bluuebunny/crossref_metadata_2025 huggingface dataset:
Confounded Correlations: Statistical Limitations in the Analysis of Interregional Relationships of Cerebral Metabolic Activity
Authors: Ford Ian
Published: April 2011

Various statistical approaches have been applied to tomographic determinations of glucose utilization putatively to gain insight into functional interrelationships in the brain. An approach based on the use of a partial correlation coefficient has been proposed to eliminate the distorting influence of systematic interpatient differences in glucose utilization. It is shown, by examination of explicit statistical models, that this form of analysis does not permit unambiguous conclusions to be drawn.
Cerebral Intracellular ADP Concentrations during Hypercarbia: An in vivo 31P Nuclear Magnetic Resonance Study in Rats
Authors: Litt Lawrence , González-Méndez Ricardo , Severinghaus John W. , Hamilton William K. , Rampil Ira J. , Shuleshko Julia , Murphy-Boesch Joseph , James Thomas L.
Published: April 2011

Qualitatively different responses of ADP levels have previously been observed in the brain during hypercarbia. One investigation has found that cerebral ADP stayed constant during hypercarbia in rats that were anesthetized with halothane, while another observed that ADP decreased during supercarbia in rats that received no supplemental anesthesia. This article reports an in vivo 31P nuclear magnetic resonance study to test the hypothesis that halothane anesthesia accounts for the discrepant observations. Isoflurane anesthesia was also studied in a second group of rats to see if a different general anesthetic agent would cause the same effects that halothane causes. The two groups of five rats underwent dual episodes of hypercarbia that were separated by a 45-min recovery period. General anesthesia, either 0.5% halothane or 1.0% isoflurane, was administered during the first episode but not during the second. Hypercarbia during halothane anesthesia caused the measured phosphocreatine (PCr) to decrease by 40%, while the calculated change in ADP was 10%, in agreement with the former investigation. In contrast, hypercarbia during either isoflurane anesthesia or no anesthesia caused a decrease of only 10% in PCr, which meant that the calculated decrease in ADP was 60%, in agreement with the results of the second investigation. We conclude that during hypercarbia, clinical concentrations of halothane, unlike clinical concentrations of isoflurane, interfere with the regulation of ATP metabolism.
Cerebral Vascular Resistance following Platelet and Leukocyte Removal from Perfusate
Authors: Kintner D. B. , Kranner P. W. , Gilboe D. D.
Published: April 2011

The rapid increases in cerebral vascular resistance (CVR) frequently observed during extracorporeal perfusion of isolated organs with whole or diluted blood have been investigated using the isolated canine brain preparation. Our data strongly suggest that these increases are caused by a vasoconstrictor that is present in the buffy coat. Plasma serotonin levels were measured and found to be insignificant after conditioning and storage. Conditioning the blood reduced the platelets and the potential for thromboxane A2 production to ∼40% of normal. However, there was no correlation between thromboxane B2 levels and increases in CVR. Removal of the buffy coat effectively removed all of the leukocytes. Thus, one of the leukotrienes may have been responsible for the buffy coat-induced vasoconstriction.
Brain Metabolic Correlates of Hypoxic-Ischemic Cerebral Necrosis in Mid-Gestational Sheep Fetuses: Significance of Hypotension
Authors: Wagner Kenneth R. , Ting Pauline , Westfall Margaret V. , Yamaguchi Shun-Ichi , Bacher John D. , Myers Ronald E.
Published: April 2011

Midgestational sheep fetuses exposed to marked hypoxia for 2 h remain brain intact if MABP is maintained above 30 mm Hg. On the other hand, similarly hypoxic fetuses, if they experience reductions in MABP below 30 mm Hg, develop foci of necrosis that predominantly affect hemispheric white matter and neostriatum. Cortex damage is more restricted and is usually associated with more massive underlying white matter damage. The present study examines the brain metabolic basis for the important role of hypotension in brain injury development in marked hypoxia. Sheep fetuses rendered hypoxic by respiring their ewes with 11% oxygen (fetal Pao2 = 8–12 mm Hg) in which MABP was maintained above 30 mm Hg showed increases in brain lactic acid concentrations to 7–13 μmol/g but unaltered energy charge. In contrast, fetuses that sustained MABP reductions below 30 mm Hg showed increases in lactic acid concentrations in vulnerable structures to 16–24 μmol/g accompanied by marked decreases in energy charge. The vulnerable structures also showed reductions in fructose concentrations but a variable behavior of other brain metabolites including phosphocreatine, glycogen, and glucose. Thus, the present findings suggest a relation between hypotension during marked hypoxia, low energy charge, lactic acid accumulation in brain at high concentrations, and fetal brain injury. The ewes of hypoxic hypotensive fetuses received pentobarbital at lower doses than did those of fetuses that maintained blood pressure. This suggests that pentobarbital plays an important role in protecting the fetal brain from asphyxia by extending the hypoxic fetus's ability to maintain blood pressure in addition to reducing its brain metabolism.
Brain Organization in Schizophrenia
Authors: Volkow Nora D. , Brodie Jonathan D. , Wolf Alfred P. , Gomez-Mont Francisco , Cancro Robert , Van Gelder Peter , Russell Jerome A. G. , Overall John
Published: April 2011

