Regional cerebral blood flow and glucose utilization during hyperinsulinemia

Regional cerebral blood flow and glucose utilization were measured in awake-restrained rats during euglycemic hyperinsulinemia and were found to be normal. This indicates that elevated plasma insulin does not alter cerebral blood flow and cannot explain decreases in cerebral blood flow measured during acute hyperglycemia.     

Pentoxifylline: cerebral blood flow and glucose utilization in conscious spontaneously hypertensive rats

Pentoxifylline, 0.30 mg/kg/min, significantly reduced cerebral blood flow by 10-44% in 19 of 23 regions studied in conscious spontaneously hypertensive rats. Bilateral ligation of the common carotid arteries reduced cerebral blood flow to 24-46% of resting values in 20 structures; a further reduction to 10-27% of resting values was seen after pentoxifylline in 10 cortical or subcortical structures. Thus, in conscious hypertensive rats, there is no evidence that pentoxifylline redistributes blood flow from normal to low flow brain regions. Pentoxifylline did not reduce the metabolic rate of glucose.     

Effects of glycerol on local cerebral glucose utilization and local cerebral blood flow of hypoxic rats

Effects of a continuous infusion of glycerol on the hypoxic rat were assessed by measurements of local cerebral glucose utilization and local cerebral blood flow using the quantitative autoradiographic 1-[C-14]-2-deoxyglucose and [C-14]-iodoantipyrine techniques, respectively. Local cerebral glucose utilization of the hypoxic rat was decreased in most of cerebral structures except for the amygdala, septal nucleus and the white matter. Local cerebral glucose utilization of the hypoxic rat treated with glycerol was recovered to the pattern of normal control, although glucose utilization of the nucleus raphe and locus ceruleus was accelerated. Cerebral blood flow of the hypoxic rat was elevated in almost of all measured structures. In particular, blood flow in the substantia nigra and locus ceruleus was increased significantly. The pattern of local cerebral blood flow of the hypoxic rat treated with glycerol was more analogous to that of normal control than of hypoxic rat without treatment. It is suggested that glycerol has beneficial effects by elevating local cerebral glucose utilization inhibited and decreasing local cerebral blood flow overshot on the hypoxic condition.     

Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein

We have used quantitative autoradiographic techniques to study the relationship between cerebral blood flow (CBF) and glucose utilization (CGU) in two lines of transgenic mice overexpressing Swedish mutant amyloid precursor protein (APP) and APP-derived Abeta peptides. Mice were studied at an age when there are no amyloid plaques. In the 2123 line, CBF was reduced only in telencephalic regions with no corresponding decrease in CGU. In 2576 transgenics, a line with higher levels of Abeta peptide, both CBF and CGU were reduced throughout the brain. The data indicate that Abeta induces alterations in resting CBF that are either associated with or independent of alterations in CGU and that occur in the absence of amyloid deposition in neuropil of blood vessels. These observations support the hypothesis that cerebrovascular and metabolic abnormalities are early events in the pathogenesis of Alzheimer's disease.     

鼠侧向液压脑损伤后脑血流量和葡萄糖利用率的改变

目的：探讨液压冲击脑损伤后脑血流量（ＣＢＦ），局部脑血流量（ｒＣＢＦ）与局部葡萄糖利用率（ｒＣＧＵ）的变化及其对神经元继发性损伤的影响。方法：应用激光多普勒流量计和定量放射自显影技术。结果：液压冲击脑损伤导致６０秒内ＣＢＦ短暂升高然后显著下降，且持续６０分钟低于正常，同侧和对侧大脑半球的ＣＢＦ相应降为正常值的７９％和９３％。外伤后１小时，损伤侧脑皮层，丘脑及海马的ｒＣＢＦ下降１２％～５９％，对侧大脑半球相应区域则下降１０％～４０％。相反，ｒＣＧＵ在冲击区周围脑皮质及同侧丘脑和海马区升高２７％～１０１％，在对侧大脑半球相应区域则升高２０％～９１％，海马区由液压冲击引起的ｒＣＢＦ和ｒＣＧＵ分离性变化十分显著，同侧海马ＣＡ１和ＣＡ２－３区存活的神经元数量在损伤后两星期时显著减少。结论：ｒＣＢＦ和ｒＣＧＵ的分离性变化是引起外伤后神经元尤其是海马区神经元继发损伤的主要因素。     

Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task

To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.     

