bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Single-Photon Emission Computed Tomography with [123I]Iodoamphetamine and Xenon-Enhanced Computed Tomography for Assessing Regional Cerebral Blood Flow
Authors: Hellman R. S. , Collier B. D. , Tikofsky R. S. , Kilgore D. P. , Daniels D. L. , Haughton V. M. , Walsh P. R. , Cusick J. F. , Saxena V. K. , Palmer D. W. , Isitman A. T.
Published: April 2011

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl- p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.
Loss of Striatal [76Br]Bromospiperone Binding Sites Demonstrated by Positron Tomography in Progressive Supranuclear Palsy
Authors: Baron J. C. , Mazière B. , Loc'h C. , Cambon H. , Sgouropoulos P. , Bonnet A. M. , Agid Y.
Published: April 2011

Using positron tomography and 76Br-labeled bromospiperone, a neuroleptic drug with high affinity for the dopamine (DA) receptors, we have estimated the specific binding of the radiotracer to striatal DA receptors in seven patients suffering from progressive supranuclear palsy. Compared with age- and sex-matched control subjects, we found a significant (p < 0.02) decrease of the striatum–cerebellum uptake ratio in progressive supranuclear palsy patients, suggesting loss of striatal DA receptors. This in vivo study confirms recent postmortem data on progressive supranuclear palsy patients and provides an explanation for the lack of benefit from l-DOPA and DA agonists in this condition, despite reduced nigrostriatal dopaminergic function.
Effects of Temporal Sampling, Glucose Metabolic Rates, and Disruptions of the Blood—Brain Barrier on the FDG Model with and without a Vascular Compartment: Studies in Human Brain Tumors with PET
Authors: Hawkins Randall A. , Phelps Michael E. , Huang Sung-Cheng
Published: April 2011

The addition of a cerebral blood volume (CBV) compartment in the [18F]2-fluoro-2-deoxy-d-glucose (FDG) model produces estimates of local CBV simultaneously with glucose metabolic rates when kinetic FDG studies are performed. We investigated the influence of this term upon CMRglc values in a series of brain tumor patients and found that significant overestimations of CMRglc are possible if the effect of CBV upon the model is ignored. The magnitude of this potential over-estimation is directly related to the absolute value of CBV locally and inversely related to the CMRglc value. The kinetic estimates also permitted an evaluation of the FDG model in an environment with a variable disruption of the blood–brain barrier. Incorporating the vascular compartment in the FDG model also frequently improved the statistical accuracy of model fits to tissue kinetic data. The sampling requirements for this model configuration were also investigated in a series of computer simulations.
Characterization of Experimental Ischemic Brain Edema Utilizing Proton Nuclear Magnetic Resonance Imaging
Authors: Kato Hiroyuki , Kogure Kyuya , Ohtomo Hitoshi , Izumiyama Masahiro , Tobita Muneshige , Matsui Shigeru , Yamamoto Etsuji , Kohno Hideki , Ikebe Yoshinori , Watanabe Takao
Published: April 2011

Correlations between T1 and T2 relaxation times and water and electrolyte content in the normal and ischemic rat and gerbil brains were studied by means of both nuclear magnetic resonance (NMR) spectroscopic and imaging methods. In the spectroscopic experiment on excised rat brains, T1 was linearly dependent on tissue water content and T2 was prolonged in edematous tissue to a greater extent than expected by an increase in water content, showing that T2 possesses a greater sensitivity for edema identification and localization. Changes in Na+ and K+ content of the tissue mattered little in the prolongation of relaxation times. Serial NMR imaging of gerbil brains insulted with permanent hemispheric ischemia offered early lesion detection in T1- and especially T2-weighted images (detection as soon as 30 min after insult). The progressive nature of lesions was also imaged. Calculated T1 and T2 relaxation times in regions of interest correlated excellently with tissue water content ( r = 0.892 and 0.744 for T1 and T2, respectively). As a result, detection of cerebral ischemia utilizing NMR imaging was strongly dependent on a change in tissue water content. The different nature of T1 and T2 relaxation times was also observed.
Calcium Antagonist (PY 108-068) Treatment May Further Decrease Flow in Ischemic Areas in Acute Stroke
Authors: Vorstrup S. , Andersen A. , Blegvad N. , Paulson O. B.
Published: April 2011

