bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Measurement of Blood—Brain Barrier Permeability Using Rubidium-82 and Positron Emission Tomography
Authors: Brooks David J. , Beaney Ronald P. , Lammertsma Adriaan A. , Leenders Klaus L. , Horlock Peter L. , Kensett Malcolm J. , Marshall John , Thomas David G. , Jones Terry
Published: April 2011

In normal brain, the blood–brain barrier (BBB) is highly impermeable to K+ cations, their transport being controlled by ATPases situated in the endothelial cell membranes. 82Rb+ is a positron-emitting analogue of K+ with a half-life of 75 s. Using a steady-state model and positron emission tomography, quantitative extraction data for 82Rb+ transport across the BBB have been obtained both in normal human subjects and in a variety of conditions of cerebral pathology. A mean cerebral Rb extraction of 2.1% was found for normal subjects, corresponding to a mean value of 1.1 × 10−6 cm s−1 for 82Rb+ cation permeability across the BBB. No increase in cerebral Rb extraction was observed for patients with diffusely raised intracranial pressure secondary to obstructive hydrocephalus and benign intracranial hypertension, or for patients with multiple sclerosis or cerebral systemic lupus erythematosus. Cerebral tumours that were enhanced on computed tomography scanning showed a significant increase in local Rb uptake. No correlation between tumour size, or grade of glioma, and tumour Rb extraction was found. Nonenhancing tumours showed no increase in local Rb extraction, and regions of perifocal tumour oedema also had Rb extraction values in the normal range. It is concluded that increased Rb extraction occurs only where tight junction integrity in the BBB breaks down locally, that is, in the microcirculation of enhancing tumours but not in that of perifocal regions of tumour oedema or nonenhancing tumours.
An Improved Approach for Measurement of Regional Cerebral Rate Constants in the Deoxyglucose Method with Positron Emission Tomography
Authors: Kato Amami , Diksic Mirko , Yamamoto Y. Lucas , Strother Stephen C. , Feindel William
Published: April 2011

A new experimental approach was designed to measure regional rate constants for [18F]2-fluoro-2-d-deoxyglucose in the three-compartment model. A programmed infusion was used to keep the plasma tracer concentration constant for the first 20 min. Positron emission tomography images of the brain were taken every minute for 20 min in a low-resolution mode, then every 15–20 min for 2–3 h in a medium-resolution mode. Two simplified operational equations for the calculation of the regional rate constants were derived that incorporated the contribution of the vascular compartment to tissue activity. The first equation was applied to data collected during the initial 20 min (when the concentration of plasma tracer was constant) to estimate the values of k*1, k*2 , k*3, and the fraction of the vascular compartment. The second equation was applied to data collected during the whole experimental period to find the value of k*4 and to provide a better estimate of k*3. The regional rate constants measured experimentally in three dogs and a brain tumor patient agreed well with those in the literature. This method permits estimation of the local CMRglu under pathological conditions using regionally measured rate constants and provides new information on the pathophysiological meaning of the rate constants.
Effects of Anoxia on Cerebral Blood Flow in the Rat Brain: Evidence for a Role of Adenosine in Autoregulation
Authors: Phillis J. W. , Preston G. , DeLong R. E.
Published: April 2011

The purpose of these experiments was to determine the utility of a new method for monitoring CBF using a venous outflow technique with an extracorporeal circulation and to examine the effects of agents that potentiate or antagonize the actions of adenosine on the blood flow response to brief periods of anoxia. The results demonstrate the ability of the new technique to detect the increases in CBF in response to anoxia. Caffeine, an adenosine antagonist, reduced the intensity and duration of the anoxia-induced hyperemia. Dipyridamole and papaverine, inhibitors of adenosine uptake, potentiated the increase in CBF during anoxia. The results support the hypothesis that adenosine plays an important role in regulating CBF during anoxic episodes.
Spectrum of Altered Reactivity of Isolated Cerebral Arteries following Subarachnoid Haemorrhage—Response to Potassium, pH, Noradrenaline, 5-Hydroxytryptamine, and Sodium Loading
Authors: Pickard J. D. , Perry S.
Published: April 2011

The circular contractile responses to various stimuli have been measured in segments of cerebral arteries (both middle cerebral and basilar) taken from dogs either 3 or 7 days following the cisternal injection of autologous blood under anaesthesia. The maximum contractile response to 5-hydroxytryptamine was increased significantly 7 days following subarachnoid haemorrhage; the response to noradrenaline also increased but not significantly at 7 days. The contractile response to a raised extracellular potassium concentration (25 and 100 m M) was slightly depressed by 7 days, and the response to a fall in extracellular pH was depressed by 43% both 3 and 7 days following subarachnoid haemorrhage. The ability of these arteries to handle a sodium load was also assessed. The arteries were sodium loaded for various periods of time in mock cerebrospinal fluid with a zero potassium concentration. On transfer to 25 m M potassium solution, the duration but not the magnitude of the initial relaxation phase prior to a final contraction was greater with increasing time spent in the zero potassium solution. Both the magnitude and the duration of this relaxation phase, which reflect in part the ability of the vascular smooth muscle to extrude the sodium load, were increased in arteries following subarachnoid haemorrhage when compared with control arteries. These results demonstrate that the altered reactivity of cerebrovascular smooth muscle following subarachnoid haemorrhage persists in vitro and is more than simply an enhanced response to biogenic amines.
On the Construction of Functional Maps in Positron Emission Tomography
Authors: Blomqvist G.
Published: April 2011

