bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Uniqueness of Cerebral Blood Flow Measured by the in vivo Autoradiographic Strategy and Positron Emission Tomography
Authors: Howard Bernard E. , Ginsberg Myron D. , Hassel William R. , Lockwood Alan H. , Freed Philip
Published: April 2011

Factors are examined in this report which govern the uniqueness and sensitivity of regional cerebral blood flow (rCBF), as determined by an in vivo autoradiographic strategy and positron emission tomography (PET), and a series of theorems is derived which specify conditions under which a unique relationship between cumulative cranial activity of the tracer ( C) and regional blood flow ( f) may be assured. It is demonstrated that, independent of the specific form of the arterial tracer input function, flow is a unique function of C whenever the start time ( T1) of the PET scan is coincident with the start of tracer infusion. Other theorems state that, even for nonzero T1s, a unique solution for flow may be expected, as long as the duration of the scan is sufficiently short. The implementation of this theory is illustrated using arterial tracer activity curves obtained in three normal subjects by a multiple arterial sampling procedure following the bolus i. v. infusion of 20–30 μCi of [15O]water. Based on these arterial curves, it is confirmed that the C vs. f relationship resulting from scan parameters T1 = 0 and T2 = 1.5 min (i.e., a PET scan of 90 s commencing with tracer infusion) has an excellent separation of flow values within the range of physiological interest, whereas a 90-s scan beginning at time T1 = 1.7 min results in poorer separation of flow values and loss of the monotonic relationship between C and f at higher flows. The results of this study serve to clarify the in vivo autoradiographic method for measuring rCBF in humans and help to define favorable study parameters for assuring uniqueness and sensitivity of the flow measurement.
Effects of Indomethacin and Ibuprofen on Cerebral Metabolism and Blood Flow in Traumatized Brain
Authors: Pappius Hanna M. , Wolfe Leonhard S.
Published: April 2011

Local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) were studied by autoradiographic techniques in indomethacin- and ibuprofen-treated rats with focal cortical freezing lesions. Widespread depression of LCGU, which developed with time after the lesion in untreated animals was significantly diminished by the prostaglandin synthetase inhibitors indomethacin (single injection 7.5 mg/kg) and ibuprofen (36 mg/kg/day). Both drugs were effective when given 6 h before or up to 24 h after the lesion was made. The effect of the drugs was most striking in cortical areas of the traumatized hemisphere, where the depression was most profound in untreated animals. Thus, 3 days afer the lesion, average LCGU in these regions was 46%, 86%, and 98% of normal in untreated, indomethacin-pretreated, and ibuprofen-pretreated rats, respectively. Prostaglandin formation was completely inhibited in the lesion area in the indomethacin-treated rats (PGF2α 1.8 ng/g, compared to 57.5 ng/g in untreated and 1.4 ng/g in nonlesioned animals). The results suggest that some components of the prostaglandin system are involved in mechanisms underlying a widespread depression in functional state of the rat brain that develops in response to injury. In control animals, indomethacin was shown to have a biphasic effect on LCBF, an early depression shown previously by others followed at 24 h by a considerable increase.
An Inhibitor of Cerebral Uptake of Noradrenaline in Jaundiced Blood Plasma
Authors: Bradbury M. W. B. , Bloom D. S. , McDowell M.
Published: April 2011

The permeability of the blood–brain barrier to noradrenaline was estimated in rats with bile duct ligation by intracarotid injection of [14C]-l-noradrenaline, 3H2O, and [113mIn]ethylene diamine tetraacetate (EDTA) under pentobarbitone anaesthesia. Brain uptake of [14C]noradrenaline was expressed as a percentage of that of 3H2O (brain uptake index, BUI) and corrected for the “blood background” by the 113mIn. The BUI of noradrenaline (1.20 ± 0.19) was not increased in jaundice (0.78 ± 0.18). The capacity of oxygenated homogenates of rat brain to remove noradrenaline was measured. The presence of jaundiced plasma always caused a substantial suppression of noradrenaline removal. No effect of jaundice on specific radioactive assays for catechol-O-methyl transferase (COMT) or monoamine oxidase (MAO) could be demonstrated.
Innervation of Capillaries by Local Neurons in the Cat Hypothalamus: A Light Microscopic Study with Horseradish Peroxidase
Authors: Rennels Marshall L. , Gregory Thomas F. , Fujimoto Katsukuni
Published: April 2011

The protein tracer horseradish peroxidase (HRP) has been used in an attempt to define the cell bodies of origin of “nonadrenergic” varicose axons which terminate on the walls of hypothalamic capillaries. Capillaries in this region are also known to receive direct axonal contacts from adrenergic neurons in the pontine locus ceruleus. Solutions of HRP were infused into the lateral ventricles of adult cats of either sex and permitted to circulate in the cerebrospinal fluid spaces for 10 min, 20 min, or 2 h. During these periods HRP entered the perivascular spaces around penetrating arterioles and spread into the surrounding extracellular spaces of the hypothalamus. Certain neurons in the periarteriolar neuropil were consistently labeled by the tracer after all three circulation periods. These cells, including all of their processes, could be visualized in detail. Most neurons, by contrast, did not accumulate HRP. The axons of some tracer-filled neurons terminated on the walls of capillaries in the immediate vicinity of the penetrating arteriole. The arrangement and distribution of these cells suggest that they may provide a substrate for local neural influences on the hypothalamic microcirculation.
Cerebral Metabolic Relationships for Selected Brain Regions in Healthy Adults
Authors: Metter E. Jeffrey , Riege Walter H. , Kuhl David E. , Phelps Michael E.
Published: April 2011

