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Sample records for cerebral metabolic responses

  1. Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

    Science.gov (United States)

    Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

    2017-02-01

    General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

  2. Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Sluijs, M.C. van der; Oeseburg, B.; Folgering, H.T.M.

    2001-01-01

    The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (5610 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl)

  3. Correlation of methylenetetrahydrofolate reductase polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction

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    Gai-Zhuang Liu

    2017-07-01

    Full Text Available Objective: To study the correlation of methylenetetrahydrofolate reductase (MTHFR polymorphism with Hcy metabolism and inflammatory response in patients with recurrent cerebral infarction. Methods: 40 patients with recurrent cerebral infarction who were treated in Yulin Third Hospital between December 2013 and December 2016 were selected as recurrent group, 58 patients with primary cerebral infarction were selected as primary group, and 60 healthy volunteers were selected as control group. Peripheral blood MTHFR gene C677T polymorphism and serum levels of Hcy metabolism indexes and inflammatory response indicators were determined. Results: CC genotype constituent ratio of recurrent group was significantly lower than that of primary group and control group while CT genotype and TT genotype constituent ratio were significantly higher than those of primary group and control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group and primary group were significantly higher than those in control group while VitB12 and FA levels were significantly lower than those in control group; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in recurrent group were significantly higher than those in primary group while VitB12 and FA levels were significantly lower than those in primary group. Serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CC genotype were significantly lower than those in patients with CT genotype and TT genotype while VitB12 and FA levels were significantly higher than those in patients with CT genotype and TT genotype; serum Hcy, HMGB1, sCD40L, YKL-40, Lp-PLA2 and MMP-9 levels in patients with CT genotype were significantly lower than those in patients with TT genotype while VitB12 and FA levels were significantly higher than those in patients with TT genotype. Conclusion: MTHFR gene C677T polymorphism is closely related to the recurrence of cerebral infarction, and allele C

  4. Purine Metabolism in Acute Cerebral Ischemia

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    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

  5. Effects of Hyperglycemia and Effects of Ketosis on Cerebral Perfusion, Cerebral Water Distribution, and Cerebral Metabolism

    Science.gov (United States)

    Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O’Donnell, Martha

    2012-01-01

    Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury. PMID:22498698

  6. Acute hypoxia increases the cerebral metabolic rate

    DEFF Research Database (Denmark)

    Vestergaard, Mark Bitsch; Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob

    2016-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance...... imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N......-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0...

  7. Cerebral Lactate Metabolism After Traumatic Brain Injury.

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    Patet, Camille; Suys, Tamarah; Carteron, Laurent; Oddo, Mauro

    2016-04-01

    Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.

  8. Cerebral blood flow response to functional activation

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only...

  9. Cerebral energy metabolism during induced mitochondrial dysfunction

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    Nielsen, T H; Bindslev, TT; Pedersen, S M

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...

  10. Sleep Slow-Wave Activity Regulates Cerebral Glycolytic Metabolism

    OpenAIRE

    Wisor, Jonathan P; Rempe, Michael J; Schmidt, Michelle A.; Moore, Michele E.; Clegern, William C.

    2012-01-01

    Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1–4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cor...

  11. Cerebral blood flow and metabolism in adults with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten

    2007-01-01

    The intense intrathecal inflammation observed in acute bacterial meningitis (ABM) is associated with pronounced changes in cerebral blood flow (CBF) and metabolism. In seven substudies, CBF and metabolism were measured in adults with ABM as well as healthy volunteers during various interventions....... The studies provide new information about pathophysiological changes, in particular regarding CBF, cerebral oxidative metabolism, and certain aspects of the inflammatory response during ABM. These findings may be important for supportive treatment of patients with this life-threatening disease....

  12. Cerebral blood flow and metabolism during sleep

    DEFF Research Database (Denmark)

    Madsen, Peter Lund; Vorstrup, S

    1991-01-01

    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness......, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different...... levels of sleep into consideration, show that light sleep (stage II) is characterized by global levels of CBF and CMR only slightly reduced by 3-10% below the level associated with wakefulness, whereas CBF and CMR during deep sleep (stage III-IV) is dramatically reduced by 25-44%. Furthermore, recent...

  13. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    . They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  14. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  15. Cerebral hemodynamics and metabolism in patients with moyamoya disease not demonstrating either cerebral infarct or hemorrhage on MRI

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    Kuwabara, Yasuo; Ichiya, Yuichi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masuda, Kouji; Matsushima, Toshio; Fukui, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1995-12-01

    We evaluated the cerebral hemodynamics and metabolism in moyamoya patients who did not demonstrate either cerebral infarct or hemorrhage on MRI. The subjects consisted of 5 patients with moyamoya disease (4 females and one male, aged from 15 to 40 ears). The CBF, OEF and CMRO{sub 2} of the moyamoya patients did not differ from those of the normal control subjects. The CBV did increase significantly in the cerebral cortices and striatum, but not in the cerebellum. The TT was also significantly prolonged in the frontal and parietal regions. The cerebrovascular CO{sub 2} response was markedly impaired in the frontal, temporal and parietal cortices. However, it was relatively preserved in the occipital cortex, thalamus and cerebellum. Thus, the cerebral hemodynamic reserve capacity decreased even in the moyamoya patients not demonstrating either cerebral infarct or hemorrhage on MRI, and it should be considered in the management of these patients. (author).

  16. Effect of Hyperosmolar Solutions on Cerebral Oxygenation and Metabolism

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    S. S. Petrikov

    2008-01-01

    Full Text Available Objective: to assess the time course of changes in the parameters of cerebral oxygenation and metabolism in the correction of intracranial hypertension with hyperosmolar solutions. Material and methods. 39 episodes of elevated intracranial pressure correction with 15% mannitol solution and HyperHAES solution were analyzed in 9 patients with intracranial hemorrhages. Changes in intracranial pressure and systemic hemodynamic, cerebral oxygenation, and metabolic parameters were studied. Results: A great difference was found in the effects of the test solutions on intracranial, cerebral perfusion pressure, and cerebral metabolism. Administration of 15% mannitol solution caused no cerebral metabolic changes. Infusion of HyperHAES solution induced a significant elevation in the concentrations of glucose and pyruvate in the interstitial fluid of both the arbitrarily intact and afflicted cerebral matter. Conclusion: The administration of 15% mannitol solution and HyperHAES solution is an effective method for correcting intracranial hypertension; however, the use of HyperHAES solution results in a more prolonged decrease in intracranial pressure, an increase in cerebral perfusion pressure, and an improvement of cerebral metabolism. Brain lesion due to intracranial hemorrhage may be accompanied by the development of mitochondrial dysfunction. Key words: intracranial hypertension, intracranial pressure, hyperosmolar solutions, tissue microdialysis.

  17. Sleep slow-wave activity regulates cerebral glycolytic metabolism.

    Science.gov (United States)

    Wisor, Jonathan P; Rempe, Michael J; Schmidt, Michelle A; Moore, Michele E; Clegern, William C

    2013-08-01

    Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.

  18. Cerebral vascular control and metabolism in heat stress

    DEFF Research Database (Denmark)

    Bain, Anthony R; Nybo, Lars; Ainslie, Philip N

    2015-01-01

    temperature, and potentiates a condition whereby cerebral oxygenation may be compromised. With levels of experimentally viable passive hyperthermia (up to 39.5-40.0°C core temperature), the associated reduction in CBF (∼30%) and increase in cerebral metabolic demand (∼10%) is likely compensated by increases...

  19. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

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    Seifert, Thomas; Secher, Niels H

    2011-01-01

    This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF......-oxidative carbohydrate uptake during exercise. Adrenaline appears to accelerate cerebral glycolysis through a beta2-adrenergic receptor mechanism since noradrenaline is without such an effect. In addition, the exercise-induced cerebral non-oxidative carbohydrate uptake is blocked by combined beta 1/2-adrenergic blockade......, but not by beta1-adrenergic blockade. Furthermore, endurance training appears to lower the cerebral non-oxidative carbohydrate uptake and preserve cerebral oxygenation during submaximal exercise. This is possibly related to an attenuated catecholamine response. Finally, exercise promotes brain health as evidenced...

  20. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    OpenAIRE

    Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Ku, Ja Gyung; Lee, Hong Seok; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Lee, Jung Sub

    2008-01-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with ...

  1. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard...... polysomnography. Unlike our previous study in man showing a highly significant 25% decrease in CMRO2 during deep sleep (stage 3-4) we found a modest but statistically significant decrease of 5% in CMRO2 during stage 2 sleep. Deep and light sleep are both characterized by an almost complete lack of mental activity....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  2. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    and metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take......The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... this into account, and subsequent methods for measurement of regional glucose metabolism must be corrected accordingly in order to allow reliable quantitative comparisons of metabolite changes in activation studies. For studies of regional metabolic changes during activation quantification poses further...

  3. Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Rasmussen, Peter; Seifert, Thomas

    2011-01-01

    Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium ...

