Increases In Local Cerebral Glucose Utilization Research Articles

Preischemic Administration of Flunarizine or Phencyclidine Reduces Local Cerebral Glucose Utilization in Rat Hippocampus Seven Days after Ischemia

The purpose of the present study was to investigate the influence of ischemia on postischemic metabolic activity of the brain. Furthermore, the effect of preischemic application of neuroprotective agents such as flunarizine or phencyclidine on postischemic local cerebral glucose utilization (LCGU) was examined. Forebrain ischemia in the rat was performed for 10 min with bilateral carotid clamping, administration of trimethaphan and blood withdrawal to obtain a mean arterial blood pressure of 40 mm Hg. LCGU was determined 7 days after ischemia by injecting 14C-deoxy-D-glucose in saline solution. A significant increase in LCGU in the CA1 subfield of the hippocampus was found 7 days after ischemia, whereas preischemic administration of flunarizine or phencyclidine inhibited this increase. Alterations in LCGU of other brain regions were insignificant.

Local cerebral glucose utilization in normoxemic and hypoxemic newborn lambs

To determine if hypoxemia altered local cerebral glucose utilization (LCGU) in newborn lambs, and where these alterations occurred, we measured LCGU using the 2-[ 14C]deoxyglucose ([ 14C]D-autoradiographic technique in lambs made hypoxemic by gradual reduction in inspired oxygen concentration. In 5 normoxemic control lambs, aged 3 days, LCGU of the cerebral cortex and white matter was higher than published values of LCGU in similar structures in near term normal fetuses and 2–4 times higher than reported values in normoxemic puppies. LCGU was highest in vestibular nuclei and auditory structures, followed by cerebellar nuclei, cerebral subcortical structures, and white matter. In 6 hypoxemic newborn lambs ( p a O 2 14–18 torr) consistent increases in LCGU were noted only in the corona radiata compared to the values obtained in the normoxemic control lambs (36.5 ± 8.1 vs. 23.9 ± 1.7 μmol/100 per min, mean ± S.D., P < 0.02). This increase in LCGU in white matter was clearly noted in autoradiographs in which thin dark central regions within white matter often reached high into the gyri. In the hypoxic group, LCGU of the corona radiata superseded the value in many gray matter structures. In addition, patchy increases of [ 14C]DG utilization were present in the cerebral cortex of two hypoxemic lambs. Acute hypoxemia increases glucose utilization of the corona radiata to values equivalent to many gray matter structures, and leads to heterogeneous glucose metabolism in the cerebral cortex, but does not alter LCGU in other gray matter structures of newborn sheep.

Postichemic glucose utilization in rat hippocampal layers

The influence on hippocampal glucose utilization was determined in male Wistar rats 7 days after a 10-min forebrain ischemia. Ischemia was induced by clamping of the carotid arteries and lowering blood pressure to 40 mm Hg. Despite severe neuronal damage as assessed by histological techniques, local cerebral glucose utilization (LCGU) was significantly increased in the pyramidal and radiatum layer of the CA1 sector, while in layers of the CA2, CA3 and CA4 sector and dentate gyrus, LCGU was reduced compared to non-ischemic controls. The increases in LCGU are suggested to reflect long-lasting hyperexcitation in the selectively vulnerable CA1 sector, implicating a correlation between cellular hypermetabolism and neuronal damage.

Morphine-induced alterations of local cerebral glucose utilization in the basal ganglia of rats

The actions of various doses of morphine on the local cerebral glucose utilization (LCGU) were studied by means of the autoradiographic [ 14C]2-deoxyglucose technique. Morphine (1–15 mg/kg i.p.) decreased LCGU in most areas of the basal ganglia (caudate nucleus, globus pallidus, nucleus accumbens), but not in the substantia nigra pars compacta. LCGU was also decreased in limbic nuclei, such as septum, hippocampus and amygdala, and in most thalamic areas. In most cortical regions, a decrease was found as well. Findings in some efferent nuclei seemed of particular interest, namely in the substantia nigra pars reticulata, anteroventral and lateral nucleus of the thalamus and the subthalamic nucleus, where decrease in LCGU were found after administration of 7.5 mg/kg or sometimes lower doses, but not after 15 mg/kg of morphine. The decreases seem to reflect a general depressory effect of morphine on neuronal activity which is known from electrophysiological studies. Part of these effects might be, in addition, due to an activation of dopaminergic neurons, since dopamine mainly acts as an inhibitory neurotransmitter. This dopaminergic activation leads to characteristic behavioral effects after lower doses of morphine. The largest dose used (15 mg/kg) produces muscular rigidity, probably by a direct action on the striatum. This effect antagonizes and masks the dopaminomimetic effects. The results suggest that it also antagonizes the functional alterations in some efferent nuclei of the basal ganglia manifest after lower doses of morphine. Local injections of morphine (15 μg) led to decreases of LCGU in the various parts of the striatum, but to increases in lateral and anteroventral thalamus. These increases in LCGU in two thalamic areas seem to support the above hypothesis that the rigidity is accompanied, at least in part of the efferent nuclei of the basal ganglia, by increases in LCGU antagonizing the inhibitory effects described above.