The effect of the possible influence of a new calcium antagonist, PY 108-068, on regional CBF was studied in patients suffering acute ischemic stroke. The dosage was 1.5 + 2.5 mg intravenously in six patients (series 1) and 2.5 + 5.0 mg intravenously in five other patients (series 2). CBF was measured before and after treatment by xenon-133 inhalation and single-photon emission computed tomography (Tomomatic 64). In the first series, no changes in hemispheric CBF, MABP, or clinical symptoms were noted after treatment, but one patient showed an increase of CBF in part of the periin-farct area. In the second series, slight increases in mean hemispheric flow values were seen, but in three of the five patients CBF decreased even further in the ischemic area. MABP decreased by 13%, and the clinical symptoms were unchanged.
Regional Cerebral Glucose Transport in Insulin-Dependent Diabetic Patients Studied Using [11C]3-O-Methyl-D-Glucose and Positron Emission Tomography
Authors: Brooks D. J. , Gibbs J. S. R. , Sharp P. , Herold S. , Turton D. R. , Luthra S. K. , Kohner E. M. , Bloom S. R. , Jones T.
Published: April 2011

Regional cerebral [11C]3- O-methyl-d-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 m M), and four were studied at hyperglycaemic plasma glucose levels (mean 13 m M). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 m M had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and d-glucose for the passive facilitated transport carrier system for hexoses across the blood–brain barrier (BBB). It is concluded that the number and affinity of d-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of d-glucose across the BBB.
Recovery of Monkey Brain after Prolonged Ischemia. II. Protein Synthesis and Morphological Alterations
Authors: Bodsch W. , Barbier A. , Oehmichen M. , Ophoff B. Grosse , Hossmann K.-A.
Published: April 2011

Recovery of protein synthesis following 1 h of complete ischemia of the monkey brain was assessed by 3H-labeled amino acid incorporation in vivo at various postischemic periods between 1.5 and 24 h. The regional autoradiographic patterns obtained were compared on the basis of precursor-product relationships determined biochemically at the end of the tracer incorporation studies. Shortly after ischemia, protein synthesis was severely inhibited, but it gradually recovered with increasing recirculation times. In the cerebellum it returned to almost normal levels within 3 h and in the cortex within 24 h. Hippocampal and thalamic regions, however, did not recover control levels of protein synthesis at 24 h. His-toautoradiographic evaluation of amino acid incorporation in individual neurons revealed recovery of pyramidal neurons in the CA1 and CA3 sectors of the hippocampus within 6 h of recirculation, which, however, was followed by secondary inhibition after longer recirculation. Neurons in cortical layer 5 steadily recovered to near control within 24 h, with the exception of those located in arterial border zones, which returned to only 50% of control at 24 h. Incomplete recovery was also observed in thalamic neurons and Purkinje cells. The regional and histoauto-radiographic pattern of protein synthesis correlated with the morphological appearance of cells. Ischemic cell changes (mainly of the dark type with microvacuolization and perineuronal glial swelling) were marked after short recirculation times but gradually disappeared in parallel with the return of protein synthesis in most regions of the brain. Only in pyramidal cells of the hippocampus, thalamic neurons, and Purkinje cells were changes not reversed during the observation period. The results obtained corroborate the electrophysiological observations reported in the first part of this investigation and support the notion that the majority of the neurons of monkey brain survive complete cerebrocirculatory arrest of 1 h for at least 1 day.
Insufficient Supply of Reducing Equivalents to the Respiratory Chain in Cerebral Cortex during Severe Insulin-Induced Hypoglycemia in Cats
Authors: Bryan Robert M. , Jöbsis Frans F.
Published: April 2011

The ability of endogenous substrates in brain to substitute for glucose as sources for energy metabolism during insulin-induced hypoglycemia was studied. The ratio of the arteriovenous difference of glucose to the arteriovenous difference of oxygen in the cerebral cortex was measured during progressive hypoglycemia in paralyzed, artificially ventilated cats that were anesthetized with pentobarbital sodium and nitrous oxide. The ratio did not change when blood glucose fell from a mean of 7.68 to ∼2 μmol/ml. Below 2 μmol/ml the ratio decreased, indicating that substrates other than the glucose supplied by the blood were being utilized. In another series of experiments, changes in the redox state of respiratory chain NAD were monitored from the cerebral cortex using microfluorometry during the onset of hypoglycemia and the recovery. Hypoglycemia severe enough to produce isoelectric EEG was accompanied by an oxidation of NADH, demonstrating that the supply of reducing equivalents to the respiratory chain was decreased. Recovery from hypoglycemia, produced by intravenous glucose injections, was accompanied by an increase in blood glucose concentrations, the return of EEG activity, and a decrease in the NAD/NADH ratio. When blood glucose concentration reached 2.23 during the recovery, further increases in blood glucose had no effect on the redox state of NAD. Although alternative substrates appear to be utilized for energy metabolism during severe hypoglycemia, they cannot fully replace glucose as the source of reducing equivalent to the respiratory chain.
Nimodipine and the Haemodynamic and Histopathological Consequences of Middle Cerebral Artery Occlusion in the Rat
Authors: Gotoh Osamu , Mohamed Awni A. , McCulloch James , Graham David I. , Harper A. Murray , Teasdale Graham M.
Published: April 2011