  4. Regulation of cerebral metabolism during cortical spreading depression.

    Science.gov (United States)

    Feuerstein, Delphine; Backes, Heiko; Gramer, Markus; Takagaki, Masatoshi; Gabel, Paula; Kumagai, Tetsuya; Graf, Rudolf

    2016-11-01

    We analyzed the metabolic response to cortical spreading depression that drastically increases local energy demand to restore ion homeostasis. During single and multiple cortical spreading depressions in the rat cortex, we simultaneously monitored extracellular levels of glucose and lactate using rapid sampling microdialysis and glucose influx using 18 F-fluorodeoxyglucose positron emission tomography while tracking cortical spreading depression using laser speckle imaging. Combining the acquired data with steady-state requirements we developed a mass-conserving compartment model including neurons and glia that was consistent with the observed data. In summary, our findings are: (1) Early breakdown of glial glycogen provides a major source of energy during increased energy demand and leaves 80% of blood-borne glucose to neurons. (2) Lactate is used solely by neurons and only if extracellular lactate levels are >80% above normal. (3) Although the ratio of oxygen and glucose consumption transiently reaches levels 90%) of the overall energy supply is from oxidative metabolism. (4) During cortical spreading depression, brain release of lactate exceeds its consumption suggesting that lactate is only a circumstantial energy substrate. Our findings provide a general scenario for the metabolic response to increased cerebral energy demand. © The Author(s) 2015.

  5. Bedside Evaluation of Cerebral Energy Metabolism in Severe Community-Acquired Bacterial Meningitis

    DEFF Research Database (Denmark)

    Rom Poulsen, Frantz; Schulz, Mette; Jacobsen, Anne

    2015-01-01

    BACKGROUND: Mortality and morbidity have remained high in bacterial meningitis. Impairment of cerebral energy metabolism probably contributes to unfavorable outcome. Intracerebral microdialysis is routinely used to monitor cerebral energy metabolism, and recent experimental studies indicate that ...

  6. Cerebral blood flow and oxygen metabolism in the Rett syndrome

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    Yoshikawa, Hideto; Fueki, Noboru; Suzuki, Hisaharu; Sakuragawa, Norio; Iio, Masaaki (National Central Hospital for Mental, Nervous and Muscular Disorders, Tokyo (Japan))

    1992-05-01

    Positron emission tomography (PET) was performed on six patients with the Rett syndrome and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO{sub 2}) was low in five patients, and oxygen extraction fraction (OEF) was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in the Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both the cerebral blood flow (CBF) and CMRO{sub 2} were lower than those for the controls, which may indicate the loss of of hyperfrontality in the Rett syndrome. Distribution of brain metabolism may be immature in the Rett syndrome. (author).

  7. Cerebral hemodynamic and metabolic changes in fulminant hepatic failure

    Directory of Open Access Journals (Sweden)

    Fernando Mendes Paschoal Junior

    Full Text Available ABSTRACT Intracranial hypertension and brain swelling are a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure (FHF. The pathogenesis of these complications has been investigated in man, in experimental models and in isolated cell systems. Currently, the mechanism underlying cerebral edema and intracranial hypertension in the presence of FHF is multi-factorial in etiology and only partially understood. The aim of this paper is to review the pathophysiology of cerebral hemodynamic and metabolism changes in FHF in order to improve understanding of intracranial dynamics complication in FHF.

  8. Local cerebral metabolism during partial seizures

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    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-04-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

  9. Positron emission tomography makes cerebral metabolism visible

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    Meermann, H.

    1982-05-12

    In the present publication the principle and advantage of positron emission topography as a nuclear medical method for the diagnosis of brain diseases are described. By this method the metabolic processes in the brain are measured using labelled compounds which are actively metabolized in the brain. These are for instance glucose, aminoacids and psychopharmaceutics, whose main site of action is in the brain. Thus not only tumorous processes but also regional blood circulation, oxygen absorption, regional protein synthesis, distribution and utilization of carrier substances and the absorption of drugs can be established.

  10. History of International Society for Cerebral Blood Flow and Metabolism.

    Science.gov (United States)

    Paulson, Olaf B; Kanno, Iwao; Reivich, Martin; Sokoloff, Louis

    2012-07-01

    Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research.

  11. Cerebral oxygenation and energy metabolism in bacterial meningitis

    DEFF Research Database (Denmark)

    Larsen, Lykke

    Introduction: In a recent retrospective study of patients with severe bacterial meningitis we demonstrated that cerebral oxidative metabolism was affected in approximately 50% of the cases. An increase of lactate/pyruvate (LP) ratio above the upper normal limit, defined according to according...... bacterial meningitis; secondly to examine whether it is correct to separate the diagnosis of cerebral ischemia from mitochondrial dysfunction based exclusively on the biochemical pattern obtained during intracerebral microdialysis. Method: A prospective clinical study including patients with severe...... community acquired bacterial meningitis admitted to the Department of Infectious Diseases, Odense University Hospital, during the period January 2014 to June 2016. We relate data from measurements of brain tissue oxygen tension (PbtO2) to simultaneously recorded data reflecting cerebral cytoplasmic redox...

  12. [Impact of xenon anesthesia on cerebral oxygenation and metabolism in neurosurgical patients].

    Science.gov (United States)

    Rylova, A V; Lubnin, A Iu

    2011-01-01

    In recent years the background for xenon anesthesia implementation in neurosurgery has been created. A variety of researches have been conducted though very few of them concerned xenon effect upon cerebral metabolism. We assessed cerebral oxygenation and cerebral metabolism during propofol anesthesia followed by xenon closed circuit anesthesia in neurosurgical patients. Xenon inhalation was marked by higher jugular vein saturation, oxygen content and glucose level and lower arterio-venous difference. We conclude that compared to propofol xenon improves cerebral oxygenation and decreases cerebral metabolism in neurosurgical patients.

  13. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

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    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-06-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

  14. Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants.

    Science.gov (United States)

    Lin, Pei-Yi; Roche-Labarbe, Nadege; Dehaes, Mathieu; Carp, Stefan; Fenoglio, Angela; Barbieri, Beniamino; Hagan, Katherine; Grant, P Ellen; Franceschini, Maria Angela

    2013-03-14

    Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain

  15. Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Huber, M.; Herholz, K.; Pawlik, G.; Szelies, B.; Juergens, R.H.; Heiss, W.D.

    1989-01-01

    Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level.

  16. Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude

    DEFF Research Database (Denmark)

    Møller, Kirsten; Paulson, Olaf B; Hornbein, Thomas F.

    2002-01-01

    . Global cerebral blood flow at rest and during exercise on a bicycle ergometer was measured by the Kety-Schmidt technique. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by the Fick principle. Cerebral function was assessed by a computer-based measurement of reaction time...... and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow......The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level...

  17. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  18. Regional specific changes of cerebral metabolism in systemic lupus erythematosus identified by positron emission tomography

    NARCIS (Netherlands)

    de Jong, BM; Pruim, J; Sinnige, LGF; Beintema, KD; Spronk, PE; Bootsma, H; Kallenberg, CGM; van Zomeren, AH; Haaxma-Reiche, H

    1999-01-01

    In order to test the hypothesis whether the pathogenesis of cerebral systemic lupus erythematosus (SLE) may include an immune-mediated deficit in specific vulnerable brain regions, the regional cerebral metabolism in 9 patients with diffuse as well as focal cerebral symptoms was compared with that

  19. Lipid Metabolism, Abdominal Adiposity, and Cerebral Health in the Amish.

    Science.gov (United States)

    Ryan, Meghann; Kochunov, Peter; Rowland, Laura M; Mitchell, Braxton D; Wijtenburg, S Andrea; Fieremans, Els; Veraart, Jelle; Novikov, Dmitry S; Du, Xiaoming; Adhikari, Bhim; Fisseha, Feven; Bruce, Heather; Chiappelli, Joshua; Sampath, Hemalatha; Ament, Seth; O'Connell, Jeffrey; Shuldiner, Alan R; Hong, L Elliot

    2017-11-01

    To assess the association between peripheral lipid/fat profiles and cerebral gray matter (GM) and white matter (WM) in healthy Old Order Amish (OOA). Blood lipids, abdominal adiposity, liver lipid contents, and cerebral microstructure were assessed in OOA (N = 64, 31 males/33 females, ages 18-77). Orthogonal factors were extracted from lipid and imaging adiposity measures. GM assessment used the Human Connectome Project protocol to measure whole-brain average cortical thickness. Diffusion-weighted imaging was used to derive WM fractional anisotropy and kurtosis anisotropy measurements. Lipid/fat measures were captured by three orthogonal factors explaining 80% of the variance. Factor one loaded on cholesterol and/or low-density lipoprotein cholesterol measurements; factor two loaded on triglyceride/liver measurements; and factor three loaded on abdominal fat measurements. A two-stage regression including age/sex (first stage) and the three factors (second stage) examined the peripheral lipid/fat effects. Factors two and three significantly contributed to WM measures after Bonferroni corrections (P < 0.007). No factor significantly contributed to GM. Blood pressure (BP) inclusion did not meaningfully alter the lipid/fat-WM relationship. Peripheral lipid/fat indicators were significantly and negatively associated with cerebral WM rather than with GM, independent of age and BP level. Dissecting the fat/lipid components contributing to different brain imaging parameters may open a new understanding of the body-brain connection through lipid metabolism. © 2017 The Obesity Society.

