Increases In Local Cerebral Glucose Utilization Research Articles

The A 1 receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?

It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A 1 receptor agonist R-N-phenylisopropyladenosine (R-Pia) injected prior to pilocarpine is able to reduce the uncoupling between LCGU and LCBF during status epilepticus (SE). Four groups of rats were studied: Saline, Pilo, R-Pia + Saline and R-Pia + Pilo. For LCGU and LCBF studies, rats were subjected to autoradiography using [ 14C]-2-deoxyglucose and [ 14C]-iodoantypirine, respectively. Radioligands were injected 4 h after SE onset. Neuronal loss was evaluated by Fluorojade-B (FJB) at two time points after SE onset (24 h and 7 days). The results showed a significant increase in LCGU in almost all brain regions studied in the Pilo and R-Pia + Pilo groups compared to controls. However, in R-Pia pretreated rats, the uncoupling between LCGU and LCBF was moderated in a limited number of structures as substantia nigra pars reticulata and hippocampal formation rather in favor of hyperperfusion. Significant increases in LCBF were observed in the entorhinal cortex, thalamic nuclei, mammillary body, red nucleus, zona incerta, pontine nucleus and visual cortex. The neuroprotective effect of R-Pia assessed by FJB showed a lower density of degenerating cells in the hippocampal formation, piriform cortex and basolateral amygdala. In conclusion our data shows that the neuroprotective effect of R-Pia was accompanied by a compensatory metabolic input in brain areas involved with seizures generation.

In vivo evidence for ligand-specific receptor activation in the central CRF system, as measured by local cerebral glucose utilization

Corticotropin-releasing factor (CRF) is well known for its role in the hypothalamic-pituitary-adrenocortical (HPA) axis and its involvement in stress and anxiety. CRF acts via two main receptor subtypes, CRF 1 and CRF 2. Other endogenous CRF-related peptide ligands are the Urocortins 1 and 2 and Stresscopin. While CRF is thought to mediate its anxiogenic-like properties through CRF 1, the role of CRF 2 and its endogenous ligands Urocortin 2 and Stresscopin are less clear, with a suggested role in mediating the delayed effects of stress. Measurement of local cerebral glucose utilization (LCGU) provides an estimate of neuronal activity, and is of potential use as a translational tool in comparison to FDG PET. We hypothesized that comparison of the patterns of metabolic changes induced by CRF-related peptides could provide further information on their role in the brain. The present studies examined the effects of CRF-related peptides on LCGU, and the role of CRF 1 and CRF 2 in the CRF-induced LCGU response. CRF induced increases in LCGU in hypothalamic, thalamic, cerebellar and hippocampal regions, and further studies using antagonists or mutant mice lacking a functional CRF 1 receptor clearly suggested a role for CRF 2 in this effect. Urocortin 1 increased LCGU in a dissected hindbrain region. However, central administration of the CRF 2-selective agonists Urocortin 2 and Stresscopin failed to affect LCGU, which may suggest ligand-dependent receptor activation within the CRF system. The present data supports a role for CRF 2 in the regulation of neuronal glucose metabolism.

Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain

The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7 ± 3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased LCGU. It is concluded that MCT1 transporters were up-regulated during chronic hyperglycemia at the level of brain substructures and independently of LCGU.

The Effect of Electrical Stimulation and Lesioning of the Anterior Thalamic Nucleus on Kainic Acid–Induced Focal Cortical Seizure Status in Rats

