Local cerebral blood flow, local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.     

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 [14C]iodoantipyrine and 2-[14C]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.     

d-Amphetamine attenuates decreased cerebral glucose utilization after unilateral sensorimotor cortex contusion in rats

Unilateral contusion injury to the sensorimotor cortex causes, among other symptoms, a transient contralateral hindlimb hemiparesis in rats. A single i.p. 2 mg/kg dose of d-amphetamine (d-AMPH) 24 h after injury accelerates spontaneous recovery from this particular deficit. The mechanism(s) of spontaneous and d-AMPH enhanced recovery are unknown but alleviation of a neuronal depression has been proposed. This quantitative CMRglu study was designed to determine effects of cortical contusion injury and d-AMPH on CMRglu in cortical and subcortical structures. At 2 days after injury, CMRglu was significantly reduced compared to sham-operated controls only in structures ipsilateral to contusion. Affected structures included the caudate putamen, medial geniculate nucleus, lateral geniculate nucleus and the parietal cortex immediately posterior to injury. By 6 days post-contusion, the hypometabolism partially reversed in all structures. A single low dose of d-AMPH significantly alleviated the post-traumatic CMRglu reduction at 2 days after injury. Importantly, while this alleviation was not significant for any single structure, the main effect of treatment was highly significant. d-AMPH increased CMRglu at 2 days post-injury by 18-33% compared to contused/saline-treated rats. These results suggest that alleviation of neuronal metabolic depression may contribute to spontaneous and d-AMPH enhanced recovery.     

Effects of the self-administration of ethanol and ethanol/sucrose on rates of local cerebral glucose utilization in rats

In a previous study, the voluntary ingestion of ethanol by rats was found to be associated with a discrete pattern of changes in functional activity that included the nucleus accumbens, medial prefrontal cortex, basolateral and central nuclei of the amygdala, as well as the ventral midbrain. Rats in this study, however, consumed a combination of ethanol in a sucrose vehicle. The purpose of the present experiment was to characterize the role of sucrose in determining the effects of orally self-administered ethanol using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method for measurement of rates of local cerebral glucose utilization. A modified sucrose-substitution procedure was employed to train three groups of Wistar rats to self-administer either water, 10% ethanol (10E), or a 10% ethanol/2% sucrose solution (10E/2S) in daily sessions. An additional group of rats was trained using a modified acclimation procedure (home cage) in order to determine if any exposure to sucrose would alter rates of glucose utilization. Once stable rates of consumption were established, the 2DG method was applied immediately following completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g kg-1 on the day of the procedure or a comparable volume of water. Rates of energy metabolism were significantly increased in all three groups of rats that consumed ethanol (10E/2S, 10E, and home cage), as compared to rates in rats that consumed water. The areas of significant change included the rostral pole and posterior shell of the nucleus accumbens, medial prefrontal cortex, the basolateral and central nuclei of the amygdala, the ventral tegmental area, and the substantia nigra pars compacta. Thus, the pattern of changes in functional brain activity that accompanies voluntary ingestion of ethanol is independent of the vehicle in which the ethanol is presented or the procedures used to initiate consumption. Furthermore, these data demonstrate that it is the simultaneous activation of an interrelated network of limbic brain regions that serves as the substrate of the effects of ethanol self-administration.     

Glucose transporter expression in brain: relationship to cerebral glucose utilization

Glucose is the principle energy source for mammalian brain. Delivery of glucose from the blood to the brain requires its transport across the endothelial cells of the blood-brain barrier and across the plasma membranes of neurons and glia, which is mediated by the facilitative glucose transporter proteins. The two primary glucose transporter isoforms which function in cerebral glucose metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood-brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose transporter. The levels of expression of both transporters are regulated in concert with metabolic demand and regional rates of cerebral glucose utilization. We present several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. These include normal cerebral development in the rat, Alzheimer's disease, neuronal differentiation in vitro, and dehydration in the rat.     

Decreased insulin action on muscle glucose transport after eccentric contractions in rats

We have recently shown that eccentric contractions (Ecc) of rat calf muscles cause muscle damage and decreased glycogen and glucose transporter GLUT-4 protein content in the white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl. Physiol. 79: 1338-1345, 1995). To study whether these changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 microU/ml) 2 days after one-legged eccentric contractions of the calf muscles. Compared with control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG, whereas it was lower (P < 0.05) at both submaximal and maximal insulin concentrations in the Ecc-WG and at maximal concentrations in the Ecc-RG. In the Ecc-S, the glucose transport was unchanged in hindquarters perfused in the absence or presence of a submaximal stimulating concentration of insulin, whereas it was slightly (P < 0.05) higher during maximal insulin stimulation compared with control S. At the end of perfusion the glycogen concentrations were lower in both Ecc-gastrocnemius muscles compared with control muscles at all insulin concentrations. Fractional velocity of glycogen synthase increased similarly with increasing insulin concentrations in Ecc- and control WG and RG. We conclude that insulin action on glucose transport but not glycogen synthase activity is impaired in perfused muscle exposed to prior eccentric contractions.     