Effect of dexamethasone on tumorous brain edema--changes in regional cerebral blood flow and glucose utilization

An experimental brain tumor was produced by implanting a piece of A.A. ascites tumor into the parietal brain of rat. Local cerebral blood flow (LCBF) and glucose utilization (LCGU) were determined in this model with 14C-iodoantipyrine and 14C-deoxyglucose quantitative autoradiographic methods, respectively, to investigate the change of blood flow and glucose metabolism and the effect of dexamethasone in the brain with tumor. LCBF and LCGU in the peritumoral brain tissue were reduced 75% and 60%, respectively, compared with the values of the control. In the ipsilateral frontal and occipital cortical areas far from the tumor, 50% and 45% reduction of LCBF, respectively, was observed. More than 30% reduction of LCGU was seen in the same areas. In the caudate and corpus callosum ipsilateral to the tumor, LCBF was diminished 25% and 40%, respectively. LCGU was not significantly changed in these areas. No significant changes of LCBF and LCGU were observed in the contralateral hemisphere. In the dexamethasone-treated animal, the reduction of LCBF was less in all areas where it was reduced in the untreated animal. In the peritumoral brain tissue, LCBF was significantly higher compared to that of the untreated group, and 80% of the normal level. In the ipsilateral frontal and occipital cortical areas, caudate and corpus callosum, LCBF was about the same as that of the control group. In the animal treated with dexamethasone, quantitative analysis of LCGU could not be made because of high glucose levels in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in saccharin-induced cerebral glucose utilization between obesity-prone and -resistant rats

Approximately half the male Sprague-Dawley rats fed a high energy diet develop diet-induced obesity (DIO). The remainder are diet-resistant (DR) and do not become obese. Resistance to DIO can be predicted before exposure to high energy diets by the presence of diminished norepinephrine (NE) release to an intravenous glucose load. Here chow-fed rats were prospectively placed in DR- or DIO-prone 'diet groups' by the areas under their glucose-induced (1 g/kg, i.v.) NE curves (DR rats less than 1200 pg/ml/60 min; DIO rats greater than 4500 pg/ml/60 min). To test the central pathways involved in the response to the intake of palatable foods, rats were first trained to drink 1 ml of 50% glucose within 1 min and then were tested for local cerebral glucose utilization using uptake of [14C]2-deoxy-D-glucose ([14C]2-DG) after receiving 0.15% sodium saccharin in place of glucose to avoid altering plasma glucose levels. Controls for basal cerebral metabolism (C) received no solution. DR-prone rats increased [14C]2-DG uptake by 60-190% in autonomic areas of the medulla (nucleus tractus solitarius, area postrema, dorsal motor nucleus X) and amygdala (central nucleus) in the S versus C conditions while DIO-prone rats had high basal levels of [14C]2-DG uptake in these areas and showed no increase after S. Also, DR-prone rats had 9-25% higher [14C]2-DG uptake in the ventromedial hypothalamic nucleus than DIO rats regardless of C or S conditions. Thus, pre-existing differences in the activation of autonomic areas of the brain in response to a food-related cue may be of etiological significance in the different patterns of food intake and weight gain seen in DR- and DIO-prone rats fed a high energy diet.     

Triple-tracer autoradiography of cerebral blood flow, glucose utilization, and protein synthesis in rat brain

A triple-tracer autoradiographic technique is described that permits the simultaneous measurement of cerebral blood flow, glucose consumption, and protein synthesis using 131I-iodoantipyrine (131I-IAP), [14C]deoxyglucose ([14C]DG), and 3H-amino acids as radioactive tracers. Autoradiographic differentiation between isotopes was performed by taking advantage of different half-lives, solubility of labeled tracers in a wash solution, and sensitivity of the photographic material to disintegrations of the radionuclides. Blood flow autoradiograms using 131I-IAP were obtained by immediate exposure of brain sections to Kodak NMB film for 24 h. During 131I autoradiography contamination by 3H was absent and by 14C was negligible at tissue concentrations of less than 0.45 microCi/g brain tissue. After complete decay of 131I, reexposure of brain sections to Kodak NMB film for 2 weeks provided autoradiograms that stemmed exclusively from 14C disintegrations without contamination by either 131I or 3H and that represented regional glucose utilization. Brain sections were then wash-incubated for 12 h to remove [14C]DG, [14C]DG-6-phosphate, and free 3H-amino acids from the tissue, and exposed to 3H-sensitive LKB Ultrofilm for 2 weeks for autoradiography of 3H-amino acid incorporation into proteins. 14C radioactivity remaining in the tissue section after wash-incubation was determined by exposing sections again for 2 weeks to Kodak NMB film; the resulting contribution to the blackening of 3H-autoradiograms was corrected for by means of digital subtraction using an image-processing system. The triple-tracer autoradiographic technique was validated in rats under various physiological and pathophysiological conditions. In intact animals extinction correction was necessary only for 3H-autoradiograms. Under pathophysiological conditions, however, significant contamination of 131I by 14C occurred in regions with low blood flow and increased glucose utilization rate; this also required correction by digital subtraction. The interpretation of triple-tracer autoradiographic results is limited by the same restrictions as single-tracer autoradiography, but the simultaneous assessment of the three parameters considerably facilitates the interpretation of the flow/metabolic relationship, particularly under pathological conditions.     