Brain metabolism was measured with positron emission tomography and [11C]deoxyglucose during baseline and during a visual task in 12 normal subjects and 18 schizophrenic patients. Global measures of metabolism for 11 brain regions were transformed into relative values by dividing them by the metabolic value for whole brain. Factor analysis was accomplished on the matrix of intercorrelations among the relative regional values for the normal and for the schizophrenic patients under baseline and under the task. Four factors that revealed independently varying metabolism in frontal, occipital, left-versus-right hemisphere, and subcortical structures were obtained. The frontal and subcortical factors discriminated between normal subjects and schizophrenic patients, whereas the occipital factor discriminated between baseline and task. Although activity in these individual regions varied significantly, it was the pattern of differences in regional metabolic activity that best discriminated between diagnostic groups and testing conditions.
Intracellular Brain pH, Indicator Tissue Perfusion, Electroencephalography, and Histology in Severe and Moderate Focal Cortical Ischemia in the Rabbit
Authors: Meyer Fredric B. , Anderson Robert E. , Sundt Thoralf M. , Yaksh Tony L.
Published: April 2011

Intracellular brain pH and indicator tissue perfusion were measured with a lipid-soluble, pH-sensitive fluorescent indicator in 10 rabbits who had either severe or moderate focal ischemia depending on whether the middle cerebral artery was occluded at its main trunk or bifurcation. Preocclusion tissue indicator perfusion was 50.1 ml/100 g/min and intracellular brain pH was 7.03. In severe focal ischemia, immediate postocclusion tissue perfusion was 12.7 ml/100 g/min and intracellular brain pH was 6.64. Four hours after occlusion, the perfusion was 5.2 ml/100 g/min and intracellular brain pH was 6.08. There was EEG and histological confirmation of infarction. In the moderate focal ischemia group, immediate postocclusion flow was 20.0 ml/100 g/min and intracellular brain pH was 6.92. At 3 h, postocclusion tissue perfusion was 22.6 ml/100 g/min and intracellular brain pH was 6.86. Therefore, for the first 3 h, this ischemic penumbra was stable. At the fourth hour, both cerebral tissue perfusion and intracellular brain pH worsened. This suggests that the ischemic penumbra is a dynamic state. The rabbit is a good experimental model for the production of both severe and moderate focal ischemia.
Examination of Blood — Brain Barrier Permeability in Dementia of the Alzheimer Type with [68Ga]EDTA and Positron Emission Tomography
Authors: Schlageter Nicholas L. , Carson Richard E. , Rapoport Stanley I.
Published: April 2011

Positron emission tomography with [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA) was used to examine the integrity of the blood–brain barrier (BBB) in five patients with dementia of the Alzheimer type and in five healthy age-matched controls. Within a scanning time of 90 min, there was no evidence that measurable intravascular tracer entered the brain in either the dementia or the control group. An upper limit for the cerebrovascular permeability–surface area product of [68Ga]EDTA was estimated as 2 × 10−6 S−1 in both groups. The results provide no evidence for breakdown of the BBB in patients with dementia of the Alzheimer type.
Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [15O]Water and [11C]Butanol
Authors: Herscovitch Peter , Raichle Marcus E. , Kilbourn Michael R. , Welch Michael J.
Published: April 2011

We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H215O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H215O, may lead to an underestimation of CBF. We therefore validated the use of [11C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H215O, and thereby were able to calculate the extraction Ew and permeability–surface area product PSw of H215O. Measurements of the permeability of rhesus monkey brain to [11C]butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and [11C]butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H215O and [11C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [11C]butanol (53.1 ml/min-100 g) than with H215O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain–blood partition coefficient for [11C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.
Simultaneous 31P- and 1H-Nuclear Magnetic Resonance Studies of Hypoxia and Ischemia in the Cat Brain
Authors: Gyulai Laszlo , Schnall Mitchell , McLaughlin Alan C. , Leigh John S. , Chance Britton
Published: April 2011

The objective of this study was to evaluate simultaneous 31P/1H nuclear magnetic resonance (NMR) spectroscopy as a technique for monitoring and correlating changes in brain energy metabolism during hypoxia and ischemia. Five cats were studied with a protocol that involved 20 min of hypoxia (Pao2 20 mm), 60 min of recovery, 10 min of hypoxia with relative ischemia (bilateral carotid occlusion, PaO2 20 mm), and 60 min of recovery. Bifrontal and biparietal electrocorticograms (ECoG) were monitored continuously during the entire protocol. The results demonstrate that the degree of metabolic response is different in individual cats, but a number of quantitative relationships between metabolic parameters are consistently observed for all cats. First, there is agreement between increases in lactate and changes in intracellular pH; the observed relationship corresponds to an in vivo cerebral buffer capacity of 29 μmol/g/pH unit. Second, the delayed recovery of PCr is due to the effect of metabolic acidosis on the creatine kinase equilibrium and not to a delayed recovery of the ATP/ADP ratio. Third, the observed rate of lactate clearance from the cell is zero-order ( k = 0.36 μmol/g/min) for lactate levels >5 μm/g and may be composed of both lactate efflux from the cell and lactate oxidation.
Evidence for an Alanine, Serine, and Cysteine System of Transport in Isolated Brain Capillaries
Authors: Tayarani Ivan , Lefauconnier Jeanne-Marie , Roux Françoise , Bourre Jean-Marie
Published: April 2011