  20. The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans

    DEFF Research Database (Denmark)

    Volianitis, S.; Fabricius-Bjerre, A.; Overgaard, A.

    2008-01-01

    Intense exercise decreases the cerebral metabolic ratio of O(2) to carbohydrates (glucose + (1/2) lactate) and the cerebral lactate uptake depends on its arterial concentration, but whether these variables are influenced by O(2) availability is not known. In six males, maximal ergometer rowing.......05) in the immediate recovery. During exercise, the cerebral metabolic ratio decreased from 5.67 +/- 0.52 at rest to 1.70 +/- 0.23 (P exercise with room air, and it reached 87.6 +/- 1.0% and 98.9 +/- 0.......2% during exercise with an inspired O(2) fraction of 0.17 and 0.30, respectively. Whilst the increase in a-v lactate difference was attenuated by manipulation of cerebral O(2) availability, the cerebral metabolic ratio was not affected significantly. During maximal rowing, the cerebral metabolic ratio...

  1. Cerebral blood flow and metabolism during exercise: implications for fatigue

    DEFF Research Database (Denmark)

    Seifert, T.; Lieshout, J.J. van; Secher, Niels

    2008-01-01

    , and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain...

  2. Cerebral metabolic abnormalities in children with congenital oculomotor apraxia

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Sung June; Kim, Yu Kyoong; Oh, Yeong Mi; Song, Yoo Sung; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Congenital ocular motor apraxia (COMA) is a rare impairment of saccadic eye movement in horizontal direction. The typical symptom is poor vision or compensatory head thrusting movement. In this study, we investigate the brain metabolic changes in children with COMA using FDG PET. Brain FDG PET studies were performed in 6 children (mean age: 5.82.1 years, M: F=5: 1) with typical COMA by clinical diagnosis. For comparison purpose, age-matched healthy subjects (mean age: 6.42.2 years, M: F = 4: 1) were selected among sibling. Measures of significant difference in cerebral metabolism between the patients and control group were determined using statistical parametric mapping (SPM2). Four of six had the structural abnormalities limited in the cerebellar vermis, and the other two had no structural lesion. FDG PET of patients revealed the significant regional hypometabolism in the left inferior parietal lobule (BA 40) and the bilateral occipital cortices as well as cerebellar vermis (P < 0.005, k=100) in comparison with healthy control group. Meanwhile, hypermetabolism was observed in the right precentral gyrus (BA 6), bilateral frontal gyri (BA 8/BA 10). FDG PET could demonstrate the regional metabolic changes in patients with congenital motor apraxia, which may indicate the functional disturbance in the brain regions related with saccadic eye movement and the compensatory hyperfunction in their head motion.

  3. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Wildschiødtz, Gordon

    1991-01-01

    It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions...... on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography...

  4. History of International Society for Cerebral Blood Flow and Metabolism

    DEFF Research Database (Denmark)

    Paulson, Olaf B; Kanno, Iwao; Reivich, Martin

    2012-01-01

    Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings...... since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has...... grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success...

  5. Regional cerebral glucose metabolism during sevoflurane anaesthesia in healthy subjects studied with positron emission tomography

    DEFF Research Database (Denmark)

    Schlünzen, L; Juul, N; Hansen, K V

    2010-01-01

    BACKGROUND: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. METHODS: Eight...... monitored and bispectral index responses were registered. Statistical parametric maps and conventional regions of interest analysis were used to determine rGMR differences. RESULTS: All subjects were unconsciousness at 1.0 MAC sevoflurane. Cardiovascular and respiratory parameters were constant over time...

  6. Changes in cerebral oxidative metabolism in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P N; Larsen, F S

    2013-01-01

    acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine...... concentration, as well as to some of the adenosine triphosphate degradation products. However, clinical observations of cerebral exchange rates of oxygen, glucose, lactate and amino acids challenge the interpretation of these findings. In this review the conflicting data of cerebral metabolism during acute...

  7. Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms

    DEFF Research Database (Denmark)

    Madsen, J B; Cold, G E; Hansen, E S

    1987-01-01

    ). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping......Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification...... of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension....

  8. Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals

    NARCIS (Netherlands)

    Fisher, James P.; Hartwich, Doreen; Seifert, Thomas; Olesen, Niels D.; McNulty, Clare L.; Nielsen, Henning B.; van Lieshout, Johannes J.; Secher, Niels H.

    2013-01-01

    We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% Wmax), high (75% W(max)) and exhaustive (100% W(max)) workloads. Mean middle cerebral artery blood

  9. [Cerebral infarct and the immune response].

    Science.gov (United States)

    Bartko, D; Lesický, O; Buc, M

    1997-06-01

    There are only few data available regarding the immunological mechanisms for cerebral infarction. The aim of this study was to find out the humoral and cell-mediated immunity under the conditions of focal brain ischemia (CI). As a method for humoral immunity, the complement consumption test against a panel of 8 antigens, quantitative analysis of immunoglobins and fractionized sedimentation of erythrocytes were used in the group of pts with CI, and the group of atherosclerotics (AS) and hypertonics (VH), potential victims of focal brain ischemia. It was found that the occurrence of antibodies against the whole panel of antigens in the group of CI is significantly higher as compared with the healthy controls, but it is lower than that in the group of AS and VH. The occurrence of antibodies exclusively against only brain antigens and that in CSF is similar. No correlation to the location of ischemic lesion and the degree of neurological deficit score was found. These findings didn't change in 2 and 4 weeks as well as in 1 year after the onset of CI. The quantitative analysis of immunoglobins revealed statistically higher levels of IgA and lower levels of IgM in comparison with the controls. IgG were higher, but without statistical significance. Statistically significant higher levels of all immunoglobins in CSF were found. As similar trend of changes found also in the group of AS and VH. These results of humoral immunity confirmed by the results of fractionized sedimentation of erythrocytes with EP. The results can be interpreted as a possible change or disorder of central regulation of immunizing processes due to the latent (in AS and VH) of manifest (in CI) lesions of the brain. But the quality and quantity of this response might have been affected by the entire case history of the patients who survived cerebral infarction. The changes in immunity response of the organism in CI was shown also in cell-mediated immunity. The results a statistically significant

  10. SUPPLY AND DEMAND IN CEREBRAL ENERGY METABOLISM: THE ROLE OF NUTRIENT TRANSPORTERS

    OpenAIRE

    Simpson, Ian A.; Carruthers, Anthony; Vannucci, Susan J.

    2007-01-01

    Glucose is the obligate energetic fuel for the mammalian brain and most studies of cerebral energy metabolism assume that the vast majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter proteins (GLUTs) deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose...

  11. Effect of the acquisition enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both

  12. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Knudsen, Karen Birgitte Moos; Kondrup, Jens

    2001-01-01

    BACKGROUND & AIMS: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine...... metabolism. METHODS: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8). Cerebral blood flow was measured by the 133Xe washout technique. Blood samples for determination of ammonia and amino acids were drawn simultaneously from the radial artery...

  13. Global cerebral blood flow and metabolism during acute hyperketonemia in the awake and anesthetized rat

    DEFF Research Database (Denmark)

    Linde, Rasmus; Hasselbalch, Steen G.; Topp, Simon

    2006-01-01

    In the human setting, it has been shown that acute increase in the concentration of ketone bodies by infusion of beta-hydroxybutyrate increased the cerebral blood flow (CBF) without affecting the overall cerebral metabolic activity. The mechanism by which this effect of ketone bodies was mediated...... and during infusion of ketone bodies. During acute hyperketonemia (average concentration of beta-hydroxybutyrate: 6 mmol/L), global CBF increased 65% from 108 to 178 mL/100 g min and the cerebral metabolic rates for both oxygen and glucose remained constant. This resetting of the relation between CBF...

  14. Sympathetic influence on cerebral blood flow and metabolism during exercise in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    as evidenced by pharmacological manipulation of adrenergic and cholinergic receptors. Cholinergic blockade by glycopyrrolate blocks the exercise-induced increase in the transcranial Doppler determined mean flow velocity (MCA Vmean). Conversely, alpha-adrenergic activation increases that expression of cerebral......This review focuses on the possibility that autonomic activity influences cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from cerebral autoregulation, the arterial carbon dioxide tension, and neuronal activation, it may be that the autonomic nervous system influences CBF...... perfusion and reduces the near-infrared determined cerebral oxygenation at rest, but not during exercise associated with an increased cerebral metabolic rate for oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control of CBF. CMRO(2) does not change during even intense handgrip...