Sphenopalatine ganglion stimulation increases regional cerebral blood flow independent of glucose utilization in the cat

Regional cerebral blood flow was determined using the tracer [14C]iodoantipyrine and regional brain dissection, and regional cerebral glucose utilization determined using the 2-deoxyglucose method, in the alpha-chloralose-anesthetized cat to evaluate the effect of electrical stimulation of the sphenopalatine (pterygopalatine) ganglion. Unilateral stimulation for either a short period (7-10 min) or a longer period (45 min) resulted in increases in blood flow in the ipsilateral cerebral cortex of up to 45% (parietal cortex) with, in addition, increased flow in the white matter of the corpus callosum (42%). The flow changes for both brief and prolonged stimulation were not significantly different. Flow was not altered in either the brainstem or basal ganglia (caudate nucleus). In contrast to these changes in cerebral blood flow no changes in cerebral glucose utilization were seen in any of the brain areas studied and in particular there were no changes in the areas in which blood flow increased. These data provide clear evidence that the innervation of the cerebral vasculature from the main parasympathetic ganglion can alter cerebral blood flow independent of cerebral metabolism.     

Differences in quinpirole-induced local cerebral glucose utilization between naive and sensitized rats

Dopaminergic psychostimulants produce behavioral responses of greater magnitude with repeated, intermittent administration, than a single, acute dose, a phenomenon known as ‘sensitization’. Alterations in regional neuronal activity produced by quinpirole, a D₂/D₃ agonist, in quinpirole-naive and quinpirole-sensitized rats were assessed on the basis of local cerebral glucose utilization (LCGU) using the [¹⁴C]2-deoxyglucose (2-DG) method. Adult, male Long-Evans rats (180–200 g, n=7–9/group) were subjected to ten injections of quinpirole (0.5 mg/kg, s.c.) administered every 3rd day; controls and quinpirole-naive rats received saline. Locomotor activity was quantitated after injections one and ten to confirm sensitization. The 2-DG procedure was initiated 60 min after an 11th injection in freely moving rats. LCGU was determined in 43 brain regions by quantitative autoradiography. In quinpirole-naive rats, quinpirole decreased LCGU in the caudate/putamen (84% of control), lateral habenula (80% of control), and motor cortex (79% of control). In sensitized rats, quinpirole decreased LCGU in the nucleus accumbens core and shell (77 and 83% of control, respectively) and ventral pallidum (82% of control) as well as in the caudate/putamen (86% of control), lateral habenula (77% of control), and motor cortex (79% of control). This suggests that decreased neuronal activity in the nucleus accumbens and ventral pallidum may underlie the augmented behavioral response to quinpirole in sensitized animals.     

Influence of gamma-hydroxybutyrate on the relationship between local cerebral glucose utilization and local cerebral blood flow in the rat brain

The relationship between local cerebral glucose utilization (LCGU) and local CBF (LCBF) was examined during the action of gamma-hydroxybutyrate (GHB) (900 mg/kg i.v.) in conscious rats. GHB induced discrepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed (-51%), whereas global blood flow was not significantly altered. The marked dissociation between the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased.     