The effect of the administration of nimodipine (1 μg kg−1 min−1), initiated 5 min after occlusion of a middle cerebral artery (MCA), upon cerebral haemodynamics ([14C]iodoantipyrine autoradiography) and neuropathological outcome (volume of histologically ischaemic tissue) was investigated in anaesthetized rats. Measurements were made of the level of local CBF (LCBF) in a total of 37 neuroanatomically defined areas, either ipsilateral or contralateral to the occluded vessel, and the autoradiograms were examined using a new approach to quantitative densitometry that employed a frequency distribution analysis of the CBF in sections of the brain at different coronal planes. Both methods of analysis showed that nimodipine, administered after the ischaemic event, did not modify the pattern of CBF distribution after MCA occlusion. The extent of ischaemic brain damage was determined by histological examination. There was no evidence that the extent of ischaemic damage, either in sections at eight different coronal planes or in overall volume, was significantly different in animals that received nimodipine from that observed in animals that received only the vehicle used to dissolve the drug. The lack of cerebral circulatory and neuropathological alterations when nimodipine administration is initiated after occlusion of the MCA is contrasted with the higher levels of LCBF and the reductions in the volume of ischaemic tissue that were found when nimodipine was administered before occlusion of the artery.
Delayed Treatment with Nimodipine Improves Cerebral Blood Flow after Complete Cerebral Ischemia in the Dog
Authors: Milde Leslie Newberg , Milde James H. , Michenfelder John D.
Published: April 2011

Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 μg kg−1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 μg kg−1 min−1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min−1 100 g−1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min−1 100 g−1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min−1 100 g−1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.
Quantitative Measurement of Cerebral Blood Flow and Cerebral Blood Volume after Cerebral Ischaemia
Authors: Todd Nicholas V. , Picozzi Piero , Crockard H. Alan
Published: April 2011

CBF obtained by the hydrogen clearance technique and cerebral blood volume (CBV) calculated from the [14C]dextran space were measured in three groups of rats subjected to temporary four-vessel occlusion to produce 15 min of ischaemia, followed by 60 min of reperfusion. In the control animals, mean CBF was 93 ± 6 ml 100 g−1 min−1, which fell to 5.5 ± 0.5 ml 100 g−1 min−1 during ischaemia. There was a marked early postischaemic hyperaemia (262 ± 18 ml 100g−1 min−1), but 1 h after the onset of ischaemia, there was a significant hypoperfusion (51 ± 3 ml 100 g−1 min−1). Mean cortical dextran space was 1.58 ± 0.09 ml 100 g−1 prior to ischaemia. Early in reperfusion there was a significant increase in CBV (1.85 ± 0.24 ml 100 g−1) with a decrease during the period of hypoperfusion (1.33 ± 0.03 ml 100 g−1). Therefore, following a period of temporary ischaemia, there are commensurate changes in CBF and CBV, and alterations in the permeability–surface area product at this time may be due to variations in surface area and not necessarily permeability.
Cerebral Protein Synthesis during Long-Term Recovery from Severe Hypoglycemia
Authors: Kiessling Marika , Auer Roland N. , Kleihues Paul , Siesjö Bo K.
Published: April 2011

Regional protein synthesis was investigated in the rat brain during long-term recovery from insulin-induced hypoglycemia with 30 min of cerebral electrical silence. At various time intervals up to 14 days after glucose replenishment, animals received a single dose of L-[3, 5-3H]tyrosine and were killed 30 min later. Brains were processed for autoradiography using the stripping film technique. Although hypoglycemia sufficiently severe to cause cessation of EEG activity leads to almost complete inhibition of amino acid incorporation in all “vulnerable” forebrain structures (cerebral cortex, hippocampus, caudoputamen), autoradiographs revealed a very specialized sequence with differential posthypoglycemic restoration of biosynthetic activity in certain neuronal cell types. Three major subpopulations could be distinguished: Neurons that fully regained their protein synthetic capacity within 6 h following hypoglycemia (cortical neurons of layer III–VI, large neurons in the caudoputamen, CA3 and CA4 pyramidal neurons, the majority of granule cells of the dentate gyrus) seemed to escape neuronal necrosis. Prolonged impairment of protein synthesis with only partial restoration during the early posthypoglycemic recovery period (CA1 neurons, most small- to medium-sized neurons of the caudoputamen) carried an increased risk of permanent cell damage. The large majority of these neurons, however, showed full recovery of protein synthesis as late as 7 days after hypoglycemia. Neurons with complete lack of amino acid incorporation after 6 h of recovery (granule cells at the crest of the dentate gyrus, small neurons of the dorsolateral caudoputamen) never resumed protein synthesis, regressed, and died. These studies in conjunction with morphological analysis indicate that the sequential recovery of protein synthesis reflects the extent to which neuronal populations are at risk during severe hypoglycemia.
Effects of Clonidine on Cerebral Blood Flow and the Response to Arterial CO2
Authors: Kanawati Isa S. , Yaksh Tony L. , Anderson Robert E. , Marsh Richard W.
Published: April 2011