The effects of melatonin and pinealectomy upon local cerebral glucose utilization in awake unrestrained rats are restricted to a few specific regions

The effects of the infusion of melatonin (MT) and/or of pinealectomy upon glucose utilization in anatomically discrete regions of the brain of freely moving rats have been studied by the qauntitative autoradiographic 2-deoxy- d-[1- 14C]glucose technique. The experiments were made from 14.00 to 16.00 h, when MT is normally not secreted by the pineal gland, in order to compare the local cerebral glucose utilization (LCGU) response to MT from animals with long-term (pinealectomized) or short-term (pineal intact) absence of MT secretion. The majority of the 98 brain areas examined showed no change in LCGU after MT administration and/or pinealectomy. Pinealectomy increased the LCGU in the median mammillary nucleus only, whereas following MT administration, an increase in LCGU was observed in 3 cerebral regions of intact rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexus of the third ventricle) and in 5 cerebral regions of pinealectomized rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexuses of the lateral ventricles, third and fourth ventricles). Except for the choroid plexuses of the fourth ventricle, there was no difference in LCGU response to MT between pinealectomized and intact animals. This does not favor the hypothesis of receptor supersentitivity under the conditions of this experiment. Our results suggest that the hypothalamus, nucleus of the solitary tract and choroid plexuses represent a neural substrate through which MT could influence the activity of the central nervous system when administered at alow a dose under near-physiological conditions.

The nucleus locus coeruleus modulates local cerebral glucose utilization during noise stress in rats

Local cerebral glucose utilization (LCGU), estimated by the quantitative autoradiographic 2-deoxyglucose technique, was studied in rats with bilateral 6-hydroxydopamine lesions of the locus coeruleus (LC) and in vehicle-injected controls. Unanesthetized animals were studied during exposure to stressful levels of white noise (95 dB) or in relative silence (50 dB). Results indicated that noise caused greater and more widespread increases in LCGU in animals with LC lesions than in vehicle-injected controls. Lesions alone had little or no effect in animals not subjected to noise. Analyses of variance revealed significant treatment interaction effects (intact/lesion × silence/noise) for 37 of 109 regions measured. The pattern of results suggests that the LC acts during stress to limit unnecessary cerebral activity that might interfere with efficient sensory processing and/or the organization of appropriate behavioral response. In this respect LC function may be similar to those actions of the peripheral sympathetic nervous system that suppress vegetative functions during stress to allow for the performance of coping responses.

Hypermetabolic state following experimental head injury.

Local cerebral glucose utilization (LCGU) was studied in 35 conscious rats after a fluid percussion injury (cerebral contusion). The experiments were divided into two parts. (I) Natural course: LCGU was quantitatively measured in 17 rats by the 14C-deoxyglucose autoradiographic method (Sokoloff et al. 1977) at 1, 2, 4 and 24 hours after injury. Sham operation was made in six rats. (II) DC-potential and LCGU: LCGU was studied with DC-potential and EEG monitoring in 12 rats. Results were as follows: (I) i) Glucose uptake was reduced at the center of the contusion in all cases. ii) Two different effects were observed in LCGU change two hours after injury: normal or slight increase in four of six rats (type A) and a remarkable increase in the cortex of the injured hemisphere in two of six rats (type B). iii) The pattern of increase in LCGU (type B) resembles that of cortical spreading depression. (II) i) Negative shift of DC-potential concomitant with EEG suppression in the injured hemisphere was observed frequently one to two hours after injury. ii) The increased LCGU pattern during DC-potential negative shift was identical with that of type B. iii) LCGU pattern without DC-potential change resembles that of type A. We concluded that the hypermetabolism occurring in the damaged cortex was due to a spreading depression. The findings obtained here should yield very important information concerning pathogenesis and treatment of human head injury.