The present study aimed to clarify the effect of electrical stimulation and lesioning of the anterior nucleus of the thalamus (ANT) on kainic acid (KA)-induced focal cortical seizures in a rat model. To address the mechanism underlying these anticonvulsant actions, cerebral glucose metabolism after ANT electrical stimulation and lesioning was also examined. Wistar rats were divided into five major groups: control (n = 9), unilateral (n = 9), and bilateral (n = 9) ANT electrical stimulation, and unilateral (n = 9) and bilateral (n = 9) ANT lesioning. After KA injection, average clinical-seizure frequencies in each group were measured. Electrical stimulation of ANT was introduced after induction of seizure status epilepticus. Stimulation was on for 30 min and off for 30 min per 60-min cycle. Local cerebral glucose utilization (LCGU) was also measured by using [(14)C] 2-deoxyglucose autoradiography in three groups of rats: control (n = 7), bilateral ANT stimulation (n = 7), and bilateral ANT lesioning (n = 7). Unilateral ANT electrical stimulation and lesioning significantly reduced clinical seizure frequency, compared with control animals. Strikingly, no animals treated with bilateral ANT procedures demonstrated any clinical seizure. LCGU was markedly increased in the sensorimotor cortex, striatum, thalamus, mammillary body, and midbrain tegmentum of control group rats after KA injection, but no increase in LCGU was noted in rats treated with bilateral ANT lesioning or stimulation. The electrical stimulation and lesioning of ANT suppressed focal cortical clinical seizures induced by KA injection. Additionally, an analysis of cerebral metabolic changes indicated that these procedures might suppress the function as amplifier and synchronizer of seizure activity.

Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats

Ibogaine, a hallucinogenic indole alkaloid, has been proposed as a treatment for addiction to opioids and other drugs of abuse. The mechanism for its putative anti-addictive effects is unknown. In this study, the effects of ibogaine on local cerebral glucose utilization (LCGU) were determined in freely moving, drug-naive, or morphine-dependent adult, male, Sprague–Dawley rats using the [ 14C]2-deoxyglucose (2-DG) method. Morphine-dependent rats were treated with increasing doses of morphine (5–25 mg/kg, s.c., b.i.d.) and then maintained at 25 mg/kg (bid) for 4–7 days. For the 2-DG procedure, rats were injected with saline or ibogaine (40 mg/kg, i.p.). 2-DG was administered 1 h after administration of ibogaine. The rate of LCGU was determined by quantitative autoradiography in 46 brain regions. In drug-naive animals, ibogaine produced significant increases in LCGU in the parietal, cingulate, and occipital cortices and cerebellum compared to controls consistent with its activity as a hallucinogen and a tremorogen. Morphine-dependent rats had only minor alterations in LCGU at the time assessed in this experiment. However, in morphine-dependent animals, ibogaine produced a global decrease in LCGU that was greatest in brain regions such as the lateral and medial preoptic areas, nucleus of the diagonal band, nucleus accumbens shell, inferior colliculus, locus coeruleus, and flocculus compared to morphine-dependent animals treated with saline. These findings indicate that ibogaine produces distinctly different effects on LCGU in drug-naive and morphine-dependent rats. This suggests that different mechanisms may underlie ibogaine's hallucinogenic and anti-addictive effects.

RF加温後のラット正常脳における局所グルコース代謝の変化

The responsible mechanisms for hyperthermia-induced injury in the brain are not fully understood. The changes in glucose metabolism may play an important role in hyperthermia-induced injury. To elucidate these mechanisms, the changes in local cerebral glucose utilization (LCGU) was measured following the induction of localized interstitial hyperthermia using the [14C] -2-deoxy-D-glucose autoradiographic technique. The induction of hyperthermia was achieved by using 8MHz radiofrequency (RF) in rats. The range of hyperthermia is from 37 to 45°C for 30min. We found that (1) LCGU was significantly decreased in the lesions heated to 45°C ; (2) it was increased in the lesions heated to 43°C ; and (3) it was increased in the contralateral thalamus and hippocampus of a hyperthermia group. In conclusion, severe hyperthermia at 45°C caused irreversible cell damage as shown by a marked decrease in LCGU. Hyperthermia at 43°C caused neuronal shrinkage and an increase in LCGU. In comparison with our previous cerebral blood flow (CBF) study, increased LCGU occurred prior to the oneset of decreased CBF. These findings suggest that the increased LCGU around severely damaged lesions caused by hyperthermia may be manifested as cellular injury and the threshold temperature may be 43°C for 30min.

Local transport kinetics of glucose during acute and chronic nicotine infusion in rat brains.

Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (-10% to -20%) and in nearly all structures during chronic (-39% to -41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.