The local cerebral metabolic rate for glucose was determined in 26 regions of the brain in 31 healthy subjects who underwent resting fluorodeoxyglucose positron emission tomography. Intercorrelations among the 26 regional measures were accepted as reliable at p < 0.01 (r > 0.45), uncorrected for the number of measures. From the matrix two apparently separate functional metabolic systems were identified: (1) a superior system involving the superior and middle frontal gyri, the inferior parietal lobule, and the occipital cortex; and (2) an inferior system involving the inferior frontal, Broca's, and posterior temporal regions. Evidence is presented to suggest that the superior system is involved in visual processing, memory recognition, and decision making, while the inferior system seems to at least participate in language-related functions.
Delayed Neuronal Recovery and Neuronal Death in Rat Hippocampus following Severe Cerebral Ischemia: Possible Relationship to Abnormalities in Neuronal Processes
Authors: Petito C. K. , Pulsinelli W. A.
Published: April 2011

Mechanisms involved in the postischemic delay in neuronal recovery or death in rat hippocampus were evaluated by light and electron microscopy at 3, 15, 30, and 120 min and 24, 36, 48, and 72 h following severe cerebral ischemia that was produced by permanent occlusion of the vertebral arteries and 30-min occlusion of the common carotid arteries. During the early postischemic period, neurons in the Ca1 and Ca3 regions both showed transient mitochondrial swelling followed by the disaggregation of polyribosomes, decrease in rough endoplasmic reticulum (RER), loss of Golgi apparatus (GA) cisterns, and decrease in GA vesicles. Recovery of these organelles in Ca3 neurons was first noted between 24 and 36 h and was accompanied by a marked proliferation of smooth endoplasmic reticulum (SER). Many Ca1 neurons initially recovered between 24 and 36 h, but subsequent cell death at 48–72 h was often preceded by peripheral chromatolysis, constriction and shrinkage of the proximal dendrites, and cytoplasmic dilatation that was continuous with focal expansion of RER cisterns. Because SER accumulates in resistant Ca3 neurons and proximal neuronal processes are damaged in vulnerable Ca1 neurons, we hypothesize that delayed cell recovery or death in vulnerable and resistant postischemic hippocampal neurons is related to abnormalities in neuronal processes.
Three-Dimensional Architecture of Cerebral Microvessels with a Scanning Electron Microscope: A Cerebrovascular Casting Method for Fetal and Adult Rats
Authors: Yoshida Yasuji , Ikuta Fusahiro
Published: April 2011

Vascular casting for scanning electron microscopic studies on microvascular architecture is in common use for various visceral organs in the field of anatomy. However, only a few studies have been performed on the brain using the previously reported casting method, and no detailed descriptions deal with suitable methodology for producing brain vascular casts. Our casting method, introduced here, for the CNS from the fetal to the adult stage involves the following modifications: (1) Perfusion fixation of the brain is carried out before injecting the plastic resin for casting into the cerebral blood vessels; (2) digestion of nervous tissue is accomplished with a sodium hydroxide and sodium hypochlorite solution; and (3) vascular casts are dried by a freeze-drying method, while the nondigested brain slices opposite the casts can be investigated with light microscopy and transmission electron microscopy. This modified casting method enables one to represent the microvascular system of the rat brain three-dimensionally from embryonal day 17 onward. It is hoped that this method will prove to be a useful tool in morphological vascular research on the nervous system.
Inhibition by Verapamil of Ischemic Ca2+ Uptake in the Rabbit Hippocampus
Authors: Hagberg Henrik , Lehmann Anders , Hamberger Anders
Published: April 2011

In the study described here a perfusion-dialysis system was used for recording ionic changes in the hippocampus during ischemia. Local perfusion with a Ca2+ entry blocker (verapamil) inhibited the fall in extracellular Ca2+ concentration which occurs in ischemia. The data consequently suggest that intracellular Ca2+ accumulation during ischemia can be blocked. A Ca2+ antagonist such as verapamil may thus improve postischemic neuronal recovery via a direct effect on parenchymal cells in addition to the previously suggested vascular effects.
Dependency of Blood Flow Velocity in the Middle Cerebral Artery on End-Tidal Carbon Dioxide Partial Pressure—A Transcranial Ultrasound Doppler Study
Authors: Markwalder Thomas-Marc , Grolimund Peter , Seiler Rolf W. , Roth Fritz , Aaslid Rune
Published: April 2011

