius muscles in disintegrations per min/mg dry tissue weight were determined. The results of these experiments demonstrated that basal, insulin-induced, and exercise-induced uptakes of glucose and amino acids by muscles are dependent on muscle fiber population, and the stimulatory effects of exercise and insulin on soleus and plantaris muscles, but not gastrocnemius muscles, are synergistic rather than merely additive when both stimuli act together. The second series of experiments was performed in the same manner as the first series, except that the right hindlimb of each rat was denervated 3 days before the experiment. Cellular DG uptakes were determined in soleus, plantaris, and gastrocnemius muscles of the left (sham) hindlimb, which was always resting, and in corresponding muscles of the right (denervated) limb, which was either resting or exercising. In the resting state, the denervated soleus muscle had normal basal DG uptake, but, unlike sham soleus muscle, did not respond to insulin stimulation. Denervated plantaris and gastrocnemius muscles exhibited 264% and 150% elevations in basal glucose uptake, respectively, compared with corresponding sham muscles. The latter two denervated muscles did respond to insulin, but the hormone-induced increments in DG uptake were 68% and 45%, respectively, lower than in corresponding contralateral sham muscles. Under basal conditions, exercise had no effect on DG uptake by the denervated soleus muscle, but increased uptake by denervated plantaris and gastrocnemius muscles 207% and 778%, respectively. Stimulation of exercising denervated muscles with exogenous insulin did not increase DG uptake by any muscle above the level observed with exercise alone. The results show that manifestations of insulin resistance in denervated muscles depend on muscle fiber population; denervated muscles, which still retain some ability to respond to insulin, increase DG uptake during exercise, whereas such an increase is absent in denervated muscles completely unresponsive to insulin; and exercise does not improve or restore the ability of denervated muscles to respond to insulin.

Dynamics of insulin resistance in denervated slow and fast muscles in vivo.

Sciatic nerve in one hindlimb of rats was sectioned, and animals were investigated 3, 6, 9, and 24 h and 3, 8, and 17 days after surgery. Cellular uptakes of 2-deoxy-D-glucose (DG) and alpha-aminoisobutyric acid (AIB) by soleus, plantaris, and gastrocnemius muscles of the denervated and contralateral sham hindlimb were compared in vivo. Effects of insulin on DG and AIB uptakes by soleus and plantaris muscles, but not gastrocnemius muscles, were reduced 20-58% as early as 3-6 h after denervation. Three to 17 days after denervation, soleus muscle did not respond to insulin stimulation of DG uptake, whereas plantaris and gastrocnemius muscles responded, but the insulin-induced increment in DG uptake was reduced 24-68% compared with the sham muscles. In contrast, none of the denervated muscles increased AIB uptake in response to insulin stimulation 3-17 days after surgery. The levels of creatine phosphate and ATP in calf muscles frozen in situ 3 days after denervation were increased 7 and 9%, respectively, and those of ADP, AMP, glucose-6-phosphate, and lactate were unchanged compared with sham muscles. It is concluded that muscle denervation results in a rapid development of insulin resistance, the effect of denervation depends on muscle fiber population, and insulin resistance of denervated muscles is not due to a cellular energy deficit.

Effects of sex and reproductive state on acoustic responsiveness in hamsters

—Semi-quantitative [ 14C]2-deoxyglucose (2DG) autoradiography was used to describe the responses of hamsters to 35 kHz mimics of the “ultrasoands” used for communication during mating. The first study examined the processing of ultrasoands and ambient noise by estrous females, some of which were deafened or hemideafened with plastic ear plugs. These data failed to reveal responses specific to the ultrasoands. However, lateralized responses to the ambient noise were apparent, especially in the hemideafened subjects. For the ventral cochlear nucleus (VCN), 2DG uptake was elevated contralateral to the plug and ipsilateral to the effective stimulus. In contrast, uptake by more rostral structures (dorsal n. of the lateral lemniscus=DNLL; ventral n. of the lateral lemniscus=VNLL; central n. of the inferior colliculus=CIC; medial geniculate n.) was elevated contralateral to the stimulus. A second experiment examined the responses of intact or castrated male and female hamsters to unilaterally presented ultrasoands and ambient noise. As before, relative levels of 2DG uptake differed across hemispheres for structures including the VCN, trapezoid body, VNLL, DNLL, and CIC. More surprisingly, intact females showed more 2DG uptake than males in the DNLL, auditory nerve, and lateral lemniscus. Females also tended to show elevated anterior hypothalamic uptake, but just in the hemisphere contralateral to the stimulus. These results suggest that male and female hamsters differ in acoustic responsiveness, and that this difference is mediated by hormonal effects at several brainstem components of the central auditory system.