Alterations in local cerebral glucose utilization produced by D 3 dopamine receptor-selective doses of 7-OH-DPAT and nafadotride

The D 3 dopamine receptor, localized primarily in limbic brain areas, is a potential antipsychotic site. The effects of D 3 receptor stimulation or blockade on neuronal activity were determined using the [ 14 C] -2-deoxyglucose method. Freely-moving, adult, male, Sprague–Dawley rats were injected s.c. with saline, agonist 7-hydroxy-diphenylaminotetralin (7-OH-DPAT) (0.1 mg/kg), or antagonist l-nafadotride (1 mg/kg). These doses of 7-OH-DPAT and l-nafadotride are behaviorally active and are 10-fold lower than a dose producing significant in vivo occupancy of D 2 receptors. The [ 14 C] -2-deoxyglucose procedure was initiated 30 min after the administration of the test compound. The rate of local cerebral glucose utilization (LCGU) was determined by quantitative autoradiography. 7-OH-DPAT produced a significant increase in LCGU in the substantia nigra. l-Nafadotride produced significant increases in LCGU in several brain areas including the lateral preoptic area, lateral habenula, caudate, septal area, entorhinal cortex, and some thalamic and hypothalamic areas. These observations indicate that stimulation or blockade of D 3 receptors alters LCGU and that produces a unique pattern of alterations in LCGU suggestive of potential antipsychotic activity.

Hypothermia attenuates hyperglycolysis in the periphery of ischemic core in rat brain.

Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37+/-0.5 degrees C) and hypothermic (30+/-0.5 degrees C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.

Autoradiographic determination of local cerebral blood flow and local cerebral glucose utilization during chemical stimulation of the nucleus tractus solitarii of anesthetized rats

This study was conducted to determine whether the decrease in cerebral blood flow (CBF) observed during chemical stimulation of the nucleus tractus solitarius (NTS) can be explained by a decrease in cerebral metabolism. In anesthetized (urethane and chloralose), paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of l-glutamate. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were quantified in 43 brain structures by quantitative autoradiographic techniques using [ 14 C] iodoantipyrine and 2- [ 14 C] deoxyglucose, respectively. During chemical stimulation of the NTS ( n=6), LCBF decreased significantly in 32 of the 43 structures investigated when compared to either a control group with artificial cerebrospinal fluid injection ( n=6), or a controlled hemorrhage group ( n=5). In the controlled hemorrhage group, blood pressure was decreased to a degree comparable to that induced by microinjection of l-glutamate into the NTS. Mean blood flow of all structures investigated was significantly ( P<0.01) lower in the stimulation group than that in the control group and in the hemorrhage group. No significant differences in LCGU were observed between the three investigated groups in all structures examined except for an increase in LCGU in the chemically stimulated NTS site. It is concluded that the decrease in LCBF measured in most brain structures during chemical stimulation of the NTS is not caused by a decrease in LCGU in these structures and may therefore be explained by neurogenic influences on brain vessels.

Increase of glucose transporter densities (Glut1 and Glut3) during chronic administration of nicotine in rat brain

Chronic infusion of nicotine is known to result in a distinct pattern of increases in local cerebral glucose utilization (LCGU). The present study addresses the question whether this increase in LCGU is paralleled by (1) a local increase in Glut1 and/or Glut3 glucose transporter densities and (2) a local increase in capillary density in the brain. Nicotine was infused by osmotic minipumps for one week. In cryosections of rat brains local densities of Glut1 (vascular) and Glut3 (neuronal) glucose transporters were measured by immunoautoradiographic methods whereas local capillary densities were determined by an immunofluorescent method. Densities of glucose transporters Glut1 and Glut3 were increased in 12 of the 27 structures investigated. Glut1 was elevated in four additional structures and Glut3 in two more structures. Comparison of the changes in transporter densities with the changes of LCGU measured in a previous study during chronic nicotine infusion showed that LCGU was also elevated in most of these structures. In contrast, capillary density remained unchanged in all structures investigated. It is concluded that one week of nicotine infusion is sufficient to raise the densities of Glut1 and Glut3 glucose transporters predominantly in those structures in which LCGU is elevated. The unchanged capillary density under these conditions indicates an increased density of Glut1 transporters per capillary.

The changes of LCGU and rCBF in the MCA occlusion-recirculation model in rats and the ameliorating effect of MCI-186, a novel free radical scavenger.