  15. Cerebral blood flow and oxygen metabolism in patients with Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Shin; Ujike, Takashi; Kuroki, Soemu; Sakamoto, Shizuki; Soeda, Toshiyuki; Terashi, Akiro; Iio, Masaaki.

    1988-10-01

    The purpose of this study was to determine functional changes in the cerebral cortex and basal ganglia in Parkinson's disease (PD). Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO/sub 2/) were determined using 0-15 positron emission tomography in 10 PD patients and five age-matched healthy volunteers. There was a tendency among PD patients towards a decreased CBF and CMRO/sub 2/ in the cerebral cortex and basal ganglia. These values were significantly lower in the frontal cortex in the PD group than the control group. There was no difference in OEF between the groups. A more decreased cerebral oxygen metabolism was observed in patients staged as severer on the scale of Hoehn and Yahr. There was no correlation between cerebral oxygen metabolism and tremor, rigidity, or bradykinesis. A decreased cerebral oxygen metabolism was associated with mental disorders, such as depression, hallucination, and dementia. These results may provide an important clue for the understanding of mesocortical dopaminergic pathway and the relationship between PD and dementia. (N.K.).

  16. Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

    Science.gov (United States)

    Xu, Lili; Hu, Zhiyong; Shen, Jianjun; McQuillan, Patrick M

    2015-04-01

    Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (pGinkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C Magnetic Resonance Spectroscopic Imaging

    DEFF Research Database (Denmark)

    Butt, Sadia Asghar; Søgaard, Lise Vejby-Christensen; Magnusson, Peter O.

    2012-01-01

    The branched chain amino acid transaminase (BCAT) has an important role in nitrogen shuttling and glutamate metabolism in the brain. The purpose of this study was to describe the cerebral distribution and metabolism of hyperpolarized 2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnetic...

  18. Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks.

    Science.gov (United States)

    Jog, Mayank A; Yan, Lirong; Kilroy, Emily; Krasileva, Kate; Jann, Kay; LeClair, Holly; Elashoff, David; Wang, Danny J J

    2016-07-01

    The neurobiological interpretation of developmental BOLD fMRI findings remains difficult due to the confounding issues of potentially varied baseline of brain function and varied strength of neurovascular coupling across age groups. The central theme of the present research is to study the development of brain function and neuronal activity through in vivo assessments of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) both at baseline and during the performance of a working memory task in a cohort of typically developing children aged 7 to 18years. Using a suite of 4 emerging MRI technologies including MR blood oximetry, phase-contrast MRI, pseudo-continuous arterial spin labeling (pCASL) perfusion MRI and concurrent CBF/BOLD fMRI, we found: 1) At baseline, both global CBF and CMRO2 showed an age related decline while global OEF was stable across the age group; 2) During the working memory task, neither BOLD nor CBF responses showed significant variations with age in the activated fronto-parietal brain regions. Nevertheless, detailed voxel-wise analyses revealed sub-regions within the activated fronto-parietal regions that show significant decline of fractional CMRO2 responses with age. These findings suggest that the brain may become more "energy efficient" with age during development. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals

    DEFF Research Database (Denmark)

    Fisher, James P; Hartwich, Doreen; Seifert, Thomas

    2013-01-01

    We evaluated cerebral perfusion, oxygenation, and metabolism in eleven young (age 22 ± 1 years) and nine older (age 66 ± 2 years) individuals at rest and during cycling exercise at low (25% W(max)), moderate (50% W(max)), high (75% W(ma)) and exhaustive (100% W(max)) workloads. Mean middle cerebral...... artery blood velocity (MCA V(mean)), mean arterial pressure (MAP), cardiac output (CO) and the partial pressure of arterial carbon dioxide (PaCO(2)) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O(2......)), glucose and lactate across the brain. The molar ratio between the cerebral uptake of O(2) versus carbohydrate (O(2)-carbohydrate index; O(2) / [glucose + 0.5 lactate]; OCI), the cerebral metabolic rate of O(2) (CMRO(2)) and changes in mitochondrial O(2) tension (P(mito)O(2)) were calculated. W...

  20. A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis

    OpenAIRE

    Ferguson MJ; Randles ML; de Freitas DG

    2017-01-01

    Martin J Ferguson,1 Maria L Randles,2 Declan G de Freitas3 1Pharmacy Department, Beaumont Hospital, Beaumont, Dublin, 2Pharmacy Department, Wexford General Hospital, Wexford, 3Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.Case summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive...

  1. Effect of drugs used in psychoses on cerebral dopamine metabolism

    Science.gov (United States)

    O'Keeffe, Ruth; Sharman, D. F.; Vogt, Marthe

    1970-01-01

    1. Chlorpromazine 15 mg/kg, given daily to cats for 2 weeks, produced a rise in homovanillic acid (HVA) content of the caudate nucleus, whereas the same dose of thioridazine lacked this effect. Of these two drugs, only chlorpromazine causes a high incidence of drug-induced Parkinsonism in man. 2. In the mouse, chlorpromazine, thioridazine and haloperidol increased striatal concentrations of HVA and accelerated the disappearance of dopamine (DA) after inhibition of catecholamine synthesis with α-methyltyrosine. Low doses of the three compounds increased, whereas high doses reduced, the concentration of DA in the striatum. In their effects on the DA metabolism of the mouse, chlorpromazine and thioridazine had the same potency, but haloperidol was between 10 and 100 times more active than the other two drugs. In producing hypothermia and sedation, the three compounds were equiactive. 3. Oxypertine, another drug apt to produce Parkinsonism in man, caused a severe reduction in striatal DA and hypothalamic noradrenaline (NA). Though the clinical signs produced in the mouse were indistinguishable from those seen after the same dose of chlorpromazine, the biochemical changes in the brain were thus quite different. 4. Though all the drugs used caused temporary motor disabilities in animals, these bore no resemblance to human Parkinsonism, even when treatment was continued for 7 weeks or more as it was in cats and monkeys. The latter were treated with chlorpromazine 7·5 mg/kg daily, a dose chosen to avoid loss of weight and which may have been too small to produce toxic side-effects. It caused no changes in striatal DA turnover. 5. Even at the high dose of 50 mg/kg, phenoxybenzamine did not increase DA turnover in mouse brain, but it sedated the mice as did the tranquillizers. 6. Atropine sulphate, 25 mg/kg, reduced the HVA content of mouse striatum and partially antagonized the rise in HVA produced by phenothiazines. The effect was surmountable. Possible modes of action

  2. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Investigation of cerebral metabolism by positron CT in Japanese following musical stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Wakasugi, Naotoshi (Nihon Univ., Tokyo (Japan). School of Medicine)

    1994-02-01

    Cerebral metabolic responses to Japanese and Western instrumental music were examined using [sup 11]C-glucose and positron CT. Eight right-handed subjects were studied in both Japanese and Western music-stimulated states. Biaural musical stimulation with a Japanese instrument, the 'shakuhachi', produced diffuse metabolic changes in the left temporal lobe in all subjects. Biaural musical stimulation with a Western instrument, the 'violin', produced metabolic changes in the right temporal lobe in 3 subjects, changes in the left in 4, and changes on both sides in one. It was considered previously that all musical stimulation led to hypermetabolism in the right hemisphere of human beings. However, the present results indicated that Japanese music produced activation of the left hemisphere in Japanese. On the other hand, Western music produced right hemispheric hypermetabolism in Japanese with no emotion. The laterality of the hemisphere stimulated by Western music was apparently incidentally changed according to the state of mind the Japanese subjects. (author).

  4. Improved cerebral energetics and ketone body metabolism in db/db mice.

    Science.gov (United States)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D; Waagepetersen, Helle S

    2017-03-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-13C]glucose, [1,2-13C]acetate or [U-13C]β-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-13C]acetate and [U-13C]β-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

  5. A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R

    2003-01-01

    During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differe......During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio......-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy...... young subjects. In a second experiment magnetic resonance spectroscopy ((1)H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AV(O2) from 3.2 +/- 0.1 at rest to 3.5 +/- 0.2 mM (mean +/-s.e.m.; P

  6. Cerebral blood flow and oxidative metabolism during human endotoxemia

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Qvist, Jesper

    2002-01-01

    and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO reactivity), and 90 minutes after an intravenous bolus...

  7. Local cerebral blood flow and glucose metabolism during seizure in spontaneously epileptic El mice

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Chisa; Ochi, Hironobu; Yamagami, Sakae; Kawabe, Joji; Kobashi, Toshiko; Okamura, Terue; Yamada, Ryusaku [Osaka City Univ. (Japan). Faculty of Medicine

    1995-09-01

    Local cerebral blood flow and glucose metabolism were examined in spontaneously epileptic El mice using autoradiography with {sup 125}I-IMP and {sup 14}C-DG in the interictal phase and during seizure. El (+) mice that developed generalized tonic-clonic convulsions and El (-) mice that received no stimulation and had no history of epileptic seizures were examined. The seizure non-susceptible, maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in mouse brain were calculated using the autoradiographic density. In the interictal phase, the pattern of local cerebral blood flow of El (+) mice was similar to that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly matched. During seizure, no significant changed blood flow and increased glucose metabolism in the hippocampus, the epileptic focus, and no markedly changed blood flow and depressed glucose metabolism in other brain regions were observed and considered to be flow-metabolism uncoupling. These observations have never been reported in clinical or experimental studies of epilepsy. Seizures did not cause large regional differences in cerebral blood flow. Therefore, only glucose metabolism is useful for detection of the focus of secondary generalized seizures in El mice, and appeared possibly to be related to the pathophysiology of secondary generalized epilepsy in El mice. (author).