Serum modulation of insulin action: effects on rat gingival fibroblast metabolism

Serum is reported to reduce the sensitivity of cells in culture to insulin. The effect of serum concentration in the growth medium on the responsiveness of control (C) and streptozotocin diabetic (D) rat gingival fibroblasts to insulin was measured by monitoring cellular DNA, RNA, total protein and medium hydroxyproline (collagen) levels, as well as the cellular uptake of C14-alpha-NH2-isobutyrate (alpha-AIB) and H3-2-deoxyglucose (2DG). The cells were grown in alpha-MEM at 5, 10, 15 or 20% FCS with 0, 10(-12), 10(-10), 10(-8) and 10(-6) M insulin used at each serum level. Insulin effects in the absence of serum were not assessed. For both the C and D rat cells, the DNA increased proportionately with increasing serum and insulin levels. In contrast, RNA and total cell protein increased with increase in insulin and decrease in serum, the magnitude of the effect being greater in C than in D cells. The insulin stimulation of both 2DG and alpha-AIB uptake and of collagen secretion varied inversely with serum concentrations. The magnitude of the insulin-serum interaction on metabolite uptake was greater for the D rat cells. These data indicate that serum significantly reduced the cell response to insulin stimulated metabolite uptake and collagen secretion, but was without apparent effect on the intracellular insulin responsive parameters. They suggest that serum factor(s) interfere with the availability of insulin to the cell and that the D rat cells are most affected.

Acoustic imprinting in guinea fowl chicks: age dependence of 2-deoxyglucose uptake in relevant forebrain areas

In 7-day-old guinea chicks play back of an imprinted acoustic stimulus was previously found to correlate with increased uptake of 2-deoxyglucose (2DG) in 3 rostral forebrain areas (HAD, LNH and MNH). Subdivisions of these areas defined by 2DG labelling may be association fields. Auditory areas did not show labelling differences between imprinted and control animals. In the present study imprinted guinea chicks of different age and with different experience were used in the 2DG experiments. Seven-day-old chicks (beyond the sensitive phase), 4-day-old (at the decline of sensitive phase) and 1- and 3-day-old chicks (within the sensitive phase) were given a 2DG injection and afterwards heard the stimulus to which they had been imprinted previously (1.8 kHz, 3 tone pips per s). While the typical labelling pattern was weak or absent in 1–4-day-old chicks the older animals consistently had high 2DG uptake in these areas. Unsuccessfully imprinted 7-day-old chicks, having all the behavioral test experience, showed no or weak labelling. These results are related to current literature on reticular activation of the relevant areas and on morphological changes there with termination of the sensitive phase. It is argued that the reticular activation of these areas, e.g. attention mechanisms are instrumental in securing imprinting success and that subsequent reorganization of the areas leads to stronger metabolic activation after the sensitive phase.

Effects of unilateral and bilateral cochlea removal on 2-deoxyglucose patterns in the chick auditory system.

The 2-deoxyglucose (2DG) method was used to map functional activity in the auditory system of chicks that had been subjected to unilateral or bilateral cochlea removal. Following survival times of 1 day to 4 weeks, chicks were exposed to continuous white noise in the 2DG experiments. In monaural subjects nucleus angularis and nucleus magnocellularis showed faint 2DG uptake on the side contralateral to the intact ear. In the binaural nucleus laminaris, the asymmetrical and almost mirror-imaged labeling pattern (Lippe, Stewart, and Rubel: Brain Res. 196:43-58, '80) was produced. The superior olive (OS) was strongly labeled on the ipsilateral side, whereas the contralateral OS showed only a slight 2DG uptake at its medial border. The lateral lemniscus and nucleus lemnisci lateralis, pars ventralis (LLv) showed stronger activation on the contralateral side. Both Nissl stains and 2DG patterns provide evidence that nucleus ventralis lemnisci lateralis (VLV) can be subdivided into an anterior (VLVa) and a posterior (VLVp) part. Whereas VLVp is labeled only contralaterally, VLVa is labeled on both sides with similar intensity. Nucleus mesencephalicus lateralis, pars dorsalis (MLD) is strongly labeled throughout contralaterally. The ipsilateral MLD shows a defined ventral portion of high 2DG uptake. Intensity of labeling here is symmetrical to the corresponding area of the contralateral MLD. These symmetrical patterns were related to the tonotopic organization of MLD, which was mapped in intact animals by using tone stimuli. Assuming that symmetrical 2DG uptake in monaural animals indicates excitatory input from both ears (EE-cells), it appears that these EE-cells occupy a sector of each isofrequency plane in MLD. Nucleus ovoidalis (Ov) generally was stronger labeled on the contralateral side. The columnar organization of field L as seen in monaural chicks has already been described (Scheich, Exp. Brain Res. 51:199-205, '83). In bilaterally deafened chicks, MLD, Ov, and layer L2 of field L showed strong but spatially restricted 2DG accumulation in contrast to absence of labeling in peripheral nuclei. The 2DG patterns in monaural chicks are likely to reflect excitatory input within the auditory system. In addition they reveal new insights into the functional organization of some of its nuclei. In particular, they support the notion that MLD contains maps of several interaural integration mechanisms similar to field L. Labeling in the auditory system of bilaterally deafened chicks may result from descending projections or from other than auditory inputs.

Single vibrissal cortical column in the mouse labeled with 2-deoxyglucose.