Brain capillaries isolated from 2-month-old male and female Sprague-Dawley rats were used to study the transport of neutral amino acids. The uptake of alanine, leucine, and alpha-methylaminoisobutyric acid (MeAIB) was a linear function of time for the first minute of incubation. Based on these observations, an incubation time of 1 min was used to measure transport activities. The intracellular water volume of the isolated capillaries was 2.2 μl/mg protein. This value was significantly lower (1.8 μl/mg protein) when measured in the absence of sodium. L-Alanine, L-serine, and L-cysteine were taken up from the abluminal surface of brain capillaries by a sodium- and energy-dependent, carrier-mediated system. This uptake, for the most part, was not inhibited by MeAIB. System ASC (alanine-serine-cysteine) appeared to be of primary importance for the transport of these amino acids in isolated brain capillaries. The apparent Km and Vmax values for L-alanine uptake by ASC transport, based on the Hofstee plot presentation, were 1.3 m M and 0.975 nmol/μl water content/min, respectively. The results also indicate that the transport of MeAIB and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH) was limited to the sodium-dependent system A (alanine) and the sodium-independent system L (leucine), respectively.
The Regional Cerebral Blood Flow in Patients under Chronic Hemodyalytic Treatment
Authors: Gottlieb D. , Mildworf B. , Rubinger D. , Melamed E.
Published: April 2011

Regional cerebral blood flow (rCBF) was measured by the xenon-133 inhalation method in an un-selected group of nine chronic hemodialysis patients before and after a single hemodialytic treatment. All patients underwent neurological, neuropsychological, and biochemical evaluations on the same occasions. Predialysis rCBF values did not differ from those obtained in age-matched normal controls. Following hemodialysis, there was a mild reduction in the rCBF by a mean of 7 ± 2.6% (p = 0.02). The posthemodialysis rCBF reduction was not associated with any neurological or cognitive dysfunction. The causes of hemodialysis-induced rCBF decreases are unknown, but increased blood viscosity and biochemical changes, such as urea reduction and blood alkalinization, may play a role.
GABA and Benzodiazepine Receptors in the Gerbil Brain after Transient Ischemia: Demonstration by Quantitative Receptor Autoradiography
Authors: Onodera Hiroshi , Sato Gen , Kogure Kyuya
Published: April 2011

Quantitative receptor autoradiography was used to measure the binding of γ-aminobutyric acid (GABA) and benzodiazepine receptors after ischemia by means of transient occlusion of bilateral common carotid arteries in the gerbil. [3H]Muscimol was used to label the GABAA receptors and [3H]funitrazepam to label central type benzodiazepine receptors. In the superolateral convexities of the frontal cortices, [3H]muscimol binding was increased in 60% of the animals killed 3 days after ischemia, and decreased in 67% of the animals killed 27 days after ischemia. Twenty-seven days after ischemia, [3H]funitrazepam binding in the substantia nigra pars reticulata increased to 252% of the control, though the increase in [3H]muscimol binding was not significant. In the dorsolateral region of the caudate putamen, marked neuronal necrosis and depletion of both [3H]muscimol and [3H]funitrazepam binding sites were observed 27 days after ischemia, the ventromedial region being left intact. In spite of the depletion of pyramidal cells in the CA1 region of the hippocampus, both [3H]muscimol and [3H]funitrazepam binding sites were preserved 27 days after ischemia. Since our previous study revealed that adenosine A1 binding sites were depleted in the CA1 subfield of the hippocampus after ischemia correlating with neuronal damage, GABAA and benzodiazepine receptors may not be distributed predominantly on the pyramidal cells in the CA1 region.
Dexamethasone Effects on [125I]Albumin Distribution in Experimental RG-2 Gliomas and Adjacent Brain
Authors: Nakagawa Hidemitsu , Groothuis Dennis R. , Owens Ernest S. , Fenstermacher Joseph D. , Patlak Clifford S. , Blasberg Ronald G.
Published: April 2011