The end-tidal carbon dioxide partial pressure (PCO2) response curves for the flow velocity in the middle cerebral artery were studied in 31 normal subjects with transcranial Doppler techniques. An exponential curve with an exponent of 0.034 mm Hg−1 was found to be a good fit to the recorded data. By means of this relationship, recordings of flow velocity in cerebral arteries can be normalized to a standard value of PCO2. Physiological aspects of cerebrovascular reactivity to PCO2 and the clinical implications of the PCO2 response curve are discussed. The normal material provides a reference for assessing pathological responses.
Decreased Cortical Glucose Utilization after Ibotenate Lesion of the Rat Ventromedial Globus Pallidus
Authors: London Edythe D. , McKinney Michael , Dam Mauro , Ellis Albert , Coyle Joseph T.
Published: April 2011

Rats received unilateral injections of ibotenic acid (12 μg) or vehicle in the ventromedial globus pallidus to lesion the primary source of cortical cholinergic innervation. At 3 or 28–32 days postinjection, the regional cerebral metabolic rate for glucose (rCMRglu) was measured by the 2-deoxy-d-[14C]glucose technique in nine cortical areas, the anterior thalamus, and the dorsal hippocampus. Effects of oxotremorine (0.1 mg/kg i.p.) on rCMRglu in these areas were assessed in ibotenic acid–lesioned and sham-treated rats. Significant effects of ibotenic acid injections and hemispheric asymmetries in rCMRglu were observed in all cortical areas (p ≤ 0.05), but not in the anterior thalamus or hippocampus. Cortical rCMRglu generally was lower in the lesioned hemisphere 3 days after ibotenic acid injections, but not after sham treatments. Hemispheric asymmetries were not apparent 28–32 days after pallidal lesions. Oxotremorine produced significant effects in the frontoparietal cortex and anterior thalamic nuclei. In the frontoparietal cortex, rCMRglu was 32% lower in the ibotenate-lesioned hemisphere as compared with the contralateral hemisphere. Oxotremorine did not eliminate hemispheric asymmetry, but increased rCMRglu in the lesioned frontoparietal cortex by 38%. Results support the views that cortical metabolic decrements in Alzheimer's disease are due in part to loss of subcortical cholinergic innervation and that muscarinic agonists may partially reverse these decrements.
A Light and Electron Microscopic Immunohistochemical Study of Vasoactive Intestinal Polypeptide— And Substance P-Containing Nerve Fibers along the Cerebral Blood Vessels: Comparison with Aminergic and Cholinergic Nerve Fibers
Authors: Itakura Toru , Okuno Takashi , Nakakita Kazuo , Kamei Ichiro , Naka Yutaka , Nakai Kunio , Imai Harumichi , Komai Norihiko , Kimura Hiroshi , Maeda Toshihiro
Published: April 2011

Vasoactive intestinal polypeptide (VIP)– and substance P–containing nerve fibers were observed in the cerebral blood vessels using an immunohistochemical technique. VIP-containing nerve fibers distributed in a spiral pattern, similar to that of muscle cells. Under electron microscopic observation, VIP-immunoreactive terminals lay close to a muscle cell in the inner layer of the adventitia. In contrast, substance P–containing nerve fibers showed a meshwork pattern in the outer layer of the adventitia. Using both acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers revealed almost the same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role in the smooth muscle control of the blood vessels, whereas substance P–containing nerve fibers may not take part in muscle control.
Monoamine Oxidase Activity in the Cerebral Vasculature: Comparison between Fresh Microvessels from Different Structures and Cell Cultures Derived from Microvessels
Authors: Sercombe R. , Lasbennes F. , Drouet L. , Dosne A. M. , Seylaz J.
Published: April 2011

Monoamine oxidase (MAO) activity was studied in various preparations of porcine brain microvessels to explore further the role of this enzyme in the blood–brain barrier to catecholamines. No difference was noted ( Vm and Km) between microvessels isolated from three structures (caudate nucleus, thalamus, and cerebral cortex) in which the responses to circulating catecholamines in vivo are markedly different. Large and small microvessels from the caudate nucleus and the thalamus presented the same specific activity. Cell cultures obtained from small microvessels were rich in endothelial cells as identified by the presence of Factor VIII–related antigen. These preparations displayed an MAO activity about ninefold less than freshly isolated microvessels, although their prostaglandin synthetase activity appeared normal. These results suggest that MAO activity is not the main factor determining the regional differences in the cerebrovascular reactions to catecholamines, that MAO is not specifically localized in the endothelium but must be also present in the smooth muscle, and that the MAO activity is greatly decreased during cell culture.
Influence of in vitro Lactic Acidosis and Hypercapnia on Respiratory Activity of Isolated Rat Brain Mitochondria
Authors: Hillered Lars , Ernster Lars , Siesjö Bo K.
Published: April 2011