CBF, as measured by the clearance of 133Xe or 85Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the Paco2 is elevated over a range of 20–60 mm Hg (slope Xe, 1.65 ± 0.14 ml/100 g/min/mm Hg; slope Kr, 1.40 ± 0.11 ml/100 g/min/mm Hg). Clonidine (20 μg/kg i.v.), a centrally acting, α2-preferring agonist, reduced the slope of the Paco2-CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood–brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated Paco2. Reduction in the MABP response to Paco2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the Paco2-MABP response observed in the absence of clonidine, a comparable reduction in the slope of the Paco2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of α2-receptors on the CBF-CO2 response cannot be attributed to an altered perfusion pressure.
Chronic Dexamethasone Pretreatment Aggravates Ischemic Neuronal Necrosis
Authors: Koide Tohru , Wieloch Tadeusz W. , Siesjö Bo K.
Published: April 2011

This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.
Focal Ischemia of the Rat Brain: Autoradiographic Determination of Cerebral Glucose Utilization, Glucose Content, and Blood Flow
Authors: Nedergaard Maiken , Gjedde Albert , Diemer Nils Henrik
Published: April 2011

Focal cerebral ischemia was induced in rats by occlusion of the middle cerebral artery. By a triple-tracer technique, cerebral glucose utilization, glucose content, and blood flow were simultaneously determined. Computer-assisted autoradiography revealed a core of dense ischemia in the lateral two-thirds of the striatum. A border zone of increased 2-deoxy-d-glucose (DG) uptake surrounded the ischemic insult in the acute stage. The lumped constant was increased only moderately in the border zone. Therefore, the enhanced DG uptake reflected increased glucose consumption. CBF was reduced to 20–30% in the cortical border, while minor depression and in some animals hyperemia were evident in the striate border. Six hours after the insult, the border zones of increased glucose consumption had disappeared in half the animals. In no animals examined after 20 h was glucose consumption enhanced. The study indicated a stable metabolic response to a reproducible focal insult. We conclude that continued enhancement of glucose consumption in marginally perfused areas indicates neuronal damage.
In vivo Measurement of Regional Brain and Tumor pH Using [14C]Dimethyloxazolidinedione and Quantitative Autoradiography. II: Characterization of the Extracellular Fluid Compartment Using pH-Sensitive Microelectrodes and [14C]Sucrose
Authors: Arnold James B. , Kraig Richard P. , Rottenberg David A.
Published: April 2011

We measured the extracellular (interstitial) pH (pHe) of RG-2 rat gliomas using H+-sensitive microelectrodes and estimated the volume of tumor extracellular space based on the tissue-plasma ratio of [14C]sucrose. The average RG-2 pHe was 7.63 ± 0.15 (mean ± SD, n = 6), whereas the average pHe of contralateral brain tissue was 7.34 ± 0.10 (n = 3) and arterial pH was 7.36 ± 0.02. RG-2 extracellular space water volume was estimated to be 0.3 ml water/g tissue. In separate experiments in normal, nontumored rats, intracellular pH (pHi) was calculated for nine gray and white matter regions based on measurements of tissue and plasma [14C]dimethyloxazolidinedione concentration. pHi values ranged from 6.80 to 6.94, and no consistent gray–white differences were observed. Our data suggest that tumor pHi is not more acidic than that of normal brain tissue and that the observed alkalinity of primary brain tumors is due to the presence of a large alkaline extracellular space.
Adenosine Receptors of Cerebral Microvessels and Choroid Plexus
Authors: Kalaria Rajesh N. , Harik Sami I.
Published: April 2011

We studied, by ligand binding methods, the two adenosine receptors, A, and A2, in rat and pig cerebral microvessels and pig choroid plexus. Ligand binding to cerebral microvessels was compared with that to membranes of the cerebral cortex. [3H]Cyclohexyladenosine and [3H]l-phenylisopropyladenosine were the ligands used for A1-receptors, and [3H]5'- N-ethylcarboxamide adenosine ([3H]NECA) was used to assess A2-receptors. We report that cerebral microvessels and choroid plexus exhibit specific [3H]NECA binding, but have no appreciable A1-receptor ligand binding sites. Specific binding of [3H]NECA to cerebral microvessels, choroid plexus, and cerebral cortex was saturable and suggested the existence of two classes of A2-receptor sites: high-affinity ( Kd ∼ 250 n M) and low-affinity ( Kd ∼ 1–2 μ M) sites. The Kd and Bmax of NECA binding to cerebral microvessels and cerebral cortex were similar within each species. Our results, indicating the existence of A2-receptors in cerebral microvessels, are consistent with results of increased adenylate cyclase activity by adenosine and some of its analogues in these microvessels.
Examination of the Blood-to-Brain Transfer of α-Aminoisobutyric Acid and Horseradish Peroxidase: Regional Alterations in Blood—Brain Barrier Function following Acute Hypertension
Authors: Ellison Mary D. , Povlishock John T. , Hayes Ronald L.
Published: April 2011