  8. Improved cerebral energetics and ketone body metabolism in db/db mice

    DEFF Research Database (Denmark)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D

    2017-01-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate ...... metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism....... for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]β-hydroxybutyrate and tissue...... extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice...

  9. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1{+-}4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69{+-}0.09 {mu} g/dL), while 14 (mean age, 67.2{+-}4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27{+-}0.03 {mu} g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted.

  10. Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima S; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2016-07-01

    Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS

    DEFF Research Database (Denmark)

    Blinkenberg, M; Jensen, C.V.; Holm, S

    1999-01-01

    OBJECTIVE: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. BACKGROUND: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression...... in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function. METHODS: The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability...... and parietal cortical areas. There was a statistically significant increase of disability (pstudy, but changes in CMRglc were not correlated to changes in TLA and EDSS. CONCLUSIONS: Global cortical cerebral metabolism in MS is decreased significantly during a 2...

  12. Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Møller, Kirsten; Volianitis, Stefanos

    2002-01-01

    ergometer. The gCBF and cerebral metabolic rates of oxygen, glucose, and lactate were determined with the Kety-Schmidt technique after 15 min of exercise when core temperature was similar across trials, and at the end of exercise, either when subjects remained normothermic (core temperature = 37.9 degrees C......The development of hyperthermia during prolonged exercise in humans is associated with various changes in the brain, but it is not known whether the cerebral metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance-trained subjects completed two exercise bouts on a cycle......; control) or when severe hyperthermia had developed (core temperature = 39.5 degrees C; hyperthermia). The gCBF was similar after 15 min in the two trials, and it remained stable throughout control. In contrast, during hyperthermia gCBF decreased by 18% and was therefore lower in hyperthermia compared...

  13. Cerebral oxygen metabolism in patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen

    2011-01-01

    -normalized values. RESULTS: No group differences were detected in regional magnitudes of CMRO(2) or CBF. Upon normalization using the reference cluster method, significant relative CMRO(2) decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical......) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. MATERIALS AND METHODS: Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity...... relative CMRO(2) decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO(2), CBF, and CMRglc...

  14. Studying cerebral hemodynamics and metabolism using simultaneous near-infrared spectroscopy and transcranial Doppler ultrasound: a hyperventilation and caffeine study

    Science.gov (United States)

    Yang, Runze; Brugniaux, Julien; Dhaliwal, Harinder; Beaudin, Andrew E; Eliasziw, Misha; Poulin, Marc J; Dunn, Jeff F

    2015-01-01

    Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on middle cerebral artery peak blood flow velocity (Vp), brain tissue oxygenation (StO2), total hemoglobin (tHb), and cerebral oxygen metabolism (CMRO2) in five subjects. Hyperventilation-induced hypocapnia served as a control to verify the sensitivity of our measurements. During hypocapnia (∼16 mmHg below resting values), Vp decreased by 40.0 ± 2.4% (95% CI, P < 0.001), while StO2 and tHb decreased by 2.9 ± 0.3% and 2.6 ± 0.4%, respectively (P = 0.003 and P = 0.002, respectively). CMRO2, calculated using the Fick equation, was reduced by 29.3 ± 9% compared to the isocapnic-euoxia baseline (P < 0.001). In the pharmacological experiments, there was a significant decrease in Vp, StO2, and tHb after ingestion of 200 mg of caffeine compared with placebo. There was no significant difference in CMRO2 between caffeine and placebo. Both showed a CMRO2 decline compared to baseline showing the importance of a placebo control. In conclusion, this study showed that profound hypocapnia impairs cerebral oxidative metabolism. We provide new insight into the effects of caffeine on cerebral hemodynamics. Moreover, this study showed that multimodal NIRS/TCD is an excellent tool for studying brain hemodynamic responses to pharmacological interventions and physiological challenges. PMID:25907789

  15. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2013-01-01

    Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood amm...

  16. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...

  17. Comparison Between Cerebral Tissue Oxygen Tension and Energy Metabolism in Experimental Subdural Hematoma

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Engell, Susanne I; Johnsen, Rikke Aagaard

    2011-01-01

    BACKGROUND: An experimental swine model (n = 7) simulating an acute subdural hematoma (ASDH) was employed (1) to explore the relation between the brain tissue oxygenation (PbtO(2)) and the regional cerebral energy metabolism as obtained by microdialysis, and (2) to define the lowest level of PbtO...

  18. Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage

    Science.gov (United States)

    Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P. Ellen; Franceschini, Maria Angela

    2016-05-01

    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.

  19. Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

    Science.gov (United States)

    Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

    2017-04-01

    Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Changes in Cardiorespiratory Responses and Kinematics with Hippotherapy in Youth with and without Cerebral Palsy

    Science.gov (United States)

    Rigby, Brandon Rhett; Gloeckner, Adam Robert; Sessums, Suzanne; Lanning, Beth Anne; Grandjean, Peter Walter

    2017-01-01

    Purpose: The purpose of this study was to characterize pelvic displacement and cardiorespiratory responses to simulated horseback riding and walking in youth with cerebral palsy and to compare responses to youth without cerebral palsy before and after 8 weeks of hippotherapy. Method: Eight youth with cerebral palsy (M[subscript age] = 10 ± 4…

  1. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    Energy Technology Data Exchange (ETDEWEB)

    Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

    1989-01-01

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using /sup 18/F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences.

  2. Marked reduction of cerebral oxygen metabolism in patients with advanced cirrhosis; A positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Kawatoko, Toshiharu; Murai, Koichiro; Ibayashi, Setsurou; Tsuji, Hiroshi; Nomiyama, Kensuke; Sadoshima, Seizo; Eujishima, Masatoshi; Kuwabara, Yasuo; Ichiya, Yuichi (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1992-01-01

    Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO{sub 2}), and oxygen extraction fraction (rOEF) were measured using positron emission tomography (PET) in four patients with cirrhosis (two males and two females, aged 57 to 69 years) in comparison with those in five age matched controls with previous transient global amnesia. PET studies were carried out when the patients were fully alert and oriented after the episodes of encephalopathy. In the patients, rCBF tended to be lower, while rCMRO{sub 2} was significantly lowered in almost all hemisphere cortices, more markedly in the frontal cortex. Our results suggest that the brain oxygen metabolism is diffusely impaired in patients with advanced cirrhosis, and the frontal cortex seems to be more susceptible to the systemic metabolic derangements induced by chronic liver disease. (author).

  3. APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

    Directory of Open Access Journals (Sweden)

    Steven Moore

    2015-05-01

    Full Text Available Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD. To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.

  4. Cerebral glucose metabolic differences in patients with panic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M. (NIMH, Bethesda, MD (USA))

    1990-08-01

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer (F-18)-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task.

  5. Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Strauss, Gitte Irene; Thomsen, Gerda

    2002-01-01

    BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates...... and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ...

  6. A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis

    Directory of Open Access Journals (Sweden)

    Ferguson MJ

    2017-09-01

    Full Text Available Martin J Ferguson,1 Maria L Randles,2 Declan G de Freitas3 1Pharmacy Department, Beaumont Hospital, Beaumont, Dublin, 2Pharmacy Department, Wexford General Hospital, Wexford, 3Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.Case summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing. After an initial high level, her dose was reduced, but over the following weeks, she required several dose increases in order to achieve a voriconazole level within the target range. The patient’s dose requirements eventually stabilized at 700 mg twice daily. Cimetidine and omeprazole were added in an effort to inhibit the metabolism of voriconazole.Discussion: The metabolism of voriconazole is known to be highly variable among different patients depending on pharmacogenetic factors; however, an increasing rate of voriconazole metabolism in a single patient over time is not well recognized. Therapeutic drug monitoring of voriconazole in this case facilitated the use of large doses while controlling for toxicity.Conclusion: This case is further evidence of autoinduction in voriconazole metabolism. Therapeutic drug monitoring of voriconazole is useful in detecting variation in a patient’s metabolism of voriconazole over time. Keywords: voriconazole, therapeutic drug monitoring, metabolism, enzyme inhibition, autoinduction 

  7. Determination of patterns of regional cerebral glucose metabolism in normal aging and dementia

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, A.; Chawluk, J.; Hurtig, H.; Dann, R.; Rosen, M.; Kushner, M.; Silver, F.; Reivich, M.