Persistent hypertension does not alter the cerebral blood flow and glucose utilization in young-adult Dahl salt-sensitive rats

The Dahl- Iwai salt-sensitive (DS) rat develops hypertension due to a high-salt diet without any structural alterations of the brain arteries and arterioles. We investigated the effect of persistent hypertension on the regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) in the DS rats. The rats were fed either a high-salt diet (HSD; 8% NaCl, n = 5) or a low-salt diet (LSD; 0.3% NaCl, n = 6) from 8 to 16 weeks of age, and the HSD group developed hypertension lasting for 1 month. At 16 weeks of age, the rCBF was measured in the sensorimotor and visual cortices using the hydrogen clearance method, and the rCGU was measured in 26 different brain structures using the [(14)C]deoxyglucose method. The mean arterial pressure was significantly higher in the HSD group (168+/-7 mm Hg) than in the LSD group (139+/-3 mm Hg) (P < 0.01). The mean rCBF and the rCGU values tended to be lower in the HSD group than in the LSD group; however, there were no statistically significant differences except for the reduced rCGU value in the nucleus accumbens. These results suggest that hypertension itself does not alter either the rCBF or the rCGU in young-adult DS rats. This indicates that the functional / structural changes of the cerebral arteries and arterioles that are associated with hypertension appear to be responsible for altered rCBF and rCGU in other animal models of hypertension.     

Triple-tracer autoradiography demonstrates effects of hyperglycemia on cerebral blood flow, pH, and glucose utilization in cerebral ischemia of rats

Triple-tracer autoradiography was used to measure topographic changes in local cerebral blood flow, cerebral tissue pH, and local cerebral glucose utilization in hyperglycemic and normoglycemic rats, all of which had undergone occlusion of the middle cerebral artery. More severe and extensive reduction of all three variables was observed in the hyperglycemic than in the normoglycemic rats. In seven normoglycemic rats, significant reduction in local cerebral blood flow (p less than 0.025) was observed in the ischemic but not in the contralateral nonischemic side at the lateral portion of the caudate nucleus and the neocortex. Tissue pH was significantly lower (p less than 0.025) only at the lateral portion of the caudate nucleus in the ischemic side. No significant differences in local cerebral glucose utilization were observed when the two hemispheres were compared. In the ischemic hemisphere of five hyperglycemic rats, the caudate nucleus and the neocortex exhibited significant reduction (p less than 0.025) in local cerebral blood flow, tissue pH, and local cerebral glucose utilization. Even in the nonischemic hemisphere of the hyperglycemic rats, local cerebral blood flow in the caudate nucleus and the neocortex was significantly reduced (p less than 0.025) compared with the normoglycemic rats. No significant change in tissue pH or local cerebral glucose utilization was observed throughout the nonischemic hemisphere of the hyperglycemic compared with the normoglycemic rats. Tissue pH was systematically lower in the hyperglycemic than in the normoglycemic rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.     

Persistent vegetative state with high cerebral blood flow following profound hypoglycemia

A persistent vegetative state (severe dementia) developed in a 30-year-old man following hypoglycemic coma. Despite the poor clinical outcome, sensory evoked response recovered between 6 and 34 months after the insult. The cerebral blood flow level at rest after 34 months was slightly above the normal range. This finding contrasts with the low cerebral blood flow regularly reported in patients who are comatose or stuporous following severe brain hypoxia-ischemia.     

Correlation of local cerebral blood flow, glucose utilization, and tissue pH following a middle cerebral artery occlusion in the rat

The use of three sets of the double-tracer autoradiographic technique to measure topographical changes of local cerebral blood flow (LCBF), glucose utilization (LCGU), and tissue pH following a 3 h middle cerebral artery (MCA) occlusion in the rat is described. In a sham-operated group of animals there was 10% reduction of LCBF and 7% reduction of LCGU in the most affected areas as compared to the contralateral homologous regions. However, the ratio of LCGU/LCBF in the affected areas remained within normal limits. In the MCA-occluded animals, LCGU showed a bimodal response to decreased LCBF. LCGU decreased with reduced LCBF until LCBF fell to 38% of normal. Below this LCBF level LCGU increased, most likely implying anerobic glycolysis. Decline of tissue pH corresponds to the mismatch of LCBF and LCGU. These results suggest that brain tissue pH change cannot be predicted on the basis of LCBF or LCGU alone.     

Differences in regional cerebral blood flow during musical and verbal hallucinations

A 51-year-old male patient suffered from both musical and verbal hallucinations with insight. We performed three single photon emission computed tomographic scans with the patient in different conditions: baseline without hallucinations, musical hallucinations, and verbal hallucinations. Clearly, different patterns of regional cerebral blood flow (rCBF) were observed during musical and verbal hallucinations. The findings suggest that musical and verbal hallucinations are associated with different patterns of rCBF, possibly reflecting the different causes of the two types of hallucinations.