Effects of nicotine on local cerebral glucose utilization in the rat

We used the autoradiographic 2-deoxy-D-[1-14C]glucose (14C-DG) method of Sokoloff to identify brain areas with altered rates of local cerebral glucose utilization (LCGU) in vivo in response to peripheral I-nicotine administration (0.1, 0.3, 1.0, and 1.75 mg/kg, s.c.). Nicotine stimulated LCGU primarily in areas reported to contain nicotine binding sites, indicating that the sites are true receptors. Increases in LCGU of 100% or more over control were obtained in the medial habenula, fasciculus retroflexus, superior colliculus, and median eminence. Substantial stimulation (50-100% increases) also was obtained in the cerebellar vermis, interpeduncular nucleus, and anteroventral and interanteromedial thalamic nuclei. Moderate increases (20-50%) were observed in the reticular nucleus of the medulla, paramedian lobule, nucleus of the spinal tract of the trigeminal nerve, presubiculum, subiculum, red nucleus, ventral tegmental area, substantia nigra, nucleus ambiguus, nucleus tractus solitarius, dorsal lateral geniculate nucleus, mammillothalamic tract, and fornix. The greatest stimulation in most affected areas was obtained with 0.3 mg/kg nicotine administered at 2 min, but not longer, before 14C-DG. Effects of nicotine on LCGU were antagonized by mecamylamine. The findings indicate that the interaction of nicotine with specific binding sites is coupled to cerebral energy metabolism. The distribution of in vivo cerebral metabolic effects of nicotine implicates various brain regions in the behavioral and physiological effects of nicotine.

Metabolic activation of intercortical and corticothalamic pathways during enflurane anesthesia in rats.

The purpose of this study was to examine the effects of enflurane on local cerebral glucose utilization (LCGU), and to provide further insight into the mechanism of the epileptogenic properties of enflurane. Twenty-four male Wistar rats were divided into four groups; three groups with intact cortex received 0.5, 2, or 4% enflurane, and one group with unilateral cortex excised received 4% enflurane. LCGU was measured at each anesthetic concentration using the autoradiographic 2-[14C]deoxyglucose method. LCGU in ten of 33 structures examined during 2% enflurane decreased by 19-33%, and LCGU in 22 structures during 4% enflurane decreased by 19-65%, when compared with that during 0.5% enflurane. While LCGU, in most structures, decreased in a dose-related manner, LCGU in the corpus callosum, thalamic ventrobasal complex, and hippocampal CA3 field during 4% enflurane increased by 31-70%, compared with that during 0.5% and/or 2% enflurane. With unilateral cortical excision during 4% enflurane, the increase in LCGU in the ventrobasal complex was obliterated in the excision side, and the increase in the corpus callosum was attenuated. High LCGU in the hippocampal CA3 field and contralateral ventrobasal complex was not affected with cortical excision. These results indicate that intercortical and corticothalamic pathways are metabolically activated during deep enflurane anesthesia, suggesting that the epileptogenic property of enflurane is related to activation of these pathways.

Alterations in local cerebral glucose utilization during electrical stimulation of the striatum and globus pallidus in rats

Alterations in local cerebral glucose utilization (LCGU) in conscious rats during stimulation of the striatum and the globus pallidus were investigated using the [ 14C]deoxyglucose method. Stimulation of the globus pallidus produced a marked contraversive circling behavior, while stimulation of the striatum led only to contraversive head turning. Unilateral stimulation of the striatum increased LCGU bilaterally in the globus pallidus and substantia nigra pars compacta, but only ipsilaterally in the entopeduncular nucleus, substantia nigra pars reticulata and subthalamic nucleus. Similar stimulation of the globus pallidus increased LCGU in the globus pallidus, substantia nigra pars reticulata and compacta, entopeduncular nucleus, subthalamic nucleus, lateral habenular nucleus, parafascicular nucleus of the thalamus, deep layers of the superior colliculus and pedunculopontine nucleus, exclusively on the ipsilateral side. These results indicate that the electrical stimulation induces LCGU changes in the respective structures having both monosynaptic and transsynaptic neuronal inputs. Some changes may also be mediated by antidromic activation. They also suggest that activation of a synaptic process whether excitatory or inhibitory results in increases in LCGU. The bilateral modulatory effects of striatal stimulation may cancel out the circling behavior seen during pallidal stimulation, and cause only head turning.