Non-insulin and non-exercise related increase of glucose utilization in rats and mice

The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta-guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D-glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates.     

FDG-PET in early infancy: simplified quantification methods to measure cerebral glucose utilization

For further insight into the physiology and pathogenesis of the developing brain, quantification of the cerebral glucose metabolism is needed. Arterial blood sampling or sampling of great volumes of blood is not justified for the purpose of PET studies in children. Therefore, we have developed simplified PET approaches to analyze brain FDG examinations during infancy. METHODS: The study consisted of 18 FDG-PET examinations chosen from our research protocols concerning hypoxicischemic encephalopathy and severe neonatal hypoglycemia. The input function for graphical analysis according to Patlak was derived in two ways: (1) a combined time-activity curve derived from the left ventricular activity concentration (first 7-17 min of the study) and radioactivity concentration in venous whole-blood samples and; (2) activity concentration measured in whole-blood venous blood samples (arterial plasma in one case). As an alternative for semiquantitation, the standardized uptake values (SUV) were calculated and correlated to local cerebral metabolic rates for glucose (LCMRGlc). RESULTS: The influx rate constants (Ki) and LCMRGlc values obtained using the combined curve versus venous curve did not differ statistically (p > 0.05). There was a good correlation between the SUV and LCMRGlc values (r = 0.83, p < 0.001). CONCLUSION: Local cerebral metabolic rates for glucose can be accurately calculated by using the combined curve (left ventricular activity concentration during first 5 min of the study and 2-3 venous whole-blood samples at the end of the study) for even the smallest pediatric patients. When blood samples cannot be obtained, SUV values provide an alternative for estimation of the cerebral glucose uptake and interindividual comparison of the patients.     

Local cerebral glucose utilization in the AS/AGU rat: a mutant with movement disorders

In order to examine the relative impairment of the diaphragm and other skeletal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined alterations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I expression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size averaged 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynamic measurements revealed a decrease in left ventricular peak systolic pressure of 19% (p < 0. 05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaphragm contractile properties was present in VD animals. For all animals combined, the reduction in diaphragm weight was related to infarct size (r = -0.74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alterations. IGF-I expression was increased by 55% in the diaphragm of rats with VD (p < 0.05). IGF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensatory mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude that systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not associated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.     

Decreased oral colonization of Streptococcus mutans during aging of Sprague-Dawley rats

The colonization by streptomycin-resistant Streptococcus mutans strains of the teeth of conventional and ex-germfree Sprague-Dawley rats of various ages fed either a high-sucrose or a high-glucose diet was studied. Bacterial colonization occurred with increasingly greater difficulty as the rats became older. This was observed in studies of the implantation of the test organism after oral inoculation with different cell numbers as well as its transmission between infected and uninfected rats. With rat fed sucrose diet, the effect of age could not be demonstrated until they were age 3 months or older; the results from rats fed a glucose diet suggest that changes may already have occurred early after weaning. Changes in susceptibility to colonization during aging manifested themselves as a decrease in the proportions of rats which became infected as well as lower population levels in infected rats. The possible mechanism(s) involved as well as the possible significance of the findings was discussed.     

Sex differences in regional cerebral glucose metabolism during a resting state

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.     

Leukocyte count and aggregation during the evolution of cerebral ischemic injury

We evaluated leukocyte aggregation by means of the leukergy test and count in 26 patients with atherothrombotic stroke and in 10 patients with transient ischemic attacks. The evaluation was performed within 24 h from the onset of symptoms and then repeated on day 2, 4, 6 and 8. Data were compared with those of 10 healthy controls. Stroke patients were followed until day 30 when a clinical examination and brain computed tomography were performed to evaluate the extent and outcome of cerebral damage. Both leukocyte aggregation and count were significantly increased in stroke patients with respect to controls. While leukocyte count was not able to differentiate the severity of neurological impairment in stroke patients, leukocyte aggregation was significantly higher in major than in minor stroke patients on days 2 and 4 (p < 0.05). Moreover, while values of leukocyte count recorded at entry remained substantially stable in the following determinations in all groups, leukocyte aggregation showed a significant increase (p < 0.05) on day 4 with respect to all the other determinations in major stroke patients. These findings show that the extent and temporal profile of changes in leukocyte count and aggregation are different in patients with cerebrovascular disease and suggest an involvement of altered leukocyte rheology in the development of cerebral ischemic injury.     