A linear algorithm for the rapid calculation of local rate constants is proposed. The method is applicable to the three-compartment models currently used in the analysis of positron camera measurements with [11C]methionine, [11C]deoxyglucose, and [11C]glucose. The same technique can also be used for the regional measurement of local blood flow with the aid of a freely diffusible tracer. The algorithm was applied to measurements on humans with [11C]glucose. As a comparison, the same data were also analyzed with a standard nonlinear technqiue. Good agreement between the two methods was obtained.
Effects of Xenon and Krypton on Regional Cerebral Blood Flow in the Rat
Authors: Junck L. , Dhawan V. , Thaler H. T. , Rottenberg D. A.
Published: April 2011

The effects of high inspired concentrations of xenon and krypton on regional CBF (rCBF) were assessed in the rat using [14C]iodoantipyrine and quantitative autoradiography. Inhalation of 80% xenon for 1 or 2 min and inhalation of 40% xenon for 2 min were found to have significant effects on rCBF, including average increases of 75–96% in cerebral neocortical regions. Inhalation of 40% xenon for 1 min and of 80% krypton for 2 min had no significant effect on rCBF in most brain regions studied. If xenon inhalation produces effects on rCBF in humans similar to those observed in the rat, such effects could be an important source of error in xenon computed tomography rCBF studies.
Regional Multiparameter Estimation from Tomographic Diffusible Tracer Clearance Curves: Modification of the Double-Integral Method
Authors: Stokely Ernest M.
Published: April 2011

Measurement of regional CBF in transverse section using inert, diffusible tracers can be carried out using a double-integral form of the Kety-Schmidt equation. An implementation of this form proposed by Kanno and Lassen (the K-L estimator) is utilized by the Tomomatic 64, a dynamic single-photon computed tomography system that records washin-washout data during and following inhalation of 133Xe gas. Advantages of the algorithm include noninvasive calibration of the input function and excellent depiction of ischemia; disadvantages are sensitivity to errors in input function delay (δ), the inability to estimate the partition coefficient (Λ) (hence, only the clearance index, k, is estimated), and a noise sensitivity proportional to k. A modification of the method is proposed that not only accounts for δ variations, but also provides an estimate of relative Λ (hence, the perfusion, f, is estimated). The proposed estimator is shown to be robust in the presence of noise with error variances equal to or better than those with the K-L estimator, yet estimates of both relative f and Λ are provided by the modification. New simulation results implicate the Compton scatter fraction as a major contributor in the overestimation of white matter perfusion values using both the K-L and proposed estimators, and illustrate the need for hardware and software scatter fraction reduction and control.
Comparative Regional Analysis of 2-Fluorodeoxyglucose and Methylglucose Uptake in Brain of Four Stroke Patients. With Special Reference to the Regional Estimation of the Lumped Constant
Authors: Gjedde Albert , Wienhard Klaus , Heiss Wolf-Dieter , Kloster Gerd , Diemer Nils Henrik , Herholz Karl , Pawlik Günter
Published: April 2011

The glucose metabolic rate of the human brain can be measured with labeled deoxyglucose, using positron emission tomography, provided certain conditions are fulfilled. The original method assumed irreversible trapping of deoxyglucose metabolites in brain during the experimental period, and it further requires that a conversion factor between deoxyglucose and glucose, the “lumped constant,” be known for the brain regions of interest. We examined the assumption of irreversible trapping of fluorodeoxyglucose metabolites in brain of four patients in 365 normal and 4 recently infarcted regions. The average net, steady-state rate of fluorodeoxyglucose ( KD) accumulation in normal regions of the four patients was 0.025 ml g−1 min−1. We also examined the variability of the lumped constant. We first confirmed that methylglucose is not phosphorylated in the human brain. We then estimated the lumped constant from the regional distribution of labeled methylglucose in brain. The average (virtual) volume of distribution of labeled methylglucose in the normal regions was 0.46 ml g−1 and was the same in both gray and white matter structures. The average brain glucose content corresponding to this value was 1.3 μmol g−1, assuming a Michaelis constant ( Kt) of 3.7 m M for glucose transport across the blood–brain barrier. The lumped constant varied insignificantly between 0.4 and 0.5 in most regions, with an overall average of 0.44. It did not vary significantly between the patients and was the same in gray and white matter structures, but was inversely related to the calculated metabolic rate. This observation indicates that metabolic rates calculated with a fixed lumped constant (e.g., 0.40) would be slightly underestimated at high metabolic rates and slightly overestimated at low metabolic rates. The average glucose metabolic rates of the 365 normal regions, in which gray matter regions prevailed by 20:1, was 32 μmol 100 g−1 min−1. The average glucose phosphorylation rate in white matter was 20 μmol 100 g−1 min−1 with a lumped constant of 0.45. In the recently infarcted areas, the lumped constants varied from 0.37 to 2.83, corresponding to glucose metabolic rates varying from 2 to 18 μmol 100 g−1 min−1. Two infarct types were identified. In one type, the phosphorylation-limited type, glucose content and the lumped constant were close to normal (1 μmol g−1 and 0.40, respectively). In the other, the transport/flow-limited type, the glucose content was low (0.2 μmol g−1), and the lumped constant in excess of unity. The evidence from the present study upholds the model of Sokoloff et al. in every detail.
Regional Flow-Metabolism Couple following Middle Cerebral Artery Occlusion in Cats
Authors: Tanaka Kortaro , Greenberg Joel H. , Gonatas Nicholas K. , Reivich Martin
Published: April 2011