Blood–brain barrier (BBB) alterations following acute hypertension were studied in rats, employing as tracers in each animal both horseradish peroxidase (HRP) (MW 40,000) and [14C]α-aminoisobutyric acid ([14C]AIB) (MW 104). Eighteen animals were subjected to acute hypertension induced by the intravenous infusion of norepinephrine bitartrate (NE) (Levophed). Five animals injected with both tracers but not infused with NE served as controls. The brain of each animal was serially sectioned with adjacent sections processed either for macroautoradiography or for light microscopic visualization of HRP reaction product via histochemical reaction with tetramethylbenzidine. Quantitative blood-to-brain transfer constants for AIB were determined in each of 14 brain regions. Qualitative comparisons were also made between the AIB and HRP blood-to-brain extravasation patterns in each group. Acute hypertension increased cerebrovascular permeability to both AIB and HRP in most animals. Topographically, the sites of the most highly elevated AIB transfer corresponded with sites of HRP extravasation. Conversely, all sites of protein passage corresponded spatially to sites of elevated AIB transfer. Brain regions commonly showing increased permeability to both tracers included the cerebral cortices, corpus callosum, and thalamus. Importantly, some brain regions showed elevated AIB transfer constants where protein extravasation was absent. These regions included the caudate–putamen, hippocampus, basal forebrain, and cerebellum. These observations suggest that following acute hypertension, alterations in BBB permeability are not limited to vascular segments allowing protein extravasation.
Hydrogen Clearance Method for Determining Local Cerebral Blood Flow. I. Spatial Resolution
Authors: von Kummer Rüdiger , Herold Sigrid
Published: April 2011

To define the effective spatial resolution of the hydrogen clearance method, serial local CBF (LCBF) measurements were performed at different distances from the cortico–white matter junction of the cat brain. Twenty-five platinum-wire microelectrodes with a sensitive surface of 0.07 mm2 were inserted into the cerebral cortex of three cats through burr holes in the skull and advanced toward the ear-to-ear level in 1- or 0.1-mm steps. Most electrodes passed from high-perfusion regions into low-perfusion areas, indicating that the cortico–white matter junction had been traversed. Whereas within the gray and white matter the LCBF values were fairly constant, a striking decrease of CBF was registered at the cortico–white matter junction. Here the mean LCBF from 12 electrodes showed significant differences in flow between two locations 1 mm apart. On two occasions, a significant difference in CBF was found for locations only 0.1 mm apart. Despite this high spatial resolution, monoexponential clearance curves were detected only in the vicinity of the cortico–white matter junction. It is therefore assumed that factors other than flow might influence H2 clearance.
Hydrogen Clearance Method for Determining Local Cerebral Blood Flow. II. Effect of Heterogeneity in Cerebral Blood Flow
Authors: von Kummer Rüdiger , von Kries Friedrich , Herold Sigrid
Published: April 2011

The time course of hydrogen uptake and washout was followed simultaneously in extracranial arterial blood, cortex, subcortical white matter, and caudate nucleus of the cat brain to study intercompartmental hydrogen concentration differences. A clear delay of 1–2 min was seen between the onsets of concentration increase in arterial blood and low-flow brain tissues. Equilibration time was dependent on local CBF and varied between 3 and 34 min. Hydrogen was not cleared simultaneously from the regions under detection. This led to considerable concentration differences within the cerebral tissue during washin and washout phases. Analysis of the clearance curves revealed that secondary equilibration occurs during washout. Hydrogen concentration in the external carotid artery was not a reliable reflection of tracer input in the brain tissues. The consequences of these observations for other techniques of CBF measurement using less diffusive gases and external detection are discussed.
Comparison of the Inhibitory Effects of Antithrombin III, α2-Macroglobulin, and Thrombin in Human Basilar Arteries: Relevance to Cerebral Vasospasm
Authors: White Richard P.
Published: April 2011