Respiratory activity and the ADP/O ratio of isolated rat brain mitochondria were measured following incubation with varying concentrations of lactic acid in reaction media buffered either with bicarbonate and CO2 or with phosphate alone, at a pH of 7.1. Increasing lactic acid levels caused a progressive decrease in substrate-, phosphate-, and ADP-stimulated (State 3) respiration and ADP/O ratios. Fifteen millimolar lactic acid, pH 6.4, caused ∼50% inhibition of State 3 respiration (with malate + glutamate as substrate). At lower pH values (5.3–6.1), addition of ADP caused little or no increase in O2 consumption; i.e., ATP formation ceased. Addition of lactic acid at constant pH moderately affected respiratory control ratios but did not change State 3 respiration or ADP/O ratios. Thus, the effect of lactic acid was related to the pH change. Increasing CO2 concentrations in the reaction medium had similar effects on mitochondrial respiration, indicating that changes in extramitochondrial pH rather than in transmembrane H+ gradients determined the respiratory alterations. Following a 5-min incubation of mitochondria with lactic acid, pH 6.1, there was an incomplete recovery of State 3 respiration and respiratory control ratios. It is concluded that mitochondrial respiration is inhibited by a decrease in pH which, if excessive, may lead to a permanent suppression of ATP production. These results may, at least partly, explain the deleterious effects of enhanced lactic acidosis in brain ischemia.
Erythrocyte Extracts Enhance Neurogenic Vasoconstriction of Dog Cerebral Arteries in vitro
Authors: Lee Tony J.-F. , McIlhany Michael P. , Sarwinski Susan
Published: April 2011

Cerebral blood vessels of the dog have been shown to receive vasodilator and constrictor nerves. In isolated ring arterial preparations, neurogenic vasodilation was blocked while neurogenic vasoconstriction was potentiated by hemolysates isolated from hemolyzed erythrocytes. These results suggest that an overall increase in cerebral neurogenic vasoconstriction may occur in vivo following subarachnoid hemorrhage. The significance of this finding in the pathogenesis of cerebral vasospasm is discussed.
An Evaluation of Errors in the Determination of Blood Flow by the Indicator Fractionation and Tissue Equilibration (Kety) Methods
Authors: Patlak Clifford S. , Blasberg Ronald G. , Fenstermacher Joseph D.
Published: April 2011

In this report, the effects of various errors and plasma time courses of indicator concentration on the accurate determination of cerebral blood flow ( F) are theoretically analyzed for the tissue equilibration and the indicator fractionation techniques. For the indicator fractionation technique, the impact of sample timing and tissue assaying errors and of indicator backflux were examined; for the tissue equilibration method, errors in the value of the partition coefficient (Λ), sample timing, and tissue assaying were considered. The recommended ways to decrease the effects of errors in the indicator fractionation technique are to administer the indicator by an intravenous bolus and to sample the tissue about 10 s thereafter. Possible errors in the assessment of F by the tissue equilibration technique are diminished by using an indicator infusion schedule which yields a continuous rise in arterial concentration and by selecting a 30-s experiment duration. Surprisingly, the impact of sample timing errors is greater on the determination of F with the tissue equilibration method than with the indicator fractionation technique. For the chosen plasma time courses, there is always a backflux error in an indicator fractionation estimation of F, and this error increases as the flow rate increases. Thus, provided the sample timing and tissue assay errors are small and the value of Λ is known, the tissue equilibration method is the more accurate of the two. If Λ is unknown, then the indicator fractionation technique should be used. In many cases, the indicator fractionation method will provide as accurate an estimate of F as will the tissue equilibration method.
A Method to Quantitate the Fractional Extraction of Rubidium-82 across the Blood—Brain Barrier Using Positron Emission Tomography
Authors: Lammertsma Adriaan A. , Brooks David J. , Frackowiak Richard S. J. , Heather Jon D. , Jones Terry
Published: April 2011

Previously, rubidium-82 and positron emission tomography (PET) have been used to assess qualitatively the integrity of the blood-brain barrier (BBB). In this report, a method is described to measure the fractional extraction of rubidium across the BBB using the constant intravenous infusion of rubidium-82. In addition, the continuous inhalation of oxygen-15-labelled carbon dioxide is needed to measure regional CBF, and it is also necessary to measure regional cerebral blood volume. The assumptions underlying the model are identified, and the impact of deviations from these assumptions is described. From radiation dose and statistical considerations, it is shown that for normal cerebral tissue and the PET scanner used in this study, the rubidium extraction fraction can be quantitated only for regions as large as a cerebral hemisphere. However, quantitation is also possible for smaller regions where the focal extraction of rubidium is increased.
Effect of Prolonged and Intermittent Hypoxia on Some Cerebral Enzymatic Activities Related to Energy Transduction
Authors: Dagani F. , Marzatico F. , Curti D. , Zanada F. , Benzi G.
Published: April 2011

The adaptation to repeated, alternate normobaric hypoxic and normoxic exposures (12 h/day, for 5 days) and to pharmacological treatment was evaluated by studying the specific activities of some enzymes related to cerebral energy metabolism. Measurements were carried out on (a) the homogenate in toto, (b) the purified mitochondrial fraction, and (c) the crude synaptosomal fraction in different areas of rat brain—cerebral cortex, hippocampus, corpus striatum, hypothalamus, cerebellum, and medulla oblongata. The adaptation to intermittent normobaric hypoxic-normoxic exposures was characterized by significant modifications of some enzyme activities in synaptosomes (decrease of cytochrome oxidase activity in the hippocampus, corpus striatum, and cerebellum; decrease of malate dehydrogenase activity in the cerebellum) and in the purified mitochondrial fraction (increase of succinate dehydrogenase activity in the corpus striatum). Daily treatment with three doses of naftidrofuryl (10, 15, and 22.5 mg/kg i.m.) modified some enzyme activities affected or unaffected by intermittent hypoxia and, particularly, decreased acetylcholinesterase activity.
Age-Related Reductions in Cerebral Vasomotor Reactivity and the Law of Initial Value: A 4-Year Prospective Longitudinal Study
Authors: Rogers Robert L. , Meyer John S. , Mortel Karl F. , Mahurin Roderick K. , Thornby John
Published: April 2011