The regional flow-metabolism couple was studied during the recovery period after 1 h of left middle cerebral artery (MCA) occlusion in cats. Local CBF (LCBF) was assessed at the end of ischemia as well as at the end of 4 h of recirculation by the microsphere technique. Local CMRgl (LCMRgl) was measured at the end of the recirculation period with [14C]2-deoxyglucose. Histology was evaluated by light microscopy from coronal brain blocks adjacent to those used for the determination of LCBF and LCMRgl. When LCBF in the central and peripheral MCA territories during the recovery period was between 40 and 115% of the value in sham occlusion studies, LCMRgl was greater than the control level found in the sham studies, and was accompanied by slight histological damage. This finding suggests that anaerobic glycolysis may persist after transient ischemia in spite of the recovery of LCBF to a level that is normally greater than the threshold for the activation of anaerobic glycolysis (<40% of the control). Persistent anaerobic glycolysis in the reperfusion period following an ischemic insult may be a sign of early tissue damage. Some of the regions in the peripheral MCA territory with LCBF between 40 and 110% of the levels during the recovery period in the sham studies showed a mild to moderate depression in LCMRgl so that the flow-metabolism ratio remained normal. These regions did not exhibit histological damage. This possible protective mechanism of the tissue in response to ischemia is discussed from the standpoint of the relationship between flow and metabolism.
Correlations between Proton Nuclear Magnetic Resonance Imaging and Retrospective Histochemical Images in Experimental Cerebral Infarction
Authors: Kato Hiroyuki , Kogure Kyuya , Ohtomo Hitoshi , Tobita Muneshige , Matsui Shigeru , Yamamoto Etsuji , Kohno Hideki
Published: April 2011

Evaluation of ischemic brain injury in experimental cerebral infarction in gerbils and rats was performed by means of both proton nuclear magnetic resonance imaging ([1H]NMR-CT) and various histochemical analyses. In vivo nuclear magnetic resonance (NMR) imaging was carried out employing saturation recovery, inversion recovery, and spin echo pulse sequences. Spatial resolution of the images was excellent. The ischemic lesions were detected with a remarkable contrast in inversion recovery and spin echo images within a few hours after insult. Those changes in NMR images consistently corresponded with the various retrospective histochemical observations, especially with methods related to brain edema (K+ staining) rather than structural (enzymatic) studies. Calculated T1 and T2 relaxation times indicated the evolution of the edema state in the brain in situ. They correlated excellently with the retrospective water content measurement. As a result, detailed characterization of the edema state induced by cerebral ischemia was possible in vivo using [1H]NMR imaging.
Pial Artery Responses to Norepinephrine Potentiated by Endothelium Removal
Authors: Sercombe R. , Verrecchia C. , Oudart N. , Dimitriadou V. , Seylaz J.
Published: April 2011

The effect of endothelium removal on pial artery constriction in response to norepinephrine (NE) was studied in vitro using a perfused vessel setup in which pressure increases indicate vasoconstriction. In deendothelialized rabbit arteries, the reaction to extraluminal NE was found to be characterized by a much higher Emax (2.0 times) and a slight (but significant) leftward shift of the concentration-response curve (lower EC50) compared with control vessels. In cat arteries subjected to either extra- or intraluminal NE, the Emax was also substantially higher in deendothelialized preparations (4.4 and 5.1 times, respectively), but there was no significant difference in the EC50 values. Anatomical verification and functional tests (acetylcholine-induced dilatation) confirmed the presence and the absence of the endothelium in control and lesioned arteries, respectively. This modulatory influence of the endothelium may be of importance in cerebrovascular pathology.
Evidence for the Presence of Cholinergic Nerves in Cerebral Arteries: An Immunohistochemical Demonstration of Choline Acetyltransferase
Authors: Saito Akira , Wu Jang-Yen , Lee Tony J.-F.
Published: April 2011