Changes in local cerebral glucose utilization associated with the spontaneous ovulatory surge of luteinizing hormone in the rat.

Brain activity during the spontaneous ovulatory surge of luteinizing hormone (LH) has been studied by measuring local cerebral glucose utilization (LCGU) by the [14C]-2-deoxyglucose method. The LCGU was determined in 37 brain areas and the pituitary gland in conscious, freely moving female rats in the morning and the late afternoon of proestrus. No increases in LCGU were detected, but, unexpectedly, there was a significant decrease in the LCGU measured in the afternoon compared with the morning of proestrus in the medial preoptic and anterior hypothalamic areas, the arcuate nucleus, median eminence and amygdala. Significant reductions in LCGU also occurred in the midbrain central grey and reticular formation. These results suggest that the LH and/or the prolactin surge is associated with a significant reduction in the activity of brain areas known to be essential components of the central control of gonadotropin and prolactin secretion. In the case of the arcuate nucleus and median eminence, for example, the results could be explained by a decreased activity of the opioid and dopaminergic neurons which are known to inhibit the release of luteinizing hormone releasing hormone (LHRH). Disinhibition of LHRH neurons would result in the increased release of LHRH into the hypophysial portal vessels. Reduction in the activity of the arcuate dopamine neurons could also play a major role in the prolactin surge. The decreased LCGU of the midbrain central grey may be related to the onset of lordosis behavior which appears to be time-locked to the LH surge.

Alterations in local cerebral glucose utilization induced by phencyclidine

The effects of phencyclidine (PCP; 0.5, 1.5, 10 mg/kg, i.v.) on local cerebral glucose utilization (LCGU) in the rat were studied with the 2-deoxy- d-[1- 14C]glucose method. Significant findings were obtained in 41 of 87 brain regions of PCP-treated rats (25–270% of control). Rates of LCGU increased throughout the limbic system, except the habenula. Although LCGU increased in most sensory structures, it decreased in specific layers of the somatosensory and auditory cortices and the inferior collicules. Evidence was seen for dissociation between LCGU responses of specific thalamic relay areas and their terminal fields in the cortex. Increases in LCGU occurred th throughout the motor system, manifesting a striking pattern of columnar activity in the motor cortex. However, LCGU was reduced in the frontal cortical pole. Elevated LCGU was onserved in the pontine nuclei and the nucleus solitarius. Effects of 5 mg/kg PCP diminished with time although 8 regions maintained a metabolic alteration at 180 min. PCP induced several behaviors, including stereotypes, which varied with the dose and time after drug administration. The results demonstrate a PCP-induced activation of various functional circuits in the brain, especially the limbic system, and may provide a physiological basis for PCP's psychotomimetic p properties.

Altered local cerebral glucose utilization induced by electrical stimulations of the thalamic sensory and parafascicular nuclei in rats

Alterations in local cerebral glucose utilization (LCGU) induced by electrical stimulation of the sensory relay nucleus (VPL) or parafascicular nucleus (Pf) of the thalamus in conscious rats were measured by the [ 14C]2-deoxyglucose method, the objective being to assess the mechanism of analgesia induced by electrical stimulations of these structures. Stimulation of the VPL induced an ipsilateral increase in LCGU in the sensory thalamic nucleus itself, the sensory cortex and substantia nigra. Stimulation of the Pf induced bilateral increases in LCGU in the Pf and central medial nucleus of the thalamus, sensory cortex, ventral areas of the striatum and substantia nigra, and ipsilateral increase in LCGU in the periaqueductal gray, parabrachial pontine nucleus and deep layers of the superior colliculus. No significant change in LCGU was detected in the raphe dorsalis, raphe magnus and spinal dorsal horn, in both groups. Our observations coincide with clinical findings that unilateral electrical stimulation of the Pf leads to amelioration of intractable pain bilaterally, while that of the VPL induces an analgesia restricted to the contralateral side.