A total of 72 RG-2 transplanted gliomas were studied in 58 rats at three time points (1, 30, 240 min) after intravenous injection of [125I]radioiodinated serum albumin ([125I]RISA). The animals were divided into two groups: a control group that received no treatment and a second group that was treated with five doses of 1.5 mg/kg of dexamethasone over 2.5 days. Local tissue concentrations of [125I]RISA were measured with quantitative autoradiography based on morphological features of the tumors and used to calculate the tissue distribution space. Two models were used to analyze the data. A two compartment model yielded estimates of local blood-to-tissue influx constants ( K1), lower limit extracellular volumes ( Ve), and plasma vascular volumes ( Vp) in different tumor regions. Treatment with dexamethasone consistently reduced the RISA distribution space in the RG-2 tumors; the reduction in Ve was statistically significant in almost all tumor regions: whole tumor Ve (mean ± SE) was reduced from 0.14 ± 0.02 ml g−1 in control animals to 0.08 ± 0.01 ml g−1 in dexamethasone treated animals. K1 and Vp were also decreased in all tumor regions after treatment with dexamethasone (whole tumor K1 decreased from 2.36 ± 0.89 to 0.83 ± 0.29 μl g−1 min−1 and Vp decreased slightly from 0.016 ± 0.013 to 0.010 ± 0.005 ml g−1 after dexamethasone treatment), but these changes were not statistically significant. A comparison of the tumor influx constants in control animals and the aqueous diffusion constants of two different size molecules (RISA and aminoisobutyric acid) suggests that the “pores” across RG-2 capillaries are large and may not restrict the free diffusion of RISA (estimated minimum pore diameter > 36 nm) and that the total pore area is ∼6.2 × 10−5 cm2 g−1 in RG-2 tumor tissue. The second model, which allows for diffusion and solvent drag of RISA across tumor capillaries and through the tissue, was used to analyze the distribution profiles of RISA in peripheral tumor and adjacent brain. This analysis was consistent with a small bulk flow of plasma-derived edema fluid (capillary filtration rate ≈ 0.8 μl g−1 min−1) and a larger component of free diffusion of RISA (K ≈ 2 μl g−1 min−1) through pores in the tumor vessels of control animals. Dexamethasone treatment markedly reduced or eliminated the filtration of plasma-derived fluid across tumor capillaries and the movement of RISA through the extracellular space by solvent drag. These effects may be mediated by a reduction in the size of the extracellular space and/or a decrease in the pore size of tumor capillaries and could represent an important mechanism for corticosteroid control of tumor and peritumoral brain edema.
The Reproducibility of the 133Xe Inhalation Technique in Resting Studies: Task Order and Sex Related Effects in Healthy Young Adults
Authors: Warach Steven , Gur Ruben C. , Gur Raquel E. , Skolnick Brett E. , Obrist Walter D. , Reivich Martin
Published: April 2011

Repeated applications of the 133Xe inhalation technique for measuring regional CBF (rCBF) were made during consecutive resting conditions in a sample of young healthy subjects. Subjects were grouped by order and by sex [nine had resting studies as the initial two measurements in a series of four measurement (six men, three women) and six had these measurements later (two men, four women)]. Three flow parameters were examined: f1 (fast flow) and IS (initial slope) for gray matter CBF, and CBF-15 for mean CBF (gray and white matter over 15-min integration), as well as w1, the percentage of tissue with fast clearing characteristics. With all groups combined, there were no significant differences between the two resting measurements, and high test-retest correlations were obtained for the flow parameters and w1. Analyses by order and sex grouping revealed, for the flow parameters, significant interactions of test-retest difference with order. Repeated initial studies showed reduced CBF from the first to second measurement, whereas resting studies performed later in the series showed no reduction. Interactions for test-retest difference with sex indicated that reduced CBF in serial measures was more pronounced for women. No hemispheric or regional specificity to account for these effects was found. Correction for PaCO2 differences did not alter these results. The results resemble data regarding habituation effects measured for other psychophysiologic measures, and suggest that reduction in CBF for consecutive measurements made on the same day may reflect habituation. This underscores the importance of controlling for effects of habituation on serial measurements of CBF and metabolism.
Protective Action of 1,3-Butanediol in Cerebral Ischemia. A Neurologic, Histologic, and Metabolic Study
Authors: Marie Christine , Bralet Anne-Marie , Bralet Jean
Published: April 2011

1,3-Butanediol (BD) is converted in the body to β-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia. The aim of this study was to determine if BD would reduce brain damage following cerebral ischemia. A transient forebrain ischemia of 30-min duration was induced by the four-vessel occlusion technique in control and BD-treated rats (25 mmol/kg, i.p.; 30 min prior to ischemia). BD treatment led to significant improvement of neurologic deficit during the 72-h recovery period and reduced neuronal damage in the striatum and cortex but not in the CA1 sector of the hippocampus. Evaluation of cerebral energy metabolism before and at the end of the ischemic period showed that the treatment did not change the preischemic glycolytic and energy metabolite levels but attenuated the ischemia-induced metabolic alterations. It increased energy charge, phosphocreatine, and glucose levels, and reduced lactate accumulation. The decrease in brain lactate concentration might account for the beneficial effects of BD by minimizing the neuropathological consequences of lactic acidosis.
Characteristics of Aminopeptidase Activity from Bovine Brain Microvessel Endothelium
Authors: Baranczyk-Kuzma Anna , Audus Kenneth L.
Published: April 2011