We examined the change of regional cerebral blood flow (rCBF) and local cerebral glucose utilization (LCGU) in the middle cerebral artery (MCA) occlusion or recirculation model of rats, and tested anti-ischemic effects of a free radical scavenger, 3-methyl-1-phenyl-pyrazolon-5-one (MCI-186). A remarkable increase in LCGU was observed in the cortex supplied by the anterior cerebral artery after recirculation. This hypermetabolism of glucose was at least partly caused by the postischemic oxidative injury, since MCI-186 ameliorated the high LCGU in this area. These results suggested the usefulness of this type of free radical scavenger for inhibiting the postischemic injury.

Alterations of local cerebral glucose utilization in lean and obese fa/ fa rats after acute adrenalectomy

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/ fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/ fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong or be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/ fa rat. It is suggested that the long-term hypercorticism of obese fa/ fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/ fa rats and contribute to the expression of the obese phenotype.

Local cerebral blood flow and glucose utilization after blood exchange with a hemoglobin-based O2 carrier in conscious rats.

The effects of a blood exchange on cerebral blood flow and glucose utilization were studied. A near to total blood exchange (hematocrit < 3%) was achieved in conscious rats by isovolemic hemodilution. Ultrapurified, polymerized, bovine hemoglobin (UPBHB) served as a blood substitute. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures of conscious rats by means of the ido[14C]antipyrine and the 2-[14C]-deoxy-D-glucose methods. A group of rats without blood exchange served as control. After blood exchange LCBF increased from 36 to 126% in the different brain structures resulting in a nearly doubled mean cerebral blood flow (+82%). LCGU increased only moderately by 0-24%. Significant increases in LCGU were observed in 16 brain structures. Mean cerebral glucose utilization slightly increased (+14%). The relationship between LCGU and LCBF was found to be tight both in the control group (r = 0.95) as well as after blood replacement (r = 0.94), although it was reset to a higher overall LCBF-to-LCGU ratio. The profound increases in LCBF observed after blood exchange, which were not paralleled by comparable increases in LCGU, might be explained by a reduction of blood viscosity after blood exchange. Additional effects of blood exchange observed in the present study were an increase of mean arterial blood pressure and a decline of heart rate. The results indicate that replacement of blood with the hemoglobin-based oxygen carrier UPBHB appears to meet the cerebral circulatory and metabolic demands of the brain tissue.

Tetrahydroaminoacridine and Physostigmine Increase Cerebral Glucose Utilization in Specific Cortical and Subcortical Regions in the Rat

The effects of the anticholinesterases tetrahydroaminoacridine (THA) and physostigmine on local cerebral glucose utilization (LCGU) were studied in the conscious rat, using the autoradiographic [14C]deoxyglucose technique. THA (5 mg/kg i.p.) increased LCGU significantly in 8 of the 43 regions studied. A higher dose of THA (10 mg/kg) produced a metabolic activation in 19 of the 43 regions. LCGU increased in cortical areas (including parietal and temporal cortices), the septohippocampal system, the thalamus, the lateral habenula, the basolateral amygdala, the superior colliculus, and the substantia nigra. Scopolamine (4 mg/kg i.p.) reversed the THA-induced LCGU increase. Physostigmine (0.2 and 0.5 mg/kg) increased LCGU in 15 and 22 regions, respectively. The average magnitude of the change induced by 0.5 mg/kg of physostigmine was similar to that observed after THA at 10 mg/kg, but the topography of the effects was somewhat different. Physostigmine increased LCGU in the preoptic magnocellular area, the brainstem, and the cerebellum but not in the parietal cortex. The effects in the septohippocampal system were smaller than those induced by THA. The regional topography of the LCGU increase overlapped the distribution of the M2 muscarinic receptors and that of acetylcholinesterase activity. These data suggest that the major effects of THA and physostigmine on LCGU result from their anticholinesterase action.