A group of 51 neurologically normal, middle-aged and elderly volunteers (aged 35–86 years; mean age 63.24 years) with and without risk factors for stroke were given annual tests of cerebral vasomotor reactivity to assess any changes in the cerebral vascular capacitance associated with advancing age that might alter cerebral vasomotor reactivity. Cerebral vasomotor reactivity was estimated as the difference in bihemisphere gray matter CBF measured by the 133Xe inhalation method in the steady state breathing room air, followed by a second measurement during inhalation of 100% oxygen. There were significant and progressive reductions in cerebral vasomotor reactivity during the 4-year longitudinal study. Positive linear correlations were apparent between initial steady-state mean bihemisphere gray matter CBF levels and degrees of vasomotor reactivity, suggesting that the Law of Initial Value plays an important role. This should be borne in mind when analyzing scores of cerebral vasomotor reactivity. In the present communication, analysis of covariance was used to correct for influences of initial CBF levels on vasomotor responses tested while breathing pure oxygen.
Alternative Statistical Models for the Examination of Clinical Positron Emission Tomography/Fluorodeoxyglucose Data
Authors: Clark C. , Carson R. , Kessler R. , Margolin R. , Buchsbaum M. , DeLisi L. , King C. , Cohen R.
Published: April 2011

This article describes a method for partitioning metabolic variability found in positron emission tomography/[18F]fluorodeoxyglucose studies. For the 15 subjects examined, 74.8% of the total metabolic variability could be ascribed to individual differences in global metabolic rate, whereas 15.8% of the total variability was consistent regional variation or pattern across subjects. Subsequently, the method of Q-component analysis is described for the identification of strong- and weak-pattern subjects. In addition, a standardization procedure that amplifies the observed pattern by removing systematic individual differences is described. Finally, the implications of these findings and methods for future and clinical studies are discussed.
Specific Ouabain Binding to Brain Microvessels and Choroid Plexus
Authors: Harik Sami I. , Doull Gregory H. , Dick Arthur P. K.
Published: April 2011

The energy-dependent transport of ions across the blood-brain barrier and the blood-cerebrospinal fluid barrier by Na+, K+-ATPase is credited with an important role in brain homeostasis. In this study, we have assessed the relative enrichment of Na+, K+-ATPase in regional brain capillary preparations and in the choroid plexus by the quantitative determination of the cardiac glycoside binding sites in these preparations using [3H]ouabain as a ligand. We find that ouabain binds specifically to brain microvessels of the rat and the pig and to the choroid plexus of the pig in a saturable manner. The maximum density of ouabain binding sites in brain microvessels of both species is about one-fourth that of the crude membranes of the cerebrum and cerebellum. The density of ouabain binding sites in the pig choroid plexus is intermediate between that of the brain and brain microvessels. We do not find regional differences in ouabain binding to membrane fractions of the cerebrum and cerebellum, nor any significant differences in ouabain binding to cerebral and cerebellar microvessels. These findings provide quantitative estimates of Na+, K+-ATPase in brain capillaries and choroid plexus.
Quantitation of Local Cerebral Blood Flow and Partition Coefficient without Arterial Sampling: Theory and Validation
Authors: Koeppe Robert A. , Holden James E. , Polcyn Robert E. , Nickles Robert J. , Hutchins Gary D. , Weese James L.
Published: April 2011

A new technique that requires neither arterial blood sampling nor prior knowledge of the indicator's tissue–blood partition coefficient has been developed for quantitation of local CBF. This technique arises from an existing method that uses the inert, freely diffusible gaseous tracer [18F]methyl fluoride (CH318F) and positron computed tomography. The shape of the arterial blood curve is derived from continuous sampling of expired air. The concentration of CH318F in the arterial blood is assumed to be proportional to the expired gas curve interpolated between end-tidal values. The absolute scale of the blood curve is determined by fitting a series of venous blood samples to a multicompartment model. Four validation studies were performed to compare values derived using the venous scaled expired breath input function with those derived using direct arterial samples. The proposed method gave higher flow values than the standard arterial sampling method by an average of 4.4%. These validation studies and data from both normal and patient scans suggest that the method provides the quantitation necessary for interstudy comparisons yet avoids the trauma of an arterial puncture.
Effect of Iodoacetate on Local Cerebral Blood Flow and Glucose Metabolism in Cats: A Double-Radionuclide Autoradiographic Study
Authors: Tanaka Kortaro , Jones Stephen C. , Dora Eors , Greenberg Joel H. , Reivich Martin
Published: April 2011