Blood–brain barrier (BBB) aminopeptidase activity was investigated using an in vitro model consisting of primary cultures of brain microvessel endothelium. Using two different substrates, both membrane-bound and soluble aminopeptidases were found to be associated with brain endothelium. That the enzyme activity was aminopeptidase activity was confirmed with the competitive inhibition of substrate degradation by typical aminopeptidase inhibitors puromycin and bestatin. The aminopeptidase activity was also competitively inhibited by enkephalin, met-enkephalin, and leu-enkephalin. Results from parallel experiments with cerebral gray matter and kidney confirm assay conditions. This report supports previous suggestions that aminopeptidases of the enzymatic BBB may play a role in regulating levels of circulating neuropeptides in the cerebrovasculature.
Cortical Hypometabolism and its Recovery following Nucleus Basalis Lesions in Baboons: A PET Study
Authors: Kiyosawa Motohiro , Pappata Sabina , Duverger Danielle , Riche Danielle , Cambon Henri , Mazoyer Bernard , Samson Yves , Crouzel Christian , Naquet Robert , MacKenzie Eric T. , Baron Jean-Claude
Published: April 2011

The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [18F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6–13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation. Moreover, unilateral NbM lesions also induced a transient reduction in contralateral cortical metabolic rate, the mechanisms of which are discussed. Explanation of these effects of cholinergic deafferentation in the primate could further our understanding of the metabolic deficits observed in dementia of the Alzheimer's type.
Metabolic Alterations Underlying the Development of Hypermetabolic Necrosis in the Substantia Nigra in Status Epilepticus
Authors: Ingvar Martin , Folbegrova Jaroslava , Siesjö Bo K.
Published: April 2011

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery. Labile energy metabolites were then analyzed in the SNPR and in the periaqueductal grey matter (PAG, control region). In the PAG, the metabolite changes during status epilepticus were similar to those reported for cerebral cortex and hippocampus. Measurements showed an unchanged ATP content and energy charge (97% and 98% of control, respectively) and an accumulation of lactate to 9.2 ± 0.6 μmol/g in the 60-min group. In the PAG, all metabolites measured had returned to control values after 60 min of recovery. In the SNPR, the perturbation of the energy metabolites was much more pronounced during status epilepticus. The concentration of ATP decreased to 75 ± 3%, the energy charge to 91% ± 12% and the adenylate pool to 86.7 ± 5.7% of control. Lactate accumulated to concentrations of 16.1 ± 1.8 μmol/g and 24.9 ± 2.3 μmol/g in the 20-min and 60-min groups, respectively. The concentration of lactate was still increased above control after 60 min recovery, whereas the concentration of ATP and the energy charge were lower than control. The findings demonstrate that sustained and intense neuronal activation can cause metabolic disturbance and thereby lead to necrosis. The very marked accumulation of lactic acid, likely due to mitochondrial failure, yields a very low intracellular pH, possibly explaining why a tissue necrosis, rather than selective neuronal necrosis, develops in the SNPR during status epilepticus.
Effect of Probenecid on Cerebral and Cisternal Cerebrospinal Fluid Lactate Content
Authors: MacMillan V.
Published: April 2011

In this study, the eisternal CSF contents of lactate and glucose were sequentially measured in free-moving rats that had been administered probenecid, 200 mg/kg−1, drug diluent, or no injections. In animals receiving either no injections or injections of drug diluent, CSF lactate and glucose were constant over a 6-h period (93–106% of control), whereas rats receiving probenecid showed increased lactate at 1 and 2 h (170 and 125% control, respectively) and increased glucose at 1, 2, and 3 h (169, 141 and 129% control, respectively). Cerebral cortex content of energy metabolites and lactate and blood lactate levels were statistically unaltered at 0.5–6 h exposure to probenecid, whereas cerebral and blood glucose contents were increased after 1 and 2 h exposure to probenecid. Rats exposed to 5% O2 and probenecid for 0.5 h showed a statistically higher CSF lactate at 0.5 and 1.5 h reoxygenation (169 and 168% control, respectively). A similar effect was also seen in rats exposed to 5% O2 and the 5-hydroxyindoleacetic acid (5-HIAA) transport inhibitor Na divalproate. The results suggested that the increase in CSF glucose was secondary to a probenecid-induced elevation of blood glucose, whereas the increase in CSF lactate seemed to be secondary to a reduced rate of efflux of lactate from the CSF. It is suggested that it may be possible to increase the CSF lactate content by mechanisms that are independent of direct effects on the processes of cerebral energy metabolism.
Cerebellar Diaschisis in Pontine Ischemia. A Case Report with Single-Photon Emission Computerized Tomography
Authors: Perani D. , Lucignani G. , Pantano P. , Gerundini P. , Lenzi G. L. , Fazio F.
Published: April 2011

Regional cerebral and cerebellar blood flows were studied by N, N, N'-trimethyl- N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3-propanediamine 2 HC1 (1-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.
Assessment of Goals and Obstacles in Data Acquisition and Analysis from Emission Tomography: Report of a Series of International Workshops
Authors: Mazziotta John C. , Koslow Stephen H.
Published: April 2011