    1985-05-01

    Regional cerebral metabolic rates for glucose (rCMRGlc) were measured using 18F-FDG and positron emission tomography (PET) in 14 patients with probable Alzheimer's disease (AD) (age=64), 9 elderly controls (age=61), and 9 young controls (age=28). PET studies were performed without sensory stimulation or deprivation. Metabolic rates in individual brain regions were determined using an atlas overlay. Relative metabolic rates (rCMRGl c/global CMRGlc) were determined for all subjects. Comparison of young and elderly controls demonstrated significant decreases in frontal metabolism (rho<0.005) and right inferior parietal (IP) metabolism (rho<0.02) with normal aging. Patients with mild-moderate AD (NMAD) (n=8) when compared to age-matched controls, showed further reduction in right IP metabolism (rho<0.02). SAD patients also demonstrated metabolic decrements in left hemisphere language areas (rho<0.01). This latter finding is consistent with language disturbance observed late in the course of the disease. Out data reveal progressive changes in patterns of cerebral glucose utilization with aging and demential with reflect salient clinical features of these processes.

  8. Effect of STA-proximal MCA bypass. Improvement of cerebral blood flow and metabolism and neuropsychological function

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Akira; Funayama, Masayuki; Miura, Kazuyuki; Ogasawara, Kuniaki; Suzuki, Michiyasu; Kuroda, Kiyoshi; Sasaki, Toshiaki [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1998-11-01

    We investigated cerebral blood flow (CBF) and metabolism in patients with hemodynamic ischemia by positron emission tomography (PET) and thermal diffusion flow meter. We also studied neuropsychological functions to evaluate the effects of surgical revascularization. Bypass surgery of the superficial temporal artery to the proximal middle cerebral artery was performed on 26 patients satisfying the following categories: stenosis or occlusive lesion in main cerebral arteries; no marked focus of infarction on CT or MRI. PET was performed before and 1 month after the operation, and CBF, the cerebral metabolic rate of oxygen (CMRO{sub 2}) and oxygen extraction fraction (OEF) were analyzed. Cerebrovascular reserve capacity (CVRC) was also calculated after acetazolamide challenge. CBF during the operation was continuously measured with a thermal diffusion flow meter. CO{sub 2} response of CBF was analyzed before and after anastomosis. Neuropsychological functions were evaluated by Hasegawa dementia scale revised (HDS-R), mini-mental state examination (MMSE) and Wechsler adult intelligence scale revised (WAIS-R). Before the operation, increase in OEF accorded with the decrease in CBF, and a significant relationship between both CBF and CVRC, and OEF and CVRC was found. A decrease in CVRC was noted prior to a decrease in CBF and elevation of OEF. CVRC caused by acetazolamide might reflect CO{sub 2} reactivity. Significant improvement of CBF and CVRC, and normalization of OEF were observed after the operation. Also, significant improvement of neuropsychological function was observed by HDS-R and WAIS-R. Disturbance in neuropsychological function might reflect elevation of OEF. (author)

  9. Metabolic regulation of immune responses: therapeutic opportunities

    OpenAIRE

    Assmann, Nadine; Finlay, David K.

    2016-01-01

    Immune cell metabolism is dynamically regulated in parallel with the substantial changes in cellular function that accompany immune cell activation. While these changes in metabolism are important for facilitating the increased energetic and biosynthetic demands of activated cells, immune cell metabolism also has direct roles in controlling the functions of immune cells and shaping the immune response. A theme is emerging wherein nutrients, metabolic enzymes, and metabolites can act as an ext...

  10. Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Md Abdul Hye Khan

    Full Text Available Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN rat was transferred into the FHH genetic background (FHH.1BN. The impact of this region on cerebral arterial dilator responses remains unknown. Aminopeptidase is a gene that was transferred into the FHH genetic background to generate the FHH.1BN rats and is responsible for degradation of the vasodilator bradykinin. Thus, we hypothesized that FHH rats will have increased aminopeptidase P levels with impaired cerebral arterial responses to bradykinin compared to BN and FHH.1BN rats. We demonstrated higher cerebral arterial expression of aminopeptidase P in FHH compared to BN rats. Accordingly, we demonstrated markedly impaired cerebral arterial dilation to bradykinin in FHH compared to BN rats. Interestingly, aminopeptidase P expression was lower in FHH.1BN compared to FHH rats. Decreased aminopeptidase P levels in FHH.1BN rats were associated with increased cerebral arterial bradykinin-induced dilator responses. Aminopeptidase P inhibition by apstatin improved cerebral arterial bradykinin dilator responses in FHH rats to a level similar to FHH.1BN rats. Unlike bradykinin, cerebral arterial responses to acetylcholine were similar between FHH and FHH.1BN groups. These findings indicate decreased bradykinin bioavailability contributes to impaired cerebral arterial dilation in FHH rats. Overall, these data indicate an important role of aminopeptidase P in the impaired cerebral arterial function in FHH rat.

  11. Cerebral blood flow and metabolism for Broca's aphasia using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Toshiaki

    1987-12-01

    A total of 11 patients with Broca's aphasia (BA) underwent positron emission tomography (PET) with the purpose of investigating the responsible region and the symptomatic flow and metabolism thresholds for BA. Computed tomography (CT) was concurrently performed. In the group of 3 patients undergoing PET with C-11 glucose, both PET and CT provided abnormal findings in the region that is thought to be responsible for BA (Broca's area), including the cortex and subcortex in the anterior region to Sylvian fissure. The Broca's area in the remaining one was shown as low C-11 accumulation area on PET and as isodensity on CT. The second group, consisting of 8 BA patients and 30 control patients without BA, underwent PET using O-15 steady method. PET showed reduction of regional cerebral blood flow (rCBF) and oxygen metabolic rate (rCMRO/sub 2/) in the Broca's area in all BA patients. Computed tomography showed abnormal low density in the Broca's area in 3 patients, and abnormal findings in the basal ganglionic region and subcortex without evidence for abnormal low density in the Broca's area in the other 5 patients. Comparison of rCBF and rCMRO/sub 2/ in BA patients with those in control patients may show the symptomatic thresholds to be 20 - 27 ml100 gmin for rCBF and 2.0 ml100 gmin for rCMRO/sub 2/. (Namekawa, K.).

  12. Cerebral oxygenation and metabolism during exercise following three months of endurance training in healthy overweight males

    DEFF Research Database (Denmark)

    Seifert, T; Rasmussen, P; Brassard, P

    2009-01-01

    Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy...... overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7). Arterial and internal jugular venous catheterization was used to determine concentration differences for oxygen, glucose, and lactate across the brain and the oxygen-carbohydrate index [molar uptake of oxygen...... with a lower plasma epinephrine concentration (P exercising at 70% of maximal oxygen uptake (approximately 211 W). Before training, both OCI (3.9 +/- 0.9) and DeltaP(Mito)O(2) (-22 mmHg) decreased (P

  13. Understanding cerebral L-lysine metabolism: the role of L-pipecolate metabolism in Gcdh-deficient mice as a model for glutaric aciduria type I

    NARCIS (Netherlands)

    Posset, R.; Opp, S.; Struys, E.A.; Volkl, A.; Mohr, H.; Hoffmann, G.F.; Kolker, S.; Sauer, S.W.; Okun, J.G.

    2015-01-01

    Inherited deficiencies of the L-lysine catabolic pathway cause glutaric aciduria type I and pyridoxine-dependent epilepsy. Dietary modulation of cerebral L-lysine metabolism is thought to be an important therapeutic intervention for these diseases. To better understand cerebral L-lysine degradation,

  14. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study.

    Science.gov (United States)

    Constant, E L; de Volder, A G; Ivanoiu, A; Bol, A; Labar, D; Seghers, A; Cosnard, G; Melin, J; Daumerie, C

    2001-08-01

    Hypothyroidism is often associated with defective memory, psychomotor slowing, and depression. However, the relationship between thyroid status and cognitive or psychiatric disturbances remains unclear. Using psychometric scales, 10 patients who had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety, and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18F-labeled 2-deoxy-2fluoro-D-glucose as the tracers, to correlate the regional cerebral blood flow and cerebral glucose metabolism with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in regional cerebral blood flow (23.4%, P < 0.001) and in cerebral glucose metabolism (12.1%, P < 0.001) and there were no specific local defects. Patients were also significantly more depressed (P < 0.001), anxious (P < 0.001) and psychomotor slowed (P < 0.005) in hypo than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression.

  15. Selected Metabolic Responses to Skateboarding

    Science.gov (United States)

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  16. Bolus arrival time and cerebral blood flow responses to hypercarbia.

    Science.gov (United States)

    Donahue, Manus J; Faraco, Carlos C; Strother, Megan K; Chappell, Michael A; Rane, Swati; Dethrage, Lindsey M; Hendrikse, Jeroen; Siero, Jeroen C W

    2014-07-01

    The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution=4 × 4 × 7 mm(3); repetition time/echo time (TR/TE)=3,600/11 ms) sequentially in healthy volunteers (n=12; age=30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO₂/21% O₂/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO₂/95% O₂) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

  17. Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets

    DEFF Research Database (Denmark)

    Nielsen, Troels Halfeld; Olsen, N.V.; Toft, P

    2013-01-01

    variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis...... and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3). RESULTS: PbtO2 increased during cyanide...... metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate...