The presence of cholinergic nerves in cerebral arteries of several species was investigated by an immunohistochemical method using antibodies against choline acetyltransferase (ChAT). In cats, pigs, rats, and dogs, ChAT immunoreactivities were found to be associated with large bundles and single fibers in the circle of Willis and anterior cerebral, middle cerebral, and basilar arteries. In the rabbit, the ChAT-immunoreactive (ChAT-I) nerves were also observed in the circle of Willis and anterior and middle cerebral arteries, but only few or none were found in the basilar and vertebral arteries. The ChAT-I nerves were found only in the adventitial layer of vessels examined. Superior cervical ganglionectomy did not appreciably affect the distribution of ChAT-I nerves. These results indicate the presence of cholinergic nerves in cerebral arteries. The distribution pattern of ChAT-I nerves was different from that of vasoactive intestinal polypeptide (VIP)-like-immunoreactive nerves and acetylcholinesterase-positive nerves. The possible coexistence of ChAT and VIP-like substance in the same neuron is discussed.
Blood—Brain Barrier and Peptides
Authors: Ermisch A. , Rühle H.-J. , Landgraf R. , Hess J.
Published: April 2011

The brain is both the source and the recipient of peptide signals. The question is: Do endogenous, blood-borne peptide molecules influence brain function? Brain regions with the tight capillaries of the blood–brain barrier (BBB) extract low but measurable amounts of labeled peptide molecules from an intracarotid bolus injection. In the rat, the extraction fractions of β-casomorphin-5, DesGlyNH2-arginine-vasopressin, arginine-vasopressin, lysine-vasopressin, oxytocin, gonadoliberin, substance P, and β-endorphin, studied in this laboratory, range from 0.5% (substance P) to 2.4% (arginine-vasopressin). Extraction varies little among the 15 examined brain regions. As shown for arginine-vasopressin, the extracted peptides may be bound in part to specific binding sites located on the luminal membrane of the tight endothelial cells. Transport of peptide molecules across the BBB cannot be ruled out, but it is unlikely that endogenous peptides pass the BBB in physiologically significant amounts. In contrast, in brain regions with leaky capillaries, e.g., selected circumventricular organs including the pineal gland, neurohypophysis, and choroid plexus, the peptide fraction extracted approaches that of water. Within the circumventricular organs, the peptide molecules actually reach the cellular elements of the tissue. However, no studies definitively show that peptides reach neurons in the deeper layers of the brain. On the other hand, blood-borne peptides influence the BBB permeability by altering the transport of essential substances. The effect may be mediated by specific peptide binding sites located at the luminal membrane of the endothelium. It is possible that the effect of peptides on the BBB is necessary for proper brain function. There is some evidence that peptides, released centrally into the synaptic clefts as well as peripherally into the bloodstream, support complex brain performances by both of these pathways.
In vivo Measurement of Regional Brain and Tumor pH Using [14C]Dimethyloxazolidinedione and Quantitative Autoradiography
Authors: Arnold James B. , Junck Larry , Rottenberg David A.
Published: April 2011

Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pH, or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume ( Ve) was estimated with [14C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94–7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63–6.90. Thus, the RG-2 glioma is not more “acidic” than adjacent brain tissue and its “alkaline” pHt probably reflects a large extracellular water content and plasma-like extracellular pH.
Cerebral Atrophy and Hypoperfusion Improve during Treatment of Wernicke-Korsakoff Syndrome
Authors: Meyer John Stirling , Tanahashi Norio , Ishikawa Yoshiki , Hata Takashi , Velez Maria , Fann William E. , Kandula Prasab , Mortel Karl F. , Rogers Robert L.
Published: April 2011

Nineteen patients with sudden onset of impaired recent memory, cerebellar ataxia, peripheral neuropathy, and other signs of Wernicke-Korsakoff syndrome (WKS) were treated and examined prospectively for 3 months. Serial studies included histories, neurological examinations, cognitive capacity screening examinations (CCSE), computed tomography (CT) scans, and measurements of regional CBF. Patients were detoxified and withdrawn from sedatives before CBF measurements were examined. Treatment included alcohol withdrawal, nutritious diet, and 300 mg thiamine daily. Before treatment CCSE scores and blood flow values of both white and gray matter were reduced, particularly within both temporoparietal regions. After treatment of compliant patients (n = 10), white and gray matter blood flow increased concurrently with improved CCSE scores. Abnormal eye signs, ataxia, peripheral neuropathy, and performance of activities of daily living also improved. Cerebral atrophy and ventricular enlargement measured by CT decreased. Early recognition and treatment of WKS in compliant patients permit rapid reversals of cognitive and neurological impairments associated with increased blood flow of gray and white matter and improvements of brain atrophy measured by CT scanning.
Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males
Authors: Nehlig Astrid , Porrino Linda J. , Crane Alison M. , Sokoloff Louis
Published: April 2011

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.
Ischemic Brain Damage in Rats following Cardiac Arrest Using a Long-Term Recovery Model
Authors: Blomqvist Photjanee , Wieloch Tadeusz
Published: April 2011