All groups currently utilizing both single-photon emission computed tomography and positron emission tomography were surveyed in an effort to identify problems and potential solutions associated with data acquisition and analysis from these modalities. The results of these surveys indicated a need for an assessment of the problems and was followed by a series of international workshops, resulting in this report. Five specific areas of need were defined: physics, quality control, biomathematics, neuroanatomy, and computer science. Position papers identifying problems for the first three disciplines are included in this report, along with a recommendation for the organization of advisory boards to establish guidelines and to seek and disseminate information within these disciplines. Anatomical questions were substantially more difficult and will require a concerted experimental effort to further define the problems and validate potential solutions. Five subareas of the anatomical question are discussed in separate position papers. It was recommended that an anatomical data base obtained from magnetic resonance images be established and that this data base be used to validate the various functional image analysis schemes either currently in use or proposed for future application. Continuing and ongoing input will be necessary to sustain the efforts put forth in this document and to refine methods in parallel with our increasing knowledge and advancing technology. The capacity to objectively compare and exchange emission tomographic data collected by the resultant methods should justify the efforts and interest in these important issues.
Early Effects of Tetraethylammonium Chloride on the Contractile Properties of Isolated Rabbit Basilar Arteries
Authors: Young A. R. , Säveland H. , Pickard J. D. , Perry S. , Brandt L. , Ljunggren B.
Published: April 2011

The acute vascular effects of tetraethylammonium chloride (TEA) were examined on annular segments of rabbit basilar arteries, Contractions induced by the potassium channel blocker were compared with those obtained for potassium chloride, 5-hydroxytryptamine (5-HT) and norepinephrine (NE), The greater magnitude of the contractions was of the following order: [K+] > 5-HT> TEA> NK High concentrations of TEA alone (10−2 M) generated spontaneous oscillatory contractions in cerebral vessels that were normally quiescent, Low concentrations of TEA (10−8-10−6 M), which had no vasomotor properties per se, enhanced the contractile response of submaximal concentrations of 5-HT (10−7 M) and NE (3 × 10−6 M) and attenuated the contraction produced by 60 m M [K+], An increased vascular response to the amines was still evident up to 3 h after the addition of TEA despite frequent rinsing with fresh buffer solutions. On arteries precontracted with TEA (10−2 M), but not high [K +], the subsequent addition of 5-HT (10−7 M) still induced a powerful constriction. Repeated concentration-response curves for [K+] were reproducible and, in the presence of TEA (10−8 or 10−6 M), the curve was displaced to the right in a competitive manner. A higher concentration of TEA (10−4 M) was devoid of any blocking properties on the [K+]-induced response whereas, at 10−3 M TEA, the response was potentiated, as evidenced by a shift of the curve to the left. Interactions between TEA and the cumulative response to 5-HT were difficult to interpret. Repeated exposures of the artery to 5-HT resulted in an increased maximal response with each determination (EAm = 127 ± 9% and 149 ±: 14% of control values following the second and third applications, respectively). With TEA (10−6 M), the increase in the maximal contractile effect noted previously was not observed. Contractions induced by single concentrations of TEA (10−2 M) or [K+] (60 m M) were calcium dependent, were abolished completely in a calcium-free medium, and were depressed by the calcium antagonist nimodipine. 5-Hydroxytryptamine-induced contractions (10−5 M) were less sensitive to withdrawal of calcium from the extracellular medium (31 ± 6% relative to the maximal response at 4 m M calcium). Hence, an acute reduction in potassium conductance in cerebrovascular smooth muscle produced by TEA has complex, concentration-dependent effects and reproduces only part of the spectrum of effects of cisternal injection of blood on cerebrovascular reactivity.
Activation Autoradiography: Imaging and Quantitative Determination of Endogenous and Exogenous Oxygen in the Rat Brain
Authors: Kawashima Koichiro , Iwata Ren , Kogure Kyuya , Ohtomo Hitoshi , Orihara Hikonojo , Ido Tatsuo
Published: April 2011

Endogenous and exogenous oxygen in the rat brain were quantitatively determined using an autoradiographic technique. The oxygen images of frozen and dried rat brain sections were obtained as 18F images by using the 16O (3He,p)18F reaction for endogenous 16O images and the 18O(p,n)18F reaction for endogenous and exogenous 18O images. These autoradiograms demonstrated the different distribution of oxygen between gray and white matter. These images also allowed differentiation of the individual structures of hippocampal formation, owing to the differing water content of the various structures. Local oxygen contents were quantitatively determined from autoradiograms of brain sections and standard sections with known oxygen contents. The estimated values were 75.6 ± 4.6 wt% in gray matter and 72.2 ± 4.0 wt% in white matter. The systematic error in the present method was estimated to be 4.9%.
Cortical Vasodilatation Produced by Vasoactive Intestinal Polypeptide (VIP) and by Physiological Stimuli in the Cat
Authors: Yaksh Tony L. , Wang Jia-Yi , Go V. L. W. , Harty Gail J.
Published: April 2011