Isolated human basilar arteries were used in this study to evaluate the inhibitory effect of antithrombin III (AT III), thrombin, and α2-macroglobulin (α2-M) on contractions elicited by K+, serotonin (5-HT), prostaglandin (PG) D2, PGF2α, and plasmin. α2-M (0.5–1.0 mg/ml) failed to affect the contractions produced by contractile agonists significantly but did notably reduce the basal tone of the arteries. Thrombin (1 and 10 U/ml) reduced basal tone and significantly inhibited the contractions elicited by K+, PGF2α, and plasmin. The relaxant effect of thrombin was abolished by procedures that destroy endothelium and by exposing the artery to thrombin for prolonged periods (tachyphylaxis). AT III (1–6 U/ml) reduced basal tone and significantly inhibited, in a concentration-dependent manner, the contractile responses to K+, 5-HT, PGD2, PGF2α, and plasmin. In sharp contrast to thrombin, AT III did not induce tachyphylaxis nor was its vasorelaxant effect significantly reduced by destruction of the endothelium. The results show AT III to be a potent and nonspecific inhibitor of human cerebral arteries and support the hypothesis that AT III may contribute to the delay of cerebral vasospasm seen in patients who experience aneurysmal hemorrhage.
Intracellular and Extracellular Spaces of Normal Adult Rat Brain Determined from the Proton Nuclear Magnetic Resonance Relaxation Times
Authors: Haida Munetaka , Yamamoto Masahiro , Matsumura Hideshi , Shinohara Yukito , Fukuzaki Minoru
Published: April 2011

The nuclear magnetic resonance method was used to investigate the state of water molecules in normal rat brain tissue in vitro. The transverse magnetization decay curve (TMDC) of the fresh brain tissue of adult rats (8- or 10-weeks-old) was biexponential, which could be interpreted in terms of two distinct transverse relaxation times ( T2). Several factors that may affect the TMDC are discussed. It was concluded that the fast and slow components of T2 correspond to those of the water molecules of the intracellular and the extracellular spaces of normal rat brain tissue, respectively.
pH, K+, and PO2 of the Extracellular Space during Ischaemia of Primate Cerebral Cortex
Authors: Harris R. J. , Richards P. G. , Symon L. , Habib A.-H.A. , Rosenstein J.
Published: April 2011

pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g−1 min−1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g−1 min−1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g−1 min−1, below which K+ rose rapidly. pHe and log K+ were linearly related and confirmed that pH fell by 0.3 U before K+ rose significantly, and fell by 0.6 U before the massive rise in K+. The mechanisms involved in this sequence of events and the role of pH changes in the development of the so-called “ischaemic penumbra” are discussed.
Effect of Adenosine on Human Cerebral Blood Flow as Determined by Positron Emission Tomography
Authors: Sollevi Alf , Ericson Kaj , Eriksson Lars , Lindqvist Christer , Lagerkranser Michael , Stone-Elander Sharon
Published: April 2011

The effect of intravenous infusion of adenosine on CBF was studied in seven patients with cerebral arteriovenous malformation. The patients were examined with positron emission tomography with controlled ventilation using [15O] water and [11C] fluoromethane as tracers. Total and regional CBF were determined before and during infusion of adenosine at rates producing a reduction of the MABP by ∼10–40%. Six patients were normoventilated, and one was hyperventilated. Mean CBF in areas with normal brain tissue was 54 ml/100 g/min before adenosine infusion under normoventilation. Adenosine infusion increased mean CBF with 23–85%. Mean CVR was decreased with 43–65% and exceeded the percentage reduction of MABP in all normoventilated subjects. In the hyperventilated patient, the reduction of CVR was similar to the reduction of MABP, and CBF was unaffected, except for a 30% increase in the thalamus. It is concluded that intravenous administration of adenosine produces marked cerebral vasodilation in normoventilated subjects and that this response can be counteracted by hyperventilation.
Calcium Accumulation and Neuronal Damage in the Rat Hippocampus following Cerebral Ischemia
Authors: Deshpande J. K. , Siesjö B. K. , Wieloch T.
Published: April 2011

The present study was undertaken to correlate calcium accumulation with the development of neuronal necrosis following transient ischemia. After 10 min of forebrain ischemia in the rat—a period that leads to reproducible damage of CA1 pyramidal cells—determination of calcium concentration and evaluation of morphological signs of cell body necrosis in the dorsal hippocampus were performed at various recirculation times. Tissue calcium concentration was not different from control at the end of ischemic period and did not change after 3, 6, 12, or 24 h of recirculation. However, after 48 h, calcium content increased significantly, with a further increase being seen after 72 h. At early recovery periods, only scattered necrotic neurons were observed. after 48 h, only 2 of 12 hemispheres showed more than 25 necrotic cells per section. More conspicuous neuronal death was observed after 72 h. The results thus demonstrate that net accumulation of calcium in regio superior of the hippocampus precedes marked necrosis of CA1 pyramidal cells. The results suggest that one primary event in the delayed death of these cells is membrane dysfunction with increased calcium cycling.
Ketamine Effects on Local Cerebral Blood Flow and Metabolism in the Rat
Authors: Cavazzuti Milena , Porro Carlo A. , Biral Gian Paolo , Benassi Carlo , Barbieri Gian Carlo
Published: April 2011