  18. Imaging cerebral tryptophan metabolism in brain tumor-associated depression.

    Science.gov (United States)

    Bosnyák, Edit; Kamson, David O; Behen, Michael E; Barger, Geoffrey R; Mittal, Sandeep; Juhász, Csaba

    2015-12-01

    Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[(11)C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD', an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. The mean BDI-II score was 12 ± 10 (range: 2-33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman's rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD' values were higher in the depressed subgroup than in non-depressed patients (p Tumor size, grade, and tumor type were not related to depression scores. Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of

  19. Developmental Sex Differences in the Metabolism of Cardiolipin in Mouse Cerebral Cortex Mitochondria

    OpenAIRE

    Acaz-Fonseca, Estefan?a; Ortiz-Rodriguez, Ana; Lopez-Rodriguez, Ana B.; Garcia-Segura, Luis M.; Astiz, Mariana

    2017-01-01

    Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In male...

  20. [A study on the cerebral glucose metabolism in progressive supranuclear palsy].

    Science.gov (United States)

    Ma, Ai-jun; Guo, Xiao-jun; Li, Da-cheng; Zhang, Ben-shu; Pan, Xu-dong

    2012-11-01

    To study the regional cerebral glucose utilization with (18)F-fluorodeoxyglucose (FDG) PET and to investigate the correlation between cerebral glucose metabolism and the clinical characteristic of progressive supranuclear palsy (PSP). A total of 13 patients with PSP and 30 matched healthy controls were performed (18)F-FDG PET imaging at rest state. Visual inspection and statistical parametric mapping (SPM) were used to investigate regional cerebral metabolic rate of glucose (rCMRglc). Based on the visual inspection, PET imaging in the PSP patients showed that the focal hypometabolic areas mainly included the bilateral frontal cortex, midbrain and subcortical structures. Compared to the controls, voxel-based analysis showed that the regional glucose metabolism decreased in bilateral superior, middle frontal gyrus, cingulate gyrus, midbrain and subcortical structures including basal ganglion and thalamus, which were consisted with the clinical characteristics, such as vertical gaze palsy, pseudobulbar palsy, postural instability, axial rigidity, dementia and so on. (18)F-FDG PET imaging is helpful for the early diagnosis of PSP.

  1. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  2. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. (Univ. of California, Irvine (USA)); Gillin, J.C. (Univ. of California, San Diego (USA))

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.

  3. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain.

    Science.gov (United States)

    Bouzat, Pierre; Sala, Nathalie; Suys, Tamarah; Zerlauth, Jean-Baptiste; Marques-Vidal, Pedro; Feihl, François; Bloch, Jocelyne; Messerer, Mahmoud; Levivier, Marc; Meuli, Reto; Magistretti, Pierre J; Oddo, Mauro

    2014-03-01

    Experimental evidence suggests that lactate is neuroprotective after acute brain injury; however, data in humans are lacking. We examined whether exogenous lactate supplementation improves cerebral energy metabolism in humans with traumatic brain injury (TBI). We prospectively studied 15 consecutive patients with severe TBI monitored with cerebral microdialysis (CMD), brain tissue PO2 (PbtO2), and intracranial pressure (ICP). Intervention consisted of a 3-h intravenous infusion of hypertonic sodium lactate (aiming to increase systemic lactate to ca. 5 mmol/L), administered in the early phase following TBI. We examined the effect of sodium lactate on neurochemistry (CMD lactate, pyruvate, glucose, and glutamate), PbtO2, and ICP. Treatment was started on average 33 ± 16 h after TBI. A mixed-effects multilevel regression model revealed that sodium lactate therapy was associated with a significant increase in CMD concentrations of lactate [coefficient 0.47 mmol/L, 95% confidence interval (CI) 0.31-0.63 mmol/L], pyruvate [13.1 (8.78-17.4) μmol/L], and glucose [0.1 (0.04-0.16) mmol/L; all p < 0.01]. A concomitant reduction of CMD glutamate [-0.95 (-1.94 to 0.06) mmol/L, p = 0.06] and ICP [-0.86 (-1.47 to -0.24) mmHg, p < 0.01] was also observed. Exogenous supplemental lactate can be utilized aerobically as a preferential energy substrate by the injured human brain, with sparing of cerebral glucose. Increased availability of cerebral extracellular pyruvate and glucose, coupled with a reduction of brain glutamate and ICP, suggests that hypertonic lactate therapy has beneficial cerebral metabolic and hemodynamic effects after TBI.

  4. Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia.

    Science.gov (United States)

    Waddington, J L

    1993-01-01

    Much evidence points to the importance of intrauterine events in the etiology of schizophrenia and suggests a complex interplay between dysfunctional and intact neurons in the pathophysiology of the disorder. This article contrasts what is known of the topographies of metabolic and structural brain abnormalities in schizophrenia at differing stages of the illness. From these contrasts, a schema is elaborated by which subtle neurodevelopmental perturbation in early to middle gestation might give rise to functional and structural abnormalities that ultimately release the diagnostic symptoms of schizophrenia. An interaction between those mechanisms mediating the expression of psychosis and the initially subtle stages of normal aging is posited to act on the substrate of a brain that is already developmentally compromised. Such a process might masquerade as "progression" in the absence of any active disease directly attributable to the original etiological event.

  5. Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia

    Directory of Open Access Journals (Sweden)

    Milovanović Aleksandar

    2012-01-01

    Full Text Available Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals

  6. Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

    Science.gov (United States)

    Molinari, F; Simonetti, V; Franzini, M; Pandolfi, S; Vaiano, F; Valdenassi, L; Liboni, W

    2014-01-01

    Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the

  7. The Impact of Venoarterial and Venovenous Extracorporeal Membrane Oxygenation on Cerebral Metabolism in the Newborn Brain.

    Directory of Open Access Journals (Sweden)

    Aaron J Reitman

    Full Text Available Extracorporeal membrane oxygenation (ECMO is an effective therapy for supporting infants with reversible cardiopulmonary failure. Still, survivors are at risk for long-term neurodevelopmental impairments, the cause of which is not fully understood.To elucidate the effects of ECMO on the newborn brain. We hypothesized that the cerebral metabolic profile of neonates who received ECMO would differ from neonates who did not receive ECMO. To address this, we used magnetic resonance spectroscopy (1H-MRS to investigate the effects of venoarterial and venovenous ECMO on cerebral metabolism.41 neonates treated with ECMO were contrasted to 38 age-matched neonates.All 1H-MRS data were acquired from standardized grey matter and white matter regions of interest using a short-echo (TE = 35 milliseconds, point-resolved spectroscopy sequence (PRESS and quantitated using LCModel. Metabolite concentrations (mmol/kg were compared across groups using multivariate analysis of covariance. Elevated creatine (p = 0.002 and choline (p = 0.005 concentrations were observed in the grey matter among neonates treated with ECMO relative to the reference group. Likewise, choline concentrations were elevated in the white matter (p = 0.003 while glutamate was reduced (p = 0.03. Contrasts between ECMO groups revealed lower osmolite concentrations (e.g. myoinositol among the venovenous ECMO group.Neonates who underwent ECMO were found to have an abnormal cerebral metabolic profile, with the pattern of abnormalities suggestive of an underlying inflammatory process. Additionally, neonates who underwent venovenous ECMO had low cerebral osmolite concentrations as seen in vasogenic edema.

  8. Clinical and metabolic correlates of cerebral calcifications in Sturge-Weber syndrome.

    Science.gov (United States)

    Pilli, Vinod K; Behen, Michael E; Hu, Jiani; Xuan, Yang; Janisse, James; Chugani, Harry T; Juhász, Csaba

    2017-09-01

    To evaluate clinical and metabolic correlates of cerebral calcifications in children with Sturge-Weber syndrome (SWS). Fifteen children (11 females, four males; age range 7mo-9y, mean 4y 1mo) with unilateral SWS underwent baseline and follow-up magnetic resonance imaging (MRI) with susceptibility weighted imaging (SWI), glucose metabolism positron emission tomography (PET), and neurocognitive assessment (mean follow-up 1y 8mo). Calcified brain volumes measured on SWI were correlated with areas of abnormal glucose metabolism, seizure variables, and cognitive function (IQ). Ten children had brain calcification at baseline and 11 at follow-up. Mean calcified brain volume increased from 1.69 to 2.47cm3 (p=0.003) in these children; the rate of interval calcified volume increase was associated with early onset of epilepsy (Spearman's rho [rs ]=-0.63, p=0.036). Calcified brain regions showed a variable degree of glucose hypometabolism with the metabolic abnormalities often extending to non-calcified cerebral lobes. Larger calcified brain volumes at baseline were associated with longer duration of epilepsy (rs =0.69, p=0.004) and lower outcome IQ (rs =-0.53, p=0.042). Brain calcifications are common and progress faster in children with SWS with early epilepsy onset, and are associated with a variable degree of hypometabolism, which is typically more extensive than the calcified area. Higher calcified brain volumes may indicate a risk for poorer neurocognitive outcome. © 2017 Mac Keith Press.