In chloralose-urethanized cats, vasoactive intestinal peptide (VIP), applied by superfusion in steady-state concentration (10−10–10−6 M) onto cortical vessels in situ resulted in a rapid concentration-dependent vasodilatation in vessels that were mildly constricted by prostaglandin F2α (PGF2α) (5 × 10−5 M) or hypocarbia (PaCO2 = 26). The maximum dilatation produced by VIP (10−6 M) was about 60% over baseline in pial arteries and 40% in pial veins. Blockade of local neuronal activity with tetrodotoxin (TTX) (10−5 M) had no effect on the VIP-evoked dilation of pial vessels. Activation of the cortex by either direct electrical stimulation or indirectly by stimulation of the mesencephalic reticular formation (MRF) resulted in a rapid dilatation of pial arterioles and venules. The vasodilatory effects of VIP and of cortical activation via direct cortical stimulation were not blocked by phentolamine (10−4 M), propranolol (10−4 M), atropine (10−4 M), or naloxone (10−4 M), indicating that the stimulated vasodilatation was not mediated by adrenergic, cholinergic, or opiate receptors. The dilatory effects of MRF, but not direct cortical stimulation, were not blocked by TTX. VIP antiserum (1:25) preincubated in cortical cups had no effect on resting vessel diameter, but resulted in a significant, though subtotal, reduction in the vasodilatation elicited by direct cortical and MRF stimulation. Normal rabbit sera or VIP antiserum preincubated with saturating amounts of VIP were ineffective. In similar experiments, pial arteriolar and venular dilation evoked by hypercarbia was not attenuated by cortically applied VIP antisera. These observations suggest that pial dilation evoked by local increases in neuronal activity may be mediated in part by the local release of VIP from intrinsic neurons. Such a substrate would define a close obligatory coupling between local neuronal activation and local perfusion, such that nutritive flow could be enhanced prior to the onset of any metabolic deficit.
Estimation of Cerebral Oxygen Utilization Rate by Single-Bolus 15O2 Inhalation and Dynamic Positron Emission Tomography
Authors: Meyer E. , Tyler J. L. , Thompson C. J. , Redies C. , Diksic M. , Hakim A. M.
Published: April 2011

This study shows that regional CMRO2 can be estimated by means of nonlinear regression using dynamic positron emission tomographic data acquired during 1 min following single-bolus inhalation of 15O2. The feasibility of simultaneous estimation of CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), and CMRO2 was assessed by simulations using the model of Mintun et al. Four oxygen metabolic measurements, each consisting of a CBF, CBV, and 15O2 bolus study, were carried out on three volunteers. Regional values for CBF, CBV, OER, and CMRO2 were derived in two ways: from the fits of the time-activity curves of the dynamic 15O2 bolus study alone [CMRO2(fit)] and from the three separate studies [CMRO2 (control)]. For the 56 regions of interest analyzed, using a fit interval of 60 s, CMRO2(fit) was 93.4 ± 7.8% of CMRO2(control) (mean ± SD) with a correlation coefficient of r = 0.95. CMRO2(control) ranged from 87 to 290 μmol/min/100 g. Individual simultaneous estimates of CBF, CBV, and OER were not reliable. Finally, we found that the validity of the model was limited in practice to the first minute after tracer inhalation.
Cerebral Hemispheric and Contralateral Cerebellar Hypoperfusion during a Transient Ischemic Attack
Authors: Perani Daniela , Gerundini Paolo , Lenzi Gian Luigi
Published: April 2011

We studied a 79-year-old woman within 3 h of the onset of a motor aphasia and a right hemiparesis. Single photon emission computed tomography (SPECT) showed a 24% decrease in the perfusion of the left middle cerebral artery territory and a 16% reduction in the perfusion of the right cerebellum. A mild naming difficulty was the neurological deficit at the end of the SPECT examination, and complete recovery was achieved within 24 h. Repeated SPECT study 10 days later was normal. This is the first report of focal hemispheric and contralateral cerebellar hypoperfusion in transient cerebral ischemia.
Sensitivity of Cerebral Glucose Metabolism to Age, Gender, Brain Volume, Brain Atrophy, and Cerebrovascular Risk Factors
Authors: Yoshii Fumihito , Barker William W. , Chang Jen Yueh , Loewenstein David , Apicella Anthony , Smith David , Boothe Thomas , Ginsberg Myron D. , Pascal Shlomo , Duara Ranjan
Published: April 2011

In 76 normal volunteers studied by positron emission tomography, with [18F]fluorodeoxyglucose, CMRglu was significantly lower in the elderly as compared with young subjects and significantly higher in females relative to males. However, in 58 of these subjects who also had magnetic resonance imaging scans, age and gender were found to be unrelated to CMRglu, when the effects of brain volume and brain atrophy on CMRglu were partialed out using covariate analyses. Individually, brain volume was found to have a significant effect on CMRglu, explaining ∼17% of the variability in CMRglu measures and brain atrophy explaining ∼8% of the variance in CMRglu. Together these two measures accounted for ∼21% of the variance. Cerebrovascular risk factors in normal subjects were not found to affect mean CMRglu or the variability of CMRglu measures. In this study almost 80% of the variance in CMRglu could not be explained by any of the factors that had been considered. This implies a lack of sensitivity of absolute values of global CMRglu to the mild effects of brain dysfunction. Although some of the unexplained variance is probably methodological in origin, physiological factors that are difficult to quantify, such as the state of arousal, are likely to be contributory as well.
Rapid Monitoring of Intraoperative Cerebral Blood Flow Using 133Xe
Authors: Young William L. , Prohovnik Isak , Ornstein Eugene , Lucas Louis R. , Wang Theodore S. T. , Correll James W. , Alderson Philip O.
Published: April 2011