A model is described in which transient complete cerebral ischemia is induced in rats by intracardiac injection of potassium chloride. The animals were intubated and mechanically ventilated with a nitrous oxide/oxygen (70:30) mixture. Cardiac arrest was achieved following a brief period of ventricular fibrillation. After 5–6 min, the circulation was restored by cardiopulmonary resuscitation and partial exchange transfusion. Local CBF (LCBF) during ischemia and cardiac resuscitation was studied by injection of [14C]iodoantipyrine into the right auricle at various periods during cardiac arrest, and was subsequently analyzed by autoradiography. No radioactive tracer could be visualized in any brain structure, demonstrating the absence of CBF during the cardiac standstill. LCBF was also studied at 5 min and 6.5 h after cardiac resuscitation. Five minutes of recirculation showed an increase in blood flow in all brain structures studied, ranging between 130 and 400% of control values. After 6.5 h of recirculation, the CBF was decreased in 13 of 24 brain structures by 20–50%, concomitantly with the depressed rate of glucose utilization found in 15 brain structures. The neocortical, hippocampal, and striatal concentrations of labile phosphates, lactate, pyruvate, phosphocreatine, glucose, and glycogen were measured 5 min after cardiac arrest. Extensive energy failure and elevation of lactate levels were observed and were similar to earlier reported values. One week following recovery from the ischemic insult, the animals were perfusion-fixed with formaldehyde. The brains were embedded in paraffin, sub serially sectioned, and stained with cresyl violet/acid fuchsin. Histopathological changes were assessed by light microscopy as the number of acidophilic or pyknotic neurons. Morphological changes were observed in the hilus of the dentate gyrus, the hippocampal CA1 and subicular regions, the dorsal and lateral septum, the olfactory tubercle, the primary olfactory cortex, the entorhinal cortex, the amygdaloid nuclei, and the reticular nucleus of the thalamus. The distribution of the morphological changes suggests a transsynaptic mechanism, causing neuronal necrosis primarily in the limbic brain areas.
α-Adrenoreceptors and Muscarine Receptors in Human Pial Arteries and Micro Vessels: A Receptor Binding Study
Authors: Ferrari-DiLeo Gabryleda , Potter Lincoln T.
Published: April 2011

Human pial arteries and intraparenchymal microvessels were isolated for enzyme assays and radio-ligand binding studies of receptors. Special attention was paid to contamination with brain tissue, which was assessed by luxol staining and cerebroside assays for myelin and by scanning electron microscopy. The amount of contamination was ∼1% for pial vessels and 14% for microvessel preparations. Significant levels of α1-adrenoreceptors (binding sites for [3H]prazosin) and α2-adrenoreceptors (sites labeled by [3H]azidoclonidine) were found in both types of vessels, suggesting that each receptor can modify contractility in these human vessels. Levels of muscarine receptors (sites labeled with [3H]quinuclidinyl benzilate) and choline acetyltransferase activity were considered significant only in pial vessels.
Reversal of Neurological Deficits by Levallorphan in Patients with Acute Ischemic Stroke
Authors: Handa Nobuo , Matsumoto Masayasu , Nakamura Masaichi , Yoneda Shotaro , Kimura Kazufumi , Sugitani Yoshinori , Tanaka Kenji , Takano Takashi , Kamada Takenobu
Published: April 2011

This study was conducted to examine the effect of the intramuscular injection of levallorphan tartrate (1.0 mg), a mixed agonist-antagonist opiate, on the neurological signs, symptoms, and vital signs in 19 patients with acute ischemic stroke. A temporary improvement of hemiplegia or hemiparesis was observed within several minutes after levallorphan injection in 13 of the patients. There were no significant alterations in blood pressure or pulse rate after injection. The findings indicate that levallorphan may have a temporary improving effect on neurological deficits in acute ischemic stroke. In addition, observation of the response to levallorphan may serve to predict the prognosis of the final neurological outcome in this type of patient.
Serotonin Depression of Local Cerebral Glucose Utilisation after Monoamine Oxidase Inhibition
Authors: Grome John J. , Harper A. Murray
Published: April 2011

The major catabolic enzyme for serotonin, monoamine oxidase (MAO), is present in the endothelium of cerebral vessels. We report the effects of the intracarotid administration of serotonin on local cerebral glucose utilisation in rats following MAO inhibition with the drug clorgyline. It was found that saline, clorgyline, or serotonin alone produced no significant changes in glucose utilisation. Following the infusion of clorgyline, the administration of serotonin produced significant decreases in glucose utilisation in cortical areas of between 12 and 33% and in the caudate nucleus of 16%.
Low-Cost Microcomputer-Based Densitometer
Authors: Richards H. K. , Lovick A. H. J. , Pickard J. D.
Published: April 2011

We have constructed low-cost equipment for the measurement of the optical density of x-ray films. This equipment is based on a video system connected via an analog to digital converter to an Apple microcomputer. The optical density of an x-ray film can thus be accessed by commands in BASIC or machine-code programs. By using a calibrated step-wedge film, we have found a stable linear response for optical densities of up to 0.8.
Regional Alterations in Glucose Consumption and Metabolite Levels during Postischemic Recovery in Cat Brain
Authors: Tanaka K. , Welsh F. A. , Greenberg J. H. , O'Flynn R. , Harris V. A. , Reivich M.
Published: April 2011