The effects of an anesthetic dose (100 mg/kg) of ketamine, a phencyclidine derivative, on local rates of cerebral glucose utilization (LCGU) and CBF (LCBF) have been investigated by the quantitative [14C]2-deoxyglucose and [14C]iodoantipyrine techniques in the unparalyzed, spontaneously breathing rat. In ketamine-injected animals, LCGU was significantly increased in some limbic structures and decreased in inferior colliculus, vestibular, and cerebellar nuclei. The degree and spatial distribution of drug-induced changes was similar for local blood flow rates, LCBF being increased in limbic regions and decreased in the inferior colliculus. Although PaCO2 values were higher in anesthetized animals, the pattern of LCBF/LCGU ratios was not significantly affected by ketamine in the 36 brain regions examined in this study. So, at least in the rat and at the anesthetic level studied here, a net vasodilatory in vivo effect was not observed. These results support the hypothesis that CBF changes induced by the drug in animals and man are primarily related to the metabolic effects exerted by ketamine on cerebral structures.
A Modification of the Method for the Measurement of Cerebral Blood Flow Using [14C]Iodoantipyrine in Small Animals
Authors: Richards H. K. , Lovick A. H. J. , Pickard J. D.
Published: April 2011

We have modified the method for the measurement of cerebral blood flow using [14C]iodoantipyrine in small animals to overcome problems caused by rapid sequential arterial sampling. A second isotope, gamma-emitting [99mTc]pertechnetate, is infused together with [14C]iodoantipyrine. The 99mTc is counted externally by a detector placed over the chest. The arterial curve for [14C]iodoantipyrine can be reconstructed from a single arterial sample collected from the severed neck and the shape of the 99mTc chest curve. Because of the short half-life of 99mTc (6 h), all 14C measurements, including preparation of autoradiograms, may be made 3 days later.
A Study of the Single Compartment Tracer Kinetic Model for the Measurement of Local Cerebral Blood Flow Using 15O-Water and Positron Emission Tomography
Authors: Gambhir Sanjiv S. , Huang Sung-Cheng , Hawkins Randall A. , Phelps Michael E.
Published: April 2011

The effects of varying the data collection time on the calculation of cerebral blood flow and distribution volume via the integrated projection technique were studied in four human subjects. The significance of these results in terms of the limitations of the single compartment model for 15O-water was explored using computer simulations. The simulations helped to account for causes for the variations seen in blood flow and distribution volume as a function of the data collection time. Two different compartmental models were explored for better quantitation of blood flow and distribution volume.
Topography of Capillary Density, Glucose Metabolism, and Microvascular Function within the Rat Inferior Colliculus
Authors: Gross Paul M. , Sposito Nadine M. , Pettersen Susan E. , Panton Diane G. , Fenstermacher Joseph D.
Published: April 2011

A midbrain nucleus of the auditory system, the inferior colliculus, was used as a model for analyzing spatial correlations or “coupling” among capillary density, tissue glucose metabolism, and several measures of microvascular function in the rat. The capillary bed of the inferior colliculus was examined with stereological techniques, and physiological measures were obtained with radioactive tracers, quantitative autoradiography, and image processing. Within the colliculus, capillary density, volume fraction, length, and surface area were highest in the central nucleus where the packing densities of neuropil and perikarya are greatest. Rates of glucose metabolism and blood flow correlated closely with capillary density in a 3 × 2 matrix of collicular subregions in the sagittal and coronal planes. The strength of this correlation suggests that estimates of capillary density can be made from measurements of tissue glucose metabolism within this structure under normal conditions. Microvascular blood volume and transcapillary flux of a neutral amino acid, α-aminoisobutyric acid, were homogeneous throughout the colliculus. The studies demonstrate quantitatively in a single brain nucleus a close correspondence between cytoarchitecture, richness of the capillary bed, and complexity of neural activity (inferred from local measures of glucose metabolism and blood flow). Such relationships were suggested by Craigie 67 years ago.
Measurement of Glucose Utilisation with [18F]2-Fluoro-2-Deoxy-D-Glucose: A Comparison of Different Analytical Methods
Authors: Lammertsma Adriaan A. , Brooks David J. , Frackowiak Richard S. J. , Beaney Ronald P. , Herold Sigrid , Heather Jon D. , Palmer Anthony J. , Jones Terry
Published: April 2011