The effect of iodoacetate (IAA), an inhibitor of glycolysis, on local CBF (LCBF) and local CMRglu (LCMRglu) was studied in cats by means of a double-radionuclide autoradiographic method. Artificial CSF containing 5 m M IAA was superfused on the left parietal cortex under a cranial window for 30 min. [14C]2-Deoxyglucose and [123I]iodoantipyrine were injected for the determination of LCMRglu and LCBF, respectively. A marked increase in LCBF, accompanied by a moderate to severe depression of LCMRglu, was observed in the IAA-superfused cortex. This result suggests that LCBF may be closely regulated by the cellular energy state associated with glycolytic activity in brain tissue.
Effects of (D-Met2, Pro5)-Enkephalinamide and Naloxone on Pial Vessels in Cats
Authors: Kobari Masahiro , Gotoh Fumio , Fukuuchi Yasuo , Amano Takahiro , Suzuki Norihiro , Uematsu Daisuke , Obara Katsuyuki , Gogolak Ivan , Sándor Péter
Published: April 2011

To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (d-Met2, Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 ± 24.9 μm) were found to dilate after the intravenous administration of 1 mg/kg of (d-Met2, Pro5)-enkephalinamide, and a definite dilatation of 7.1–7.6% persisted for 15 min. Pial veins (100.6 ± 20.2 μm) also dilated but to a lesser degree. The MABP (118.7 ± 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 ± 17.2 μm) showed a slight but significant dilatation of 2.3–5.3%. There were no significant changes in pial veins (87.0 ± 12.4 μm). MABP (130.4 ± 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.
Ischemia-Induced Shift of Inhibitory and Excitatory Amino Acids from Intra- to Extracellular Compartments
Authors: Hagberg Henrik , Lehmann Anders , Sandberg Mats , Nyström Britta , Jacobson Ingemar , Hamberger Anders
Published: April 2011

Brain ischemia was induced for 10 or 30 min by clamping the common carotid arteries in rabbits whose vertebral arteries had previously been electrocauterized. EEG and tissue content of high energy phosphates were used to verify the ischemic state and to evaluate the degree of postischemic recovery. Extracellular levels and total contents of amino acids were followed in the hippocampus during ischemia and 4 h of recirculation. At the end of a 30-min ischemic period, GABA had increased 250 times, glutamate 160 times, and aspartate and taurine 30 times in the extracellular phase. The levels returned to normal within 30 min of reflow. A delayed increase of extracellular phosphoethanolamine and ethanolamine peaked after 1–2 h of reflow. Ten minutes of ischemia elicited considerably smaller but similar effects. With respect to total amino acids in the hippocampus, glutamate and aspartate decreased to 30–50% of control while GABA appeared unaffected after 4 h of reflow. Alanine, valine, phenylalanine, leucine, and isoleucine increased severalfold. The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, are considered in relation to the pathophysiology of neuronal cell loss during cerebral ischemia.
Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain
Authors: Kuschinsky W. , Suda S. , Sokoloff L.
Published: April 2011

The relationship between local cerebral glucose utilization (LCGU) and local CBF (LCBF) was examined during the action of γ-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.
Effect of Leukotrienes, 12-HETE, Histamine, Bradykinin, and 5-Hydroxytryptamine on in vivo Rabbit Cerebral Arteriolar Diameter
Authors: Kamitani Toshiharu , Little Marcia H. , Ellis Earl F.
Published: April 2011

To determine the possible role that leukotrienes (LTs) may play in the regulation of cerebral blood flow, the responses of cerebral arterioles to LTs and 12-hydroxyeicosatetraenoic acid (12-HETE) were studied in vivo in rabbits equipped with a cranial window for direct observation of the microcirculation. Topical application of LTC, LTD4, or 12-HETE (1.6 × 10−9–3.1 × 10−6 M) neither constricted nor dilated the pial arteries. LTB4 produced only a 5% vasoconstriction at 3.0 × 10−6 M. However, bradykinin induced dose-dependent arteriolar vasodilation and histamine and 5-hydroxytryptamine induced dose-dependent arteriolar vasoconstriction. Although some LTs have potent vasoconstrictor activity in peripheral tissues and 5-lipoxygenase products have been hypothesized to be mediators of vasospasm after subarachnoid hemorrhage, LTB4, LTC4, LTD4, and 12-HETE apparently are unable to induce significant constriction of the cerebral arterioles in the anesthetized rabbit.
What is the Correct Value for the Brain-Blood Partition Coefficient for Water?
Authors: Herscovitch Peter , Raichle Marcus E.
Published: April 2011

A knowledge of the brain-blood partition coefficient (γ) for water is usually required for the measurement of CBF with [15O]water. The currently accepted value for whole-brain Λ, 0.95–0.96 ml/g, calculated from brain and blood water content data, is incorrect because in the calculation, the blood water content was not adjusted for the density of blood. The correct value is 0.90 ml/g. Variations in brain or blood water content affect Λ. Thus, Λ changes during development of the brain and varies regionally in it, even among different gray matter structures, owing to variation in brain water content. In addition, Λ would be expected to vary with the hematocrit, owing to changes in blood water content. The impact of using an incorrect value for Λ will depend on the sensitivity of the CBF measurement technique used to errors in Λ.
Subarachnoid Hemorrhage in the Rat: Cerebral Blood Flow and Glucose Metabolism after Selective Lesions of the Catecholamine Systems in the Brainstem
Authors: Delgado Tia J. , Diemer Nils H. , Svendgaard Niels-Aage
Published: April 2011