Changes in local cerebral glucose utilization induced by the beta- carbolines FG 7142 and DMCM reveal brain structures involved in the control of anxiety and seizure activity

The brain regions that may be functionally involved in the control of anxiety and the development of seizures were examined using quantitative 1-14C-deoxyglucose autoradiography. For this purpose, beta-carbolines FG 7142 and DMCM were employed. They exert their effects via the benzodiazepine receptor, and whereas both possess anxiogenic properties, FG 7142 is a proconvulsant and DMCM a potent convulsant. The pattern of increases of local cerebral glucose utilization (LCGU) induced by FG 7142 was mainly restricted to limbic structures, such as the lateral septal nucleus, the anterior thalamic nuclei, and the mamillary nuclei. However, structures involved in motor regulation were also affected. A pronounced increase in LCGU was observed in the posterior part of the substantia nigra, pars reticulata. Further, the LCGU of the globus pallidus, the ventral thalamic nucleus, and the cerebellum was increased. DMCM likewise increased LCGU of the mamillary body and the lateral septal nucleus. In contrast to FG 7142, the hippocampal formation displayed an increase in LCGU, while LCGU of the anterior thalamic nuclei was unchanged. A pronounced increase in LCGU was seen in the substantia nigra, pars reticulata in addition to other structures functionally involved in central motor regulation. The specific benzodiazepine antagonist Ro 15-1788 antagonized the effects of both FG 7142 and DMCM. It is concluded that the beta-carbolines FG 7142 and DMCM produce selective effects upon LCGU that are mediated by benzodiazepine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of isoflurane anesthesia on local cerebral glucose utilization in the rat.

The effect of isoflurane anesthesia on local rate of glucose utilization was investigated in the rat brain by means of the autoradiographic 14C-2-deoxyglucose method. Local cerebral glucose utilization (LCGU) was measured in 26 neuroanatomic structures of awake and isoflurane-anesthetized rats. Isoflurane anesthesia (1.5% inspired) caused both increases and decreases in LCGU. Significant reductions were found in all cortical areas examined and in primary sensory relay nuclei of central visual and auditory pathways. Among regions of the extrapyramidal motor system, LCGU was increased in substantia nigra pars compacta, and decreased in cerebellum, red nucleus, and ventral thalamus. Large increases in LCGU were observed in some structures of the limbic system such as the medial habenulo-interpeduncular system and the CA3 field of hippocampus. LCGU was significantly reduced by isoflurane in the CA1-CA2 field and dentate gyrus of hippocampus. These results are similar to previous findings on the LCGU response to other inhaled and intravenous anesthetics and further confirm the regional specificity of the effects of anesthetics on brain metabolism.

Effects of σ agonist compounds on local cerebral glucose utilization: relationship to psychotomimetic properties

The effects of 3, structurally unrelated sigma agonist compounds on local cerebral glucose utilization (LCGU) were compared. The common effects of σ agonist compounds on LCGU included a moderate, global elevation of LCGU. Superimposed upon this elevation were larger increases in LCGU occuring mainly in components of the limbic system, and the pyramidal and extrapyramidal motor systems. The only structures whose metabolic rates were significantly elevated by all 3 compounds were the frontal cortex and the anterior cingulate cortex. The altered metabolic activity in these limbic brain regions may underly the psychotomimetic effects produced by σ agonist compounds.

Arecoline-induced elevations of regional cerebral metabolism in the conscious rat

Local cerebral glucose utilization (LCGU) was measured, using the quantitative ([ 14C]2-deoxy- d-glucose ([ 14C]DG) method, at 3 min after administration to 3-month-old, awake Fischer rats of the muscarinic agonist arecoline (AREC) 0.05, 0.5, 5, 15 or 50 mg/kg or saline i.p. Animals were pretreated with methylatropine (a cholinergic antagonist which does not enter the brain and has no effect on cerebral metabolism) 4 mg/kg s.c. to prevent parasympathomimetic side-effects of AREC. Tremor produced by AREC was rated subjectively. Intensity of tremor was dose-related, peaked at 2–5 min after AREC, and abated within 30 min. Elevations in LCGU (measured after [ 14C]DG injection during peak behavior) in extrapyramidal regions, which mediate tremor, were related to the intensity of tremor. The lowest dose of AREC selectively increased LCGU in the hippocampus and median raphe; higher doses produced more generalized metabolic enhancement. In the hippocampus and cortex, LCGU rose in layers in which cholinoceptive cells are located. Regions of the auditory pathway and superficial neocortical layers (I–II) were generally unaffected by AREC, but LCGU did not decrease in any region. The selective increase in LCGU produced by low doses of AREC in the hippocampus presumably is due to a specific action of AREC, and demonstrates the high sensitivity of this region to cholinomimetic stimulation.