Local CMRgl (LCMRgl) and metabolite levels were measured in the same tissue samples following 4 h of recirculation after 1 h of occlusion of the middle cerebral artery in the cat. The rate of glucose utilization was calculated using direct measurement of tissue deoxyglucose-6-phosphate and using a “lumped” constant corrected in each sample for alterations in tissue glucose. Increased LCMRgl (compared with that in sham-operated animals) occurred in regions with only minor alterations in levels of lactate and phosphocreatine. By contrast, LCMRgl was markedly depressed in regions with major changes in lactate and high-energy phosphates. Interestingly, tissue levels of glucose and unphosphorylated deoxyglucose were abnormally elevated in regions with profound energy failure. These results indicate an inhibition of glucose utilization in regions damaged by ischemia, despite the persistent elevation of tissue lactate. Increased glucose metabolism at 4 h post ischemia was detected only in areas with minor anaerobic alteration of metabolite levels.
Effect of Nimodipine on Cerebral Metabolism during Ischemia and Recirculation in the Mongolian Gerbil
Authors: Heffez Dan S. , Passonneau Janet V.
Published: April 2011

The effect of nimodipine on cerebral metabolism during ischemia and reflow was studied in female mongolian gerbils. Animals were divided into three experimental groups. Group 1 received 1 mg/kg nimodipine i.p. 1 h prior to ischemia. Group 2 received an injection of the vehicle, 5% polyethylene glycol 400. Group 3 received an equal volume of normal saline. Cerebral ischemia was induced by bilateral common carotid artery occlusion for 1, 2, or 5 min. Recirculation was established for 0, 1, or 5 min. Sham-operated animals served as non-ischemic controls. Gerbils were killed by microwave irradiation. Regional levels of ATP, phosphocreatine, glucose, glycogen, cyclic AMP, and cyclic GMP were measured in brain extracts using standard assay techniques. Levels of metabolites in sham-operated animals did not differ among Groups 1, 2, and 3. At 1 min of ischemia, cortical and striatal ATP levels were highest in Group 1 (p < 0.05 and p < 0.01, respectively). After 5 min of recirculation, cortical and striatal glucose levels were highest in Group 1 (p < 0.005). Regional levels of the metabolites measured at other times did not differ significantly among the three groups. Pretreatment with nimodipine thus retards the fall in ATP and facilitates the recovery of glucose in mongolian gerbils subjected to common carotid artery occlusion. A regional variability of this effect was observed.
Carotid Artery Injection Technique: Bounds for Bolus Mixing by Plasma and by Brain
Authors: Pardridge William M. , Landaw Elliot M. , Miller Leonard P. , Braun Leon D. , Oldendorf William H.
Published: April 2011

Estimation of Michaelis-Menten kinetic parameters ( Km, Vmax) of blood–brain barrier (BBB) transport processes with the carotid artery single injection technique assumes that mixing of the bolus with unlabeled substrate either from (a) circulating plasma or (b) amino acid efflux from brain, is minimal. The maximum extent to which the bolus could mix by these two sources is quantified in the present studies by measuring 14C-phenylalanine extraction in pentobarbital-anesthetized and conscious rats after the addition of 0–80% rat serum to the arterial injection solution. An upper bound (±SE) of bolus mixing due to mixing from both sources, expressed in terms of percentage of rat plasma, is 8.8 ± 1.9 and 7.0 ± 2.1% for the anesthetized and conscious rat, respectively. The estimated contribution to bolus mixing due to amino acid efflux from brain is 3.3 and 2.1% for the anesthetized and conscious rat, respectively. Based on these estimates, the upper bound for bolus mixing with circulating rat plasma is only 5.5 and 4.9%, respectively, for the anesthetized and conscious catheterized rat. Thus, any bolus mixing after rapid carotid injection is relatively small and is comparable to the mixing effects observed with the carotid artery infusion technique. Mixing effects on the order of 5% are shown to have no significant effect on the estimation of kinetic parameters of BBB nutrient transport, except for neutral and basic amino acid transport, which are characterized by very low Km values relative to the usual amino acid plasma concentrations. In the rat, a 5% mixing results in an enrichment of the bolus concentration of unlabeled amino acid that approximates the Km of the transport process, and this results in an overestimation of the absolute Km value. However, mixing effects are shown to have little, if any, impact on the estimation of the transport Vmax, KD, or apparent Km. Thus, amino acid influx rates predicted from kinetic constants obtained with the carotid injection technique are reliable, even if bolus mixing effects with the carotid injection technique are as high as 7–9%.
Analysis of Some Errors in the Measurement of Oxygen Extraction and Oxygen Consumption by the Equilibrium Inhalation Method
Authors: Correia John A. , Alpert Nathaniel M. , Buxton Richard B. , Ackerman Robert H.
Published: April 2011

Some sources of error in the equilibrium inhalation method for the measurement of oxygen extraction fraction and CMRO2 by positron emission computed tomography scanning have been evaluated by computer simulation. Emphasis has been placed on errors that have not been thoroughly studied in past work. These include effects of random statistical errors, systematic errors in arterial blood radioactivity concentrations, and errors due to perturbations of the equilibrium state, to tissue inhomogeneity, and to subject motion.
Cortical Tissue Pressure Gradients in Early Ischemic Brain Edema
Authors: Hatashita Shizuo , Hoff Julian T.
Published: April 2011