Rolling mouse Nagoya as a mutant animal model of basal ganglia dysfunction: determination of absolute rates of local cerebral glucose utilization

In order to elucidate the neuronal mechanism of the motor disturbances of the Rolling mouse Nagoya (rolling), a neurological mutant mouse (genotype rol/rol) showing frequent lurching and falling over on walking, we determined absolute rates of local cerebral glucose utilization (LCGU) with the [ 14C]deoxyglucose method. The rates were compared with those of heterozygote (+/ rol) with normal behavior, and of normal mice (+/+) of the same strain (C3Hf/Nga). Rolling showed marked and significant increases in LCGU in the structures of the basal ganglia such as the globus pallidus, entopeduncular nucleus, substantia nigra pars compacta and pars reticulata, and subthalamic nucleus, comfirming our previous finding with semiquantitative LCGU determination. Additional significant but much less marked increases in LCGU of rolling were found in some structures of the brainstem and limbic system, such as the pedunculopontine nucleus, red nucleus, ventral tegmental area, lateral habenula, and CA1 and CA3 of the hippocampus. Although rolling has been regarded as an animal model of cerebellar ataxia, rolling showed no alterations of LCGU in the cerebellum. The heterozygote showed intermediate increases in LCGU between rolling and normal mice in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. Our findings indicate that rolling has a definite, genetically determined dysfunction of the basal ganglia. The primary site of the basal ganglia dysfunction might probably be in the striatum, involving both the neostriatum and limbic striatum, and resulting in secondary dysfunction in their target structures.

Effects of 1,3-di- o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain

The 2-deoxy- d-[1- 14C]glucose ([ 14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di- o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [ 14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n, basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticula. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands 13, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.

82 CHANGES IN BRAIN GLUCOSE UTILIZATION INDUCED BY ACUTE HYPOXIA DURING DEVELOPMENT

Changes in regional glucose utilization might be involved in neuronal damage due to hypoxia. The quantitative autoradiographic 2-14C-deoxyglucose technique (2DG) was applied to the measurement of the effects of an acute hypoxic exposure on local cerebral glucose utilization (LCGU) in the 10 (P10), 14 (P14), and 21 (P21) day-old rat. The animals were exposed to the hypoxic (7% O2/93% N2) or control gas mixture (21% O2/79% N2) for 20 min before the initiation and for 45 min of the 2DG procedure. At P10, the exposure to the hypoxic gas mixture induced a generalized increased in LCGU which affected 40 structures (including white matter) of the 45 studied. At P14, LCGU increased in 5 areas and decreased in 11 regions, mainly brainstem and respiratory areas in hypoxic as compared to control rats. But average cerebral glucose utilization was similar in both groups. Finally, at P21, LCGU decreased in 11 structures of hypoxic rats as compared to controls. The increase in LCGU of the hypoxic 10 day-old rat is likely to be the reflection of the stimulation of anaerobic glycolysis in brain structures with a low metabolic rate. Conversely, at P14 and P21, metabolic rate increases and the brain becomes more dependent upon oxygen. These results suggest that immature brain responds to an acute hypoxic aggression in a specific way according to the maturation of oxidative metabolic pathways.

Effects of dorsal raphe stimulation on cerebral glucose utilization in the anaesthetized rat

The aim of this study was to determine the effects of electrical stimulation of the dorsal raphe nucleus on local cerebral glucose utilization (LCGU) in the α-chloralose anaesthetized rat. Activation of the dorsal raphe nucleus effected significant increases in LCGU, ranging from 13 to 52% in 8 brain structures out of 33 investigated. Increases were restricted to extrapyramidal and limbic non-specific areas, and no modifications were observed in cortical areas. The comparison with our previous results, showing that a similar raphe activation induced a global decrease in local cerebral blood flow, suggests that the ascending serotonergic system may be of importance in the regulation of the cerebral circulation.

HA1077, a novel calcium antagonistic antivasospasm drug, increases both cerebral blood flow and glucose metabolism in conscious rats

The effects of a novel calcium antagonistic antivasospasm drug, HA1077, on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were studied in 33 anatomically discrete regions of the brain in conscious rats, using the quantitative autoradiographic [ 14C]iodoantipyrine and [ 14C]2-deoxyglucose techniques. HA1077 was infused i.v. over a 30-min period (1 or 3 mg/kg). HA1077 significantly increased LCBF in 9 of 33 sites in rats given 1 mg/kg, and in 14 of 33 sites in rats given 3 mg/kg compared to the control group given vehicle. Significant increases in LCGU were also noted in 16 of 33 sites in rats given 3 mg/kg. HA1077 increased both cerebral blood flow and glucose metabolism in conscious rats.