Local cerebral glucose utilization altered in rats with unilateral electrolytic striatal lesions and modification by apomorphine

Alterations in local cerebral glucose utilization (LCGU) in rats with unilateral striatal lesions and the modification by apomorphine were investigated. Electrolytic lesions were made in the rostral part of the right striatum, and 1, 7, and 30 days later, LCGU was observed in terms of relative and absolute LCGU values, using the [ 14C]deoxyglucose method. A definite change in the pattern of LCGU was seen only at 7 days. These were increases in LCGU in the globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata, and decreases in the ventroanterior-ventrolateral (VAL) and ventromedial (VM) thalamic nuclei and lateral habenula, all on the lesioned side. The circling behavior following the lesion, however, was maximal after 2 days and disappeared after 7 days. Intravenous administration of apomorphine (1.5 mg/kg) produced different modifications in the LCGU pattern between the intact and lesioned sides, at 7 days after producing the lesions. On the intact side, there were increases in LCGU in the striatum, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata and subthalamic nucleus, and a decrease in the lateral habenula. No such changes were observed on the lesioned side. These results indicate firstly that electrolytic striatal lesions induce LCGU increases or decreases in the structures which receive the striatal input, secondly that the mechanism of this change differs from that of the circling behavior seen in case of striatal lesions, and finally that the majority of the LCGU changes in the basal ganglia and thalamus following intravenous administration of apomorphine are brought about by an altered input of neuronal activity from the striatum to these structures.

THE EFFECTS OF HYPOXEMIA AND HYPOTENSION ON LOCAL CEREBRAL GLUCOSE UTILIZATION IN THE AWAKE NEWBORN PUPPY

As part of an ongoing study to evaluate the pathogenesis of neonatal hypoxic-ischemic brain injury, we have studied the effect of hypoxemia and severe hypotension on newborn brain metabolism. In 5 puppies, severe hypoxemia was produced by having the puppy breath a 4% O2/96% N2 mixture; normal MAP was maintained. In 7, severe hypotension (MAP 20-25 mmHg) was induced by hemorrhage; these animals spontaneously hyperventilated and maintained normal or elevated pO2. During these insults, local cerebral glucose utilization (LCGU) was studied using quantitative autoradiography and 14C-deoxyglucose. Hypoxemia caused a marked increase in LCGU to all brain structures: increases of 200-300% occurred diffusely in cerebral cortex and subcortical nuclei; increases of 300-600% occurred in white matter. Severe hypotension caused localized increases in LCGU: increases of 300-500% were seen in parasagittal cerebrum; increases of 150-200% were seen in the subependymal zone. The distribution of the increased LCGU correlated with the presumed distribution of pathologic injury after both insults; i.e. diffuse neuronal necrosis after hypoxemia and watershed infarction after severe hypotension. The increased LCGU probably represents a pathologic disruption of oxidative metabolism. The resultant increase in local tissue lactate may further injure brain elements locally. Thus, increased LOGU may be both a marker of the most vulnerable brain regions after insult and also an important step in the pathogenesis of neonatal hypoxic ischemic brain injury.

Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

We sought to determine whether the increases in local cerebral blood flow (LBCF) elicited by focal electrical stimulation within the dorsal medullary reticular formation (DMRF), are secondary to or independent of, increased local cerebral glucose utilization (LCGU). Rats were anesthetized (chloralose), paralyzed, artificially ventilated and arterial pressure and blood gases controlled. LCBF and LCGU were determined in two separate groups of animals, using the autoradiographic [ 14C]iodoantipyrine and [ 14C]2-deoxyglucose methods, respectively. In unstimulated controls, LCBF (n= 5) and LCGU (n= 5) were linearly related (r = 0.780; P < 0.001) in the 27 brain regions studied. During DMRF stimulation LCGU increased significantly in 21 of the 27 regions, including cerebral cortex (up to 168% of control), thalamic nuclei (up to 161%) and selected ponto-medullary regions (e.g. parabrachial complex: 212%; vestibular complex: 147%). Along with LCGU, LCBF rose significantly in 25 regions (sensory motor cortex: 163%; anterior thalamus: 161%; parabrachial complex: 186%). Correlation analysis demonstrated that, during DMRF stimulation, the close relationship between LCBF and LCGU is preserved (r = 0.845; P < 0.001) and that, in addition, the increase in LCBF (δ LCBF) is proportional to the increase in LCGU (δ LCGU) (δLCGU+ 6.92; r = 0.7729; P < 0.001). Excitation of neurons or fibers within DMRF increases brain metabolism globally and blood flow secondarily. The DMRF appears to modulate cerebral metabolism globally, by as yet undefined pathways.