This study examined the feasibility of rapid rCBF monitoring using 133Xe as a tracer during operative procedures. We compared the initial slope index derived from two bicompartmental and one monocompartmental physiological models. The single-compartment model requires only 3 min of monitoring, whereas the bicompartmental models, thought to be more reliable, require 11 min of clearance. Data were collected from 26 patients undergoing carotid endarterectomy. Approximately 20 mCi of 133Xe in saline was injected i.v. for up to five measurements per patient, for a total of 117 measurements. The robustness of the regression for the three parameters ( r = 0.781–0.99, p < 0.0001) suggests that the three parameters are closely related. This is supported by similarity of the slopes of the regression lines (between 0.944 and 1.25) and the mean ± SD of the three rCBF models (24.9–27.5 ± 12.0–14.3 ml 100 g−1 min−1). Similar results were obtained for individual detectors, despite the expected higher variability. For intraoperative use in surgical procedures in which physiological conditions may change rapidly and i. v. injections of tracer must be used, a rCBF index that quickly and accurately reflects flow conditions is useful. Our data suggest that the single-compartmental Wyper index may be used to provide information about cerebral perfusion that is as accurate and robust as bicompartmental models, but requires only one-quarter of the data collection time.
Origins and Pathways of Cerebrovascular Vasoactive Intestinal Polypeptide-Positive Nerves in Rat
Authors: Suzuki Norihiro , Hardebo Jan Erik , Owman Christer
Published: April 2011

In order to clarify the origins and pathways of vasoactive intestinal polypeptide (VlP)-containing nerve fibers in cerebral blood vessels of rat, denervation experiments and retrograde axonal tracing methods (true blue) were used. Numerous VIP-positive nerve cells were recognized in the sphenopalatine ganglion and in a mini-ganglion (internal carotid mini-ganglion) located on the internal carotid artery in the carotid canal, where the parasympathetic greater superficial petrosal nerve is joined by the sympathetic fibers from the internal carotid nerve, to form the Vidian nerve. VIP fiber bridges in the greater deep petrosal nerve and the internal carotid nerve reached the wall of the internal carotid artery. Two weeks after bilateral removal of the sphenopalatine ganglion or sectioning of the structures in the ethmoidal foramen, VIP fibers in the anterior part of the circle of Willis completely disappeared. Very few remained in the middle cerebral artery, the posterior cerebral artery, and rostral two-thirds of the basilar artery, whereas they remained in the caudal one-third of the basilar artery, the vertebral artery, and intracranial and carotid canal segments of the internal carotid artery. One week after application of true blue to the middle cerebral artery, dye accumulated in the ganglion cells in the sphenopalatine, otic and internal carotid mini-ganglion; some of the cells were positive for VIP. The results show that the VIP nerves in rat cerebral blood vessels originate: (a) in the sphenopalatine, and otic ganglion to innervate the circle of Willis and its branches from anterior and caudally and (b) from the internal carotid mini-ganglion to innervate the internal carotid artery at the level of the carotid canal and to some extent its intracranial extensions.
Cerebral Glucose Utilization in Rats is Not Altered by Hindlimb Restraint or by Femoral Artery and Vein Cannulation
Authors: Soncrant Timothy T. , Holloway Harold W. , Stipetic Mark , Rapoport Stanley I.
Published: April 2011

The effects of immobilization and femoral artery and vein cannulation on resting rates of local cerebral glucose utilization (LCGU) were measured in 35 brain regions of awake rats by using the quantitative, autoradiographic [14C]2-deoxy-D-glucose ([14C]DG) technique. Three groups of rats were cannulated on the previous day, and LCGU was measured under conditions of no restraint, 4 h of hindlimb restraint, or acute, four-limb immobilization. A fourth group represented the conventional preparation for [14C]DG experiments, with same-day cannulation followed immediately by 4 h of hindlimb restraint. Plasma catecholamines, corticosterone, and glucose concentrations were measured in all groups; all were elevated significantly above values in unrestrained animals only during four-limb immobilization. LCGU was unchanged by same-day surgery, hindlimb restraint, or both. During four-limb immobilization, LCGU was reduced by 25% in the dorsal hippocampus, and to a lesser extent in the anteroventral thalamic nucleus. It was increased only in the lateral habenula (42%). We conclude that two stressors of the experimental preparation (same-day surgery and hindlimb restraint) do not influence LCGU measurements by the [14C]DG method. More severe, acute stress selectively alters LCGU in a few rat brain regions.
L-Type Calcium Channels are Modified in Rat Hippocampus by Short-Term Experimental Ischemia
Authors: Magnoni M. S. , Govoni S. , Battaini F. , Trabucchi M.
Published: April 2011

Increasing evidence suggests a role for calcium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modified by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number of 3H-PN 200-110 binding sites in the hippocampus ipsilateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum. The changes in hippocampus are transient: 96 h after the occlusion, binding parameters return to the control range. The modifications of the binding characteristics in the hippocampus may be related to alterations of Ca2+ fluxes through L-type calcium channels.