A double-isotope autoradiographic technique was used to evaluate CBF and glucose metabolism 2 days after a subarachnoid hemorrhage (SAH) in rats with lesions in the lower brainstem. Lesioning in the mesencephalon of the ascending catecholamine pathways from locus ceruleus and from the A1 and A2 nuclei, or lesioning in the medulla oblongata of the ascending fibers from A1 and A2, prevents the development of the global changes in flow and metabolism seen in normal animals post SAH. Also the focal low-flow areas with markedly elevated deoxyglucose uptake, which can develop in normal animals 2 days post SAH, were not seen in the lesioned animals after the SAH. The findings indicate that the A1 and A2 nuclei, which project to the hypothalamus–pituitary, are essential for the flow and metabolic changes after an SAH. The lesions per se did not change baseline flow and metabolism as compared with sham-lesioned animals.
Effect of Vascular Activity in the Determination of Rate Constants for the Uptake of 18F-Labeled 2-Fluoro-2-Deoxy-D-Glucose: Error Analysis and Normal Values in Older Subjects
Authors: Evans A. C. , Diksic M. , Yamamoto Y. L. , Kato A. , Dagher A. , Redies C. , Hakim A.
Published: April 2011

Regional cerebral blood volume (CBV) can be calculated using data obtained during the kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) uptake measured by positron emission tomography (PET). As a result the influence of vascular activity upon the determination of FDG rate constants can be minimized. The method is investigated by simulation experiments and by analysis of PET studies on seven older, healthy human volunteers aged 52–70 years. The accuracy of measured FDG rate constants k1, k2, and k3, obtained either by omitting the early portion of the uptake curve or by explicit inclusion of CBV as a fit parameter, is compared. The root mean square error in measured rate constant for the latter method is equivalent to that obtained by omitting the first 2.5–3 min of tissue data and neglecting the CBV term. Hence, added information about the physiological state of the tissue is obtained without compromising the accuracy of the (FDG) rate constant measurement. In hyperemic tissue the explicit determination of the vascular fraction results in more accurate estimates of the FDG rate constants. The ratio of CBV determined by this method to CBV obtained using C15O in six subjects with CBV in the normal range was 0.92 ± 0.32. A comparison of the CBV image obtained by this method with that obtained using C15O in an arteriovenous malformation case demonstrates the accuracy of the approach over a wide range of CBV values. The mean value for CBV fraction in gray matter obtained by this method in the older control group was 0.040 ± 0.014. Average gray matter rate constants obtained were k1 = 0.084 ± 0.012, k2 = 0.150 ± 0.071, and k3 = 0.099 ± 0.045 min−1.
Correction of Positron Emission Tomography Data for Cerebral Atrophy
Authors: Herscovitch Peter , Auchus Alexander P. , Gado Mokhtar , Chi David , Raichle Marcus E.
Published: April 2011

Because positron emission tomography (PET) provides measurements per unit volume of intracranial contents, these measurements may be affected by the inclusion of metabolically inactive CSF spaces in the volume in which they are made. Thus, PET measurements of CBF and metabolism may be artifactually lowered in normal aging and dementia, which are both associated with significant brain atrophy. We describe a method to correct global PET data, averaged over several tomographic slices, for cerebral atrophy by using measurements of CSF space volume obtained with quantitative x-ray computed tomography. The importance of making such a correction is demonstrated using PET measurements of CBF and oxygen metabolism obtained in normal young, normal elderly, and demented subjects.
Reactivity of Rat Pial Arterioles and Venules to Adenosine and Carbon Dioxide: With Detailed Description of the Closed Cranial Window Technique in Rats
Authors: Morii Seiji , Ngai Al C. , Winn H. Richard
Published: April 2011

This study describes a closed cranial window technique that allows the observation and measurement of rat pial arterioles and venules in situ. The resolving power of this system is 1–2 μm. Using this sensitive technique, we characterized the responses to 7% carbon dioxide inhalation and adenosine in arterioles (10–70 μm) and venules (15–100 μm). During carbon dioxide inhalation, larger arterioles (>40μm) dilated more than smaller arterioles (<20 μm). There was limited vasoreac-tivity of pial venules during CO2 inhalation. Dilation of arterioles was initially observed with an adenosine concentration of 10−8 M. Almost a twofold increase in diameter was noted at 10−3 M. In contrast to the effect of CO2 inhalation, the degree of dilation with topical application of adenosine was not size dependent. Pial venules did not respond to adenosine. The technique for observation of pial vessels using the closed cranial window and for measurement of vessel diameter by video camera system microscopy is a powerful tool for studying in vivo the cerebral circulation in the rat.
Regional Cerebral Ischemia in the Gerbil: Measurement of Regional Cerebral Blood Flow by Quantitative Autoradiography
Authors: Yoshimine Toshiki , Hayakawa Toru , Yamada Kazuo , Takemoto Osamu , Kato Amami , Ushio Yukitaka , Mogami Heitaro
Published: April 2011