We examined the role of ischemic brain edema, tissue pressure gradients, and regional CBF (rCBF) in adjacent regions of cerebral cortex in cats with middle cerebral artery (MCA) occlusion (MCAO). Tissue pressure, rCBF, and water content were measured from gray matter in the central core and the peripheral margin of the MCA territory over 6 h after MCAO. Ventricular fluid pressure and CSF pressure were recorded. Tissue pressure in the ischemic core, with a flow of ∼5 ml/100 g/min, increased more than that in the periphery where flow was ∼19 ml/100 g/min. Tissue pressure rose progressively to 14.8 ± 1.0 mm Hg in the core over 6 h after MCAO, establishing a significant pressure gradient between that tissue and the lateral ventricle nearby or the subarachnoid space in the middle fossa within the first 3 h. The increase in tissue pressure was linearly related to the amount of edema fluid that developed until the edema reached a severe degree. This study shows that a hydrostatic tissue pressure gradient within ischemic cortex is associated with ischemic brain edema. The magnitude of the gradient that develops is related to the severity of ischemic edema in that tissue.
Effects of a Stable Enkephalin Analogue, (D-Met2,Pro5)-Enkephalinamide, and Naloxone on Cortical Blood Flow and Cerebral Blood Volume in Experimental Brain Ischemia in Anesthetized Cats
Authors: Sándor Péter , Gotoh Fumio , Tomita Minoru , Tanahashi Norio , Gogolak Ivan
Published: April 2011

The effects of intracarotid injection of the stable enkephalin analogue (d-Met2,Pro5)-enkephalinamide (ENK) and intravenous administration of naloxone on the cerebrocortical blood flow (dye dilution method) and cerebral blood volume (CBV) (photoelectric method) were investigated during unilateral brain ischemia in anesthetized cats. Both parameters were measured simultaneously in the intact and ischemic (middle cerebral artery occluded) hemispheres. An intracarotid injection of ENK 0.5 mg/kg induced a significant increase in cortical vascular resistance and a −87% decrease in cerebrocortical blood flow from 25 ± 3 to 4 ± 3 ml/100 g/min, without CBV alteration in the ischemic hemisphere. Naloxone (1 mg/kg i.v.), on the other hand, induced a marked two-fold increase in cerebrocortical blood flow and a significant elevation of CBV from 5.9 ± 0.5 to 7.4 ± 0.7 vol% in the ischemic hemisphere. No change in cerebrocortical blood flow or CBV was observed in the intact hemisphere either after ENK or after naloxone administration. Arterial blood gases and hematocrit remained unchanged. On the basis of the present findings, we conclude that (a) besides other factors, endogenous opioid mechanisms may also participate in ischemic cerebrovascular reactions and (b) the cerebral circulatory effects of naloxone probably reflect its opiate receptor blocking property and not simply its other non–opiate-related actions.
Abstinence Improves Cerebral Perfusion and Brain Volume in Alcoholic Neurotoxicity without Wernicke-Korsakoff Syndrome
Authors: Ishikawa Yoshiki , Meyer John Stirling , Tanahashi Norio , Hata Takashi , Velez Maria , Fann William E. , Kandula Prasab , Motel Karl F. , Rogers Robert L.
Published: April 2011

Twenty severe chronic alcoholic patients with signs of neurotoxicity but without Wernicke-Korsakoff syndrome were treated by abstinence from alcohol and examined prospectively at intervals thereafter. Serial examinations included detailed medical histories, neurological examinations, cognitive capacity screening examinations, computed tomography scans with measurements of sulcal and ventricular volume, and measurements of regional CBF. All sedatives were withdrawn before CBF measurements were made. Before treatment, gray matter blood flow values were significantly reduced compared with those of age-matched normal volunteers, but white matter blood flow values were normal and the ventricles were enlarged. After abstinence from alcohol, mean gray matter blood flow values and brain volume both increased significantly.
High-Performance Digital Image Analyzer for Quantitative Autoradiography
Authors: Lear James L. , Mido Kenneth , Plotnick Jeffrey , Muth Russell
Published: April 2011

A digital image-processing system was developed for high–spatial resolution analysis of autoradiograms. The system uses a linear array of charge-coupled devices operating under computer control to scan and digitize autoradiograms into 512 × 512 matrices with 256 gray levels. Software was developed to facilitate quantitative analysis of autoradiograms produced in single- and multiple-tracer studies. Because of the high output, linearity, and accuracy of the solid-state detectors, the system was found to digitize autoradiograms significantly more precisely and accurately than previously described video camera- or photomultiplier tube-based scanning densitometers.
Normal Distribution of Regional Cerebral Blood Flow Measured by Dynamic Single-Photon Emission Tomography
Authors: Devous M. D. , Stokely E. M. , Chehabi H. H. , Bonte F. J.
Published: April 2011