Columnar labeling was found in the primary somatosensory cortex of mice after stimulation of a single mystacial vibrissa following 2-deoxyglucose injection. The cortical vibrissal column had a cylindrical shape, passing through all layers of the cortex and was centered upon the appropriate vibrisal barrel. Columnar labeling extended beyond this barrel onto parts of neighbouring barrels, particularly within the same row. The densest labeling was found in layer IV in the barrel hollow. Removal of the non-stimulated vibrissae resulted in a subsequent lowering of 2DG uptake in the barrelfield surrounding the activated column, but did not affect the dimension of the activated column.

Focal ischemia of the rat brain: autoradiographic determination of cerebral glucose utilization, glucose content, and blood flow.

Focal cerebral ischemia was induced in rats by occlusion of the middle cerebral artery. By a triple-tracer technique, cerebral glucose utilization, glucose content, and blood flow were simultaneously determined. Computer-assisted autoradiography revealed a core of dense ischemia in the lateral two-thirds of the striatum. A border zone of increased 2-deoxy-D-glucose (DG) uptake surrounded the ischemic insult in the acute stage. The lumped constant was increased only moderately in the border zone. Therefore, the enhanced DG uptake reflected increased glucose consumption. CBF was reduced to 20-30% in the cortical border, while minor depression and in some animals hyperemia were evident in the striate border. Six hours after the insult, the border zones of increased glucose consumption had disappeared in half the animals. In no animals examined after 20 h was glucose consumption enhanced. The study indicated a stable metabolic response to a reproducible focal insult. We conclude that continued enhancement of glucose consumption in marginally perfused areas indicates neuronal damage.

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [ 14C]2-deoxyglucose study

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [ 14C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.

Functional metabolic mapping during forelimb movement in rat. I. Stimulation of motor cortex

The quantitative 14C-deoxyglucose (DG) autoradiographic technique has been used to study changes in cerebral metabolism during forelimb movements induced by graded stimulation of motor cortex. Experiments were directed at studying basic physiologic and anatomic aspects of the metabolic changes. Single shocks caused movement without metabolic change, whereas low-frequency trains caused seizures. Repetitive high-frequency train stimuli of short duration (500 Hz for 20 msec) caused jerk movements coupled with DG uptake in pathways. With stimulation of the forelimb motor zone at frequencies of 15-30/min there was prominent activation of cortical columns and strips in ipsilateral SI, SII, and MII, and contralateral MI and SI. Higher frequencies (120/min) were required to cause significant changes in DG in subcortical circuits. The most prominent changes occurred within a longitudinal corridor in dorsal thalamus and a ventral corridor in second-order sites in basal ganglia. Metabolic activation also occurred in contralateral cerebellum, the cuneate nucleus, and dorsal horn of the cervical spinal cord. Changes in these latter two sites were largely eliminated by removing feedback sensory activity. Stimulation of the forelimb sensory zone activated different sites in caudatoputamen and thalamus but similar zones in midbrain and cerebellum. The magnitude of the metabolic response in distant sites depended on the frequency of cortical stimulation. Different frequency-response relationships in different sites seemed to reflect the nature of the cortical input as well as differential effects of anesthesia. The pattern of the metabolic response was studied by comparing sites of activation with sites of the anatomic projections from motor and sensory cortical zones. 3H- and 14C-labeled amino acids were used to map the site and relative strength of pathways. Results revealed good correlation between the site of anatomic projection and the site of DG uptake but no consistent relationship between the relative strength of a projection and the magnitude of metabolic change within its field. Changes in glucose utilization with metabolic mapping experiments depend on the nature, strength, and frequency of stimulation; the site and nature of anatomic projection; the effects of anesthesia; and the strength of sensory feedback associated with the induced behavior.

Regional distribution of glucose utilization in the telencephalon of toads in response to configurational visual stimuli: a14C-2DG study

The regional glucose utilization in the telencephalon of toadsBufo bufo during stimulation with different visual key stimuli was quantitatively mapped by means of the14C-2DG autoradiographic method: (i) a 4×28 mm2 worm-like stripe (W) eliciting prey catching responses, (ii) a 84×84 mm2 square (S) releasing predator avoidance responses, and (iii) a 28×4 mm2 antiwormlike stripe (A) eliciting no motor response. Various telencephalic structures changed14C- 2DG uptake statistical significantly during stimulation with the above visual objects in comparison with binocular enucleated animals (brain-to-brain comparison) and in comparison between both hemispheres in monocular animals (interhemispherical comparison): (1) The ventral two-thirds of the posterior half of the medial palliumdecreased 14C-2DG uptake during W- and S-experiments, particularly in response to W. (2) In the posterior two-thirds of the lateral pallium,14C- 2DG uptake wasdecreased in response to the worm-, andincreased in response to the square (S) and antiworm stimuli (A). (3) The ventral striatumincreased uptake of14C-2DG during the animal's response to W- and S-stimuli significantly stronger than in the A-experiment. (4) The dorsal striatum also showed a significant change in14C-2DG uptake which, on a lower level, was not correlated with the type of stimulation experiment. Various prosencephalic structures are involved in circuitries related to attentional phenomena and the gating of prey catching and predator avoidance behavior. The different functions of these structures are discussed.