Alterations in the regional CBF after occlusion of the posterior communicating, middle cerebral, or common carotid artery were investigated in the gerbil with a quantitative autoradiographic technique using [14C]iodoantipyrine. Occlusion of the posterior communicating artery produced severe ischemia in the ipsilateral hippocampus, thalamus, and dorsal mesencephalon. Occlusion of the middle cerebral artery produced severe ischemia in the ipsilateral rostral and central cerebral cortex and lateral caudate–putamen. Occlusion of the common carotid artery produced ipsilateral hemispheric ischemia of variable degrees. The distribution and degree of cerebral ischemia produced by occlusion of one of these arteries correlated closely to the arterial territory and the extent of collateral blood supply. Since the areas affected after occlusion of the posterior communicating or middle cerebral artery differ, those models will be useful for the comparative investigation of the ischemia-related cerebral pathophysiology associated with different sites of primary lesion.
Triple-Tracer Autoradiography of Cerebral Blood Flow, Glucose Utilization, and Protein Synthesis in Rat Brain
Authors: Mies G. , Bodsch W. , Paschen W. , Hossmann K.-A.
Published: April 2011

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]deoxyclusively 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 Ultro-film 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.
Synthesis of Heat Shock Proteins in Rat Brain Cortex after Transient Ischemia
Authors: Dienel Gerald A. , Kiessling Marika , Jacewicz Michael , Pulsinelli William A.
Published: April 2011

Cell-free protein synthesis and two-dimensional gel autoradiography were used to characterize early postischemic protein synthesis in rat neocortex. Severe forebrain ischemia was induced for 30 min (four-vessel occlusion model) and followed by 3 h of recirculation. Polysomes were isolated from the cerebral cortex, translated in vitro in a reticulocyte system, and analyzed by two-dimensional gel electrophoresis. The translation products of postischemic polysomes included a major new protein family (70 kDa) with multiple isoelectric variants that was found to comigrate with the 68- to 70-kDa “heat shock” protein synthesized from polysomes of hyperthermic rats. Two other stress proteins (93 and 110 kDa) also appeared to be synthesized in increased amounts after ischemia. A complement of proteins that was indistinguishable from that of controls was also synthesized after ischemia, indicating that messenger ribonucleic acid coding for most brain proteins is preserved after ischemia and is bound to polysomes.
Effect of Theophylline on Ischemically Induced Hippocampal Damage in Mongolian Gerbils: A Behavioral and Histopathological Study
Authors: Rudolphi Karl A. , Keil Manfred , Hinze Heinz-Joachim
Published: April 2011

We investigated the influence of the adenosine antagonist theophylline on the degree of hippocampal cell damage in the Mongolian gerbil following brief periods of forebrain ischemia. Male gerbils were randomly divided into nine groups. Ten minutes before surgery, four groups, which were later subjected to 1, 2, 3, or 5 min of bilateral carotid occlusion under halothane anesthesia, received theophylline (30 mg/kg, p.o.). Four groups served as nontreated ischemic controls; the ninth group was used to measure theophylline serum concentration. Neurological symptoms were classified by using a behavioral score. Fourteen days after ischemia, the brains were removed, and the hippocampus was histologically examined “blind” for the degree of cell damage in the CA1 sector, which was expressed as a semiquantitative histopathological score. There were no behavioral or histological abnormalities in either the control or theophylline group with 1 min of ischemia. With increasing duration of ischemia, the neurological symptoms worsened and the number of necrotic pyramidal cells increased significantly. The pretreatment with theophylline only moderately aggravated the neurological symptoms, whereas it enhanced the ischemic cell damage significantly. The results are discussed with respect to recent findings that theophylline may block putatively protective effects of endogenous adenosine, whose concentration in the brain is known to rise significantly during ischemia.
Vasomotor Effects of Neurotransmitters and Modulators on Isolated Human Pial Veins
Authors: Hardebo Jan Erik , Kåhrström Jan , Owman Christer , Salford Leif G.
Published: April 2011

Vasomotor reactivity of human pial veins, obtained in conjunction with neurosurgical operations, was studied in vitro. The effect of transmitters in nerves previously recognized in these vessels, as well as that of neuromodulators, was characterized. A comparison of these effects with their effects in the nearby pial arteries of the same patients was made. It was found that the veins were equipped with more sensitive α-adrenergic receptors (lower EC50 values) than the arteries. The reverse was found for 5-hydroxytryptamine. Acetylcholine, which causes an endothelium-dependent dilation of pial arteries, contracted the veins despite an apparently intact endothelium. Considering the lower maximum values in veins, responses to histamine, the neuropeptides calcitonin gene-related peptide, bradykinin, and neuropeptide Y; and prostaglandins (PGE1 and PGF2α) were principally the same in the arteries and veins. The dilatory responses to vasoactive intestinal polypeptide and substance P were less pronounced in veins than in arteries. The veins only transiently contracted to a depolarizing potassium solution; calcium influx promotors and inhibitors, as well as calcium-free solution, did not affect the contractile ability of the vein, contrasting to the reactivity of the artery. This clearly indicates that the veins are not substantially dependent upon calcium influx for their acute contractile ability.