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1–10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 ± 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = −0.33 ml/min/100 g/year; p < 0.05).
Nicardipine Increases Cerebral Blood Flow but Does Not Improve Neurologic Recovery in a Canine Model of Complete Cerebral Ischemia
Authors: Sakabe Takefumi , Nagai Ikuo , Ishikawa Toshizoh , Takeshita Hiroshi , Masuda Tsutomu , Matsumoto Mishiya , Tateishi Akio
Published: April 2011

The effects of the calcium entry blocker nicardipine on CBF, CMRO2, and neurologic outcome following 10 min of complete cerebral ischemia were examined in dogs. In CBF and CMRO2 studies, the CBF in the untreated group (seven dogs) and the nicardipine group (seven dogs; 20 μg kg−1 at 30 min postischemia and a subsequent infusion of 2 μg kg−1 min−1 for 90 min) initially increased to 300–400% and then returned to preischemic values at 30 min postischemia. Thereafter the CBF in the untreated group significantly decreased to 50% of preischemic values for the following 90-min period (hypoperfusion), while the CBF in the nicardipine group did not differ from preischemic values. The CMRO2 in both groups decreased to ∼50–80% of preischemic values after 15 min postischemia and did not differ between the groups throughout the study. In neurologic outcome studies, 18 dogs were divided into three groups (of six dogs each): untreated; saline infusion only, posttreated; nicardipine as in CBF and CMRO2 studies, pretreated; nicardipine 20 μg kg−1 at 2 min preischemia and a subsequent infusion of 2 μg kg−1 min−1 from immediately postischemia to 120 min postischemia. Nicardipine treatment initiated either before or after ischemia failed to improve neurologic outcome at 48 h postischemia. Thus, the increase of postischemic global CBF by nicardipine is not accompanied by neurologic recovery in a canine model of complete cerebral ischemia.
Effect of Preischemia Cyclooxygenase Inhibition by Zomepirac Sodium on Reflow, Cerebral Autoregulation, and EEG Recovery in the Cat after Global Ischemia
Authors: Stevens Mark K. , Yaksh Tony L. , Hansen Robert B. , Anderson Robert E.
Published: April 2011

Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF–PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 ± 11 vs. 141–146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 ± 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 ± 9 ml/100 g/min). The CBF–PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow.
Studies on the Relationship between Cerebral Glucose Transport and Phosphorylation Using 2-Deoxyglucose
Authors: Hargreaves Richard J. , Planas Anna M. , Cremer Jill E. , Cunningham Vincent J.
Published: April 2011

Regional rates of blood–brain glucose transfer and phosphorylation have been measured in anaesthetized fasted and conscious fed and fasted rats using a dual-label 2-deoxyglucose technique that exploits differences in the early-time distribution of analogue and native glucose between blood and brain. Regional cerebral blood flow was also measured in comparable groups of rats. Estimates of glucose influx in the anaesthetized group were compared with those calculated from previously published kinetic constants obtained using [14C]d-glucose as tracer. The close agreement of these two sets of results served to validate estimates of influx obtained using the glucose analogue. Comparisons between all three groups showed that regional rates of glucose influx were maintained at levels appropriate to the rate of cerebral glucose phosphorylation. This occurred despite wide variations in plasma glucose concentration. The results indicate that at least two factors are involved in the adaptation of glucose supply to meet metabolic demand. One is related to blood flow, and probably reflects changes in the surface area of the capillary endothelium perfused. The second involves changes in the blood–brain barrier permeability to glucose and could reflect changes in the density of functioning glucose transporters within capillary endothelial cell membranes.
Regional Studies of Blood—Brain Barrier Transport of Glucose and Leucine in Awake and Anesthetized Rats
Authors: LaManna Joseph C. , Harik Sami I.
Published: April 2011

d-Glucose and l-leucine are transported across the blood–brain barrier (BBB) by two separate carrier-mediated facilitated diffusion mechanisms. In the awake rat there are regional differences in blood-to-brain glucose transport among the cerebral cortex, cerebellum, hippocampus, and striatum. To determine whether these are due to variations in the regional density or affinity of the glucose transporter moiety of brain capillaries or are secondary to regional tissue perfusion and capillary arrangement characteristics, we studied (a) regional blood-to-brain transport of l-leucine in awake rats; (b) regional blood-to-brain transport of both glucose and leucine under chloral hydrate anesthesia, a condition associated with altered regional brain blood flow (BF) and metabolism; and (c) regional brain vascular volume, derived from the l-glucose and inulin spaces, in both awake and anesthetized rats. We found the same regional differences in blood-to-brain leucine transport in awake rats as we previously described for d-glucose transport. These regional differences in glucose and leucine transport disappear under chloral hydrate anesthesia, as regional differences in BF are abolished. However, we found regional differences in the brain vascular volumes, which are evident in wakefulness and persist during anesthesia. These results suggest that the regional differences in blood-to-brain transport are due mainly to local tissue perfusion and capillary arrangement characteristics rather than to intrinsic regional differences in the transport systems of the BBB.