Intracerebroventricular administration of leptin markedly enhances insulin sensitivity and systemic glucose utilization in conscious rats

This study examines the acute, subacute (overnight), and chronic (7-day) effects of intracerebroventricular (i.c.v.) administration of r-metMuLeptin on insulin sensitivity and systemic glucose turnover in conscious unrestrained rats (body weight, 250 to 300 g). Under postabsorptive conditions, acute i.c.v. leptin ([AL] 10 microg bolus) did not affect tracer (3-(3)H-glucose)-determined glucose production (GP) and utilization (GU) rates during the 2-hour hyperinsulinemic (2 mU x kg(-1) x min(-1)) euglycemic clamp. Chronic i.c.v. leptin ([CL] 10 microg/d for 7 days) administered by osmotic pumps markedly reduced the daily food consumption (P < .05), body weight (P < .05), and postabsorptive basal plasma glucose level (P < .01). During the glucose clamp, GP was markedly suppressed (55%) with CL (P < .001 v vehicle and pair-fed control groups). The insulin-induced increment in GU was significantly greater with CL (23.3 +/- 1.8 mg(-1) x kg(-1) x min(-1)) than with vehicle (16.9 +/- 0.2) and pair-feeding (17.1 +/- 0.6, both P < .001). Subacute i.c.v. leptin ([SL] 10 microg bolus) moderately but insignificantly decreased overnight food consumption (-18%) and body weight (-2.5 +/- 1.5 g). The glucose infusion rate during the final 60 minutes of the glucose clamp was 43% greater than for the vehicle group (P < .0001). SL also significantly increased GU (P < .005) and suppressed GP (P < .05) during the glucose clamp. Thus, we conclude that i.c.v. administered leptin has strong actions on the central nervous system that result in significant increases in insulin sensitivity and systemic GU, and these effects are achieved as early as overnight after leptin administration.     

Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs

BACKGROUND: The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. METHODS: Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO2) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied. RESULTS: Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but not in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1.8 +/- 0.2 ml x min[-1] x 100 g[-1]) than with 28 degrees C (3.1 +/- 0.1 ml x min[-1] x 100 g[-1]; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degrees C animals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degrees C and remained significantly greater during reperfusion in the 34 degrees C and 37 degrees C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-100 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/- 0.9 microg/l) and 34 degrees C (3.5 +/- 0.5 microg/l) groups than the 31 degrees C (1.9 +/- 0.1 microg/l) and 28 degrees C (1.7 +/- 0.2 microg/l) animals. CONCLUSIONS: Hypothermia to 28 degrees C and 31 degrees C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28 degrees C compared with 31 degrees C. In contrast, ischemia during 34 degrees C and particularly 37 degrees C CPB showed greater EAA release and evidence of neurologic morbidity. Cooling to 31 degrees C was necessary to improve acute recovery during global cerebral ischemia on CPB.     

The effect of estradiol on carbohydrate utilization during prolonged exercise in rats

Female--castrated and male-sham operated rats were subjected to five hours of swimming. It was found that estradiol administered to female rats promotes a supercompensatory pattern of glycogen recovery in the myocardium at the end of the fifth hour of exercise. The hormone markedly delayed the glycogen mobilization from the liver during the first hour of swimming. Glycogen level in m. biceps femoris was essentially unchanged by estradiol both at rest and during exercise. Estradiol signifcantly increased glycogen level in m. masseter of resting rats. Hypoglycaemia developing at the end of the fifth hour of exercise was less pronounced in the estradiol--treated female rats than in the animals from other groups. It may be concluded that estradiol exerts a "sparing" effect on carbohydrate reserves during exercise in rats.     

Medial forebrain bundle lesions: Specific loss of feeding to decreased glucose utilization in rats.

Found that bilateral destruction of the medial forebrain bundle in female Sherman rats eliminated feeding to decreased intracellular glucose utilization (glucoprivation). The deficit was specific. Feeding was enhanced by dietary dilution and reduced by dietary concentration. More was eaten in the cold and less in the heat. The Ss were not differentially sensitive to quinine adulteration. They returned to normal body weight following regimens of gavage or of restricted feeding. Moreover, they did not differ from normal Ss in drinking to various thirst stimuli. It is suggested that the glucoprivic mechanism makes but a minor contribution to the initiation of spontaneous feeding. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spreading depression elicited by thermal effects of ultrasonic irradiation of cerebral cortex in rats

Dysbaric osteonecrosis is a major hazard to compressed air workers and an increasing hazard to divers. Symptomless osteonecrosis is best recognised by radiology and it is of fundamental importance that interpretation be reliable and accurate. There is much controversy concerning the significance of bone islands and cystic areas; several authors report bone islands and cystic areas to be up to eight times more frequent in compressed air workers and divers and believe that these represent positive evidence of osteonecrosis. Skeletal radiographs of 100 Royal Navy divers, all of whom were at risk to osteonecrosis were matched for age and rank with 100 controls, none of whom had been exposed to high pressures. The radiographs were interpreted by three radiologists working independently without knowing whether the radiographs were in the diving or control group. It is concluded that bone islands, cystic areas and sclerotic areas, as described in this text, occur with equal frequency in divers as in the normal population and do not represent positive evidence of osteonecrosis. The report includes autopsy studies of the proximal femur and proximal humerus in six diving fatalities. Five bone islands in the proximal humerus and one in the femoral neck were studied in bones removed from five divers. In the sixth case a cyst was seen to develop radiologically in the femoral neck and then reduce in size over 3 years and 10 months. Slab radiographs and histological section in all cases show no evidence of osteonecrosis.