A number of different analytical methods were applied to dynamic scans obtained with [18F]2-fluoro-2-deoxy-d-glucose and positron emission tomography. In particular, methods applying three, four, standard, or no rate constants were compared in four studies on three normal subjects. In addition, regional cerebral blood flow, oxygen utilisation, and blood volume were measured using the oxygen-15 steady-state inhalation technique. There was a large difference between values of glucose utilisation obtained with the various analytical methods, in particular between methods using three or four rate constants. This difference was not due to contamination of the tracer with [18F]2-fluoro-2-deoxy-d-mannose. For dynamic techniques, the separate measurement of regional cerebral blood volume was essential. Static techniques (single scans with standard or no rate constants) were best related to dynamic techniques utilising four rate constants. From the results, it followed, however, that these static techniques can only be applied clinically if relatively large disturbances of glucose metabolism and no changes in rate constants are anticipated. The lumped constant was assessed from the combined measurement of oxygen and glucose utilisation and was higher than previously reported.
Effect of Selective Lesions of Medullary Catecholamine Nuclei on Experimental Cerebral Vasospasm in the Rat
Authors: Svendgaard N. Aa. , Arbab M. A.-R. , Delgado T. J. , Rosengren E.
Published: April 2011

Intracisternal injection of blood in the rat induces an angiographically demonstrable, biphasic cerebral vasospasm of the vertebrobasilar system, with a maximal acute spasm at 10 min and a maximal late spasm at 2 days after the subarachnoid hemorrhage (SAH). Selective lesioning of the A1 nuclei in the medulla oblongata prior to the SAH prevents the development of the late spasm, but the acute spasm develops to the same extent as in sham-lesioned animals. Lesions of the medullary A2 nuclei not only prevent the development of both acute and late spasm, but give rise to a dilatation of the vertebrobasilar arteries at day 2 post-SAH. The study indicates that both the A1 and A2 nuclei participate in the development of vasospasm post-SAH. The contrasting patterns of spasm after A1 and A2 lesions suggest a different mechanism for acute and late spasm.
Acute Cerebral Ischaemia: Concurrent Changes in Cerebral Blood Flow, Energy Metabolites, pH, and Lactate Measured with Hydrogen Clearance and 31P and 1H Nuclear Magnetic Resonance Spectroscopy. I. Methodology
Authors: Gadian David G. , Frackowiak Richard S. J. , Crockard H. Alan , Proctor Edward , Allen Kathryn , Williams Stephen R. , Russell Ralph W. Ross
Published: April 2011

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. The NMR measurements were made with two surface coils, one on each hemisphere. This article describes the experimental details and shows that in acute unilateral or bilateral forebrain ischaemia metabolic changes can be monitored by NMR with no significant interhemispheric cross talk. The metabolic effects of reperfusion are also shown. The model allows the definition of the time course of the metabolic consequences of regional ischaemia and reperfusion in individual laboratory animals.
Regional Cerebral Blood Flow and Focal Cortical Perfusion: A Comparative Study of 133Xe, 85Kr, and Umbelliferone as Diffusible Indicators
Authors: Anderson Robert E. , Sundt Thoralf M. , Yaksh Tony L.
Published: April 2011

We report that regional CBF determined by the initial slope technique using 133Xe and 85Kr in cats and rabbits can be significantly influenced by the size of the field of measurement. The clearance curves of umbelliferone, a lipid-soluble intracellular pH fluorescent indicator, from a visually avascular 80-fm field were used to cross-correlate rCBF with focal cortical perfusion. Our findings indicate that in the cat, as the gamma or beta detector's field of volume was reduced, regional CBF (rCBF) measured by intraarterially injected 133Xe or 85Kr decreased in value by 33% and 28%, respectively, and the slope of the rCBF-Paco2 response curve became less steep by 56% and 45%, respectively. Umbelliferone, measuring a much smaller volume of tissue, showed a lower normocapnic flow and a more oblique Paco2 response curve. In the rabbits studied, the normocarbic rCBFs and the rCBF-Paco2 response curves measured with the three techniques corresponded to those measured in the cat. These results suggest that large field/volume measurements assess a measure of flow that is a weighted average of several distinct flow compartments and that these compartments differ in their response to changes in Paco2.
Frontal Blood Flow Changes in Recovery from Coma
Authors: Deutsch Georg , Eisenberg Howard M.
Published: April 2011

Two-dimensional studies of cortical blood flow were conducted in 20 closed head injury patients in a comatose state and subsequently in 9 patients as they recovered to an awake and responding state. Comatose patients showed a reduction of frontal flow compared to the resting pattern observed in age matched normal volunteers. In most patients the normal anterior-to-posterior flow gradient was reversed. Increases in global flow, while in coma, tended to exaggerate this reversal. Patients who survived showed a normalization of the regional flow pattern as they regained consciousness. The marked reduction of frontal blood flow in the comatose state was independent of locus of injury as determined by computed tomography (CT) scan data. Combined with previous CBF studies of sensory and cognitive activation, these findings suggest that frontal reduction may be a nonspecific effect of any state or condition involving reduced directed mental activity. This, in turn, raises questions about recent interpretations offered for frontal CBF reduction in psychiatric disease.