  9. Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

    Science.gov (United States)

    Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.

    2012-01-01

    Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469

  10. Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers.

    Science.gov (United States)

    Weiduschat, Nora; Kaufmann, Petra; Mao, Xiangling; Engelstad, Kristin Marie; Hinton, Veronica; DiMauro, Salvatore; De Vivo, Darryl; Shungu, Dikoma

    2014-03-04

    To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging ((1)H MRSI) and to assess their potential as prognostic biomarkers. In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with (1)H MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-l-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]). Consistent with prior studies, the patients with MELAS had higher lactate (p mutation carriers to develop the MELAS phenotype. (1)H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype.

  11. Propofol Compared to Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Atkinson, D. B.; Ledee, Dolena R.; Kayser, Ernst-Bernhard; Morgan, Phil G.; Sedensky, Margaret M.; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2014-01-08

    Anesthetics used in infants and children are implicated in development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in an immature swine model anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon labeled glucose and leucine in the common carotid artery in order to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared-spectroscopy. Compared to isoflurane, propofol depleted ATP and glycogen stores. Propofol also decreased pools of the CAC intermediates, citrate and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked accumulation of lactate. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype which resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations which typically accompany propofol infusion syndrome. These metabolic abnormalities may play a role in neurotoxity observed with propofol in the vulnerable immature brain.

  12. Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G mutation.

    Science.gov (United States)

    Lindroos, Markus M; Borra, Ronald J; Parkkola, Riitta; Virtanen, Sami M; Lepomäki, Virva; Bucci, Marco; Virta, Jere R; Rinne, Juha O; Nuutila, Pirjo; Majamaa, Kari

    2009-12-01

    The m.3243A>G mutation is the most common pathogenic mutation in mitochondrial DNA. It leads to defective oxidative phosphorylation, decreased oxygen consumption and increased glucose utilization and lactate production in vitro. However, oxygen and glucose metabolism has not been studied in the brain of patients harbouring the m.3243A>G mutation. Therefore, 14 patients with the m.3243A>G mutation, not experiencing acute stroke-like episodes and 14 age-matched controls underwent positron emission tomography using 2-[(18)F]fluoro-2-deoxyglucose, [(15)O]H(2)O and [(15)O]O(2) as the tracers during normoglycaemia. The metabolic rate of oxygen and glucose were determined using a quantitative region of interest analysis. Metabolites in unaffected periventricular tissue were measured using magnetic resonance spectroscopy. We found that the cerebral metabolic rate of oxygen was decreased by 26% (range 18%-29%) in the grey as well as the white matter of patients with the m.3243A>G mutation. A decrease in the metabolic rate of glucose was found with predilection to the posterior part of the brain. No major changes were detected in cerebral blood flow or the number of white matter lesions. Our results show that the m.3243A>G mutation leads to a global decrease in oxygen consumption in the grey matter including areas where no other signs of disease were present.

  13. Response to trauma and metabolic changes: posttraumatic metabolism.

    Science.gov (United States)

    Şimşek, Turgay; Şimşek, Hayal Uzelli; Cantürk, Nuh Zafer

    2014-01-01

    Stress response caused by events such as surgical trauma includes endocrine, metabolic and immunological changes. Stress hormones and cytokines play a role in these reactions. More reactions are induced by greater stress, ultimately leading to greater catabolic effects. Cuthbertson reported the characteristic response that occurs in trauma patients: protein and fat consumption and protection of body fluids and electrolytes because of hypermetabolism in the early period. The oxygen and energy requirement increases in proportion to the severity of trauma. The awareness of alterations in amino acid, lipid, and carbohydrate metabolism changes in surgical patients is important in determining metabolic and nutritional support. The main metabolic change in response to injury that leads to a series of reactions is the reduction of the normal anabolic effect of insulin, i.e. the development of insulin resistance. Free fatty acids are primary sources of energy after trauma. Triglycerides meet 50 to 80 % of the consumed energy after trauma and in critical illness. Surgical stress and trauma result in a reduction in protein synthesis and moderate protein degradation. Severe trauma, burns and sepsis result in increased protein degradation. The aim of glucose administration to surgical patients during fasting is to reduce proteolysis and to prevent loss of muscle mass. In major stress such as sepsis and trauma, it is important both to reduce the catabolic response that is the key to faster healing after surgery and to obtain a balanced metabolism in the shortest possible time with minimum loss. For these reasons, the details of metabolic response to trauma should be known in managing these situations and patients should be treated accordingly.

  14. T cell metabolism and the immune response.

    Science.gov (United States)

    Verbist, Katherine C; Wang, Ruoning; Green, Douglas R

    2012-12-01

    As T cells respond to pathogens, they must transition from a quiescent, naïve state, to a rapidly proliferating, active effector state, and back again to a quiescent state as they develop into memory cells. Such transitions place unique metabolic demands on the differentiating cells. T cells meet these demands by altering their metabolic profiles, which are, in turn, regulated by distinct signaling cascades and transcriptional programs. Here, we examine the metabolic profiles of T cells during an acute immune response and discuss the signal and transcriptional regulators of these metabolic changes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Factor analysis of regional cerebral glucose metabolic rates in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Szabo, Z.; Camargo, E.E.; Sostre, S.; Shafique, I.; Sadzot, B.; Links, J.M.; Dannals, R.F.; Wagner, H.N. Jr. (Johns Hopkins Medical Institutions, Baltimore, MA (United States). Div. of Nuclear Medicine Johns Hopkins Medical Institutions, Baltimore, MA (United States). Div. of Radiation Health Sciences)

    1992-07-01

    Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance. (orig.).

  16. Effects of nitrous oxide on cerebral haemodynamics and metabolism during isoflurane anaesthesia in man

    Energy Technology Data Exchange (ETDEWEB)

    Algotsson, L.; Messeter, K. (Department of Anaesthesiology, University Hospital, Lund (Sweden)); Rosen, I. (Department of Clinical Neurophysiology, University Hospital, Lund (Sweden)); Holmin, T. (Department of Surgery, University Hospital, Lund (Sweden))

    1992-01-01

    Seven normoventilated and five hyperventilated healthy adults undergoing cholecystectomy and anaesthetized with methohexitone, fentanyl and pancuronium were studied with measurement of cerebral blood flow (CBF), cereal metabolic rate of oxygen (CMRo[sub 2]), and quantified electroencephalography (EEG) under two sets of conditions: (1) 1.7% end-tidal concentration of isoflurane in air/oxygen: (2) 0.85% end-tidal concentration of isoflurane in nitrous oxide (N[sub 2]O)/oxygen. The object was to study the effects of N[sub 2]O during isoflurane anaesthesia on cerebral circulation, metabolism and neuroelectric activity. N[sub 2]O in the anaesthetic gas mixture caused a 43% (P<0.05) increase in CBF during normocarbic conditions but no significant change during hypocapnia. CMRo[sub 2] was not significantly altered by N[sub 2]O. EEG demonstrated an activated pattern with decreased low frequency activity and increased high frequency activity. The results confirm that N[sub 2]O is a potent cerebral vasodilator in man, although the mechanisms underlying the effects on CBF are still unclear. (au).

  17. Metabolic regulation of immune responses: therapeutic opportunities.

    Science.gov (United States)

    Assmann, Nadine; Finlay, David K

    2016-06-01

    Immune cell metabolism is dynamically regulated in parallel with the substantial changes in cellular function that accompany immune cell activation. While these changes in metabolism are important for facilitating the increased energetic and biosynthetic demands of activated cells, immune cell metabolism also has direct roles in controlling the functions of immune cells and shaping the immune response. A theme is emerging wherein nutrients, metabolic enzymes, and metabolites can act as an extension of the established immune signal transduction pathways, thereby adding an extra layer of complexity to the regulation of immunity. This Review will outline the metabolic configurations adopted by different immune cell subsets, describe the emerging roles for metabolic enzymes and metabolites in the control of immune cell function, and discuss the therapeutic implications of this emerging immune regulatory axis.

  18. Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria.

    Science.gov (United States)

    Villa, Roberto Federico; Ferrari, Federica; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

    2016-08-25

    Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Early cerebral metabolic crisis after TBI influences outcome despite adequate hemodynamic resuscitation.

    Science.gov (United States)

    Stein, Nathan R; McArthur, David L; Etchepare, Maria; Vespa, Paul M

    2012-08-01

    Optimal resuscitation after traumatic brain injury (TBI) remains uncertain. We hypothesize that cerebral metabolic crisis is frequent despite adequate resuscitation of the TBI patient and that metabolic crisis negatively influences outcome. We assessed the effectiveness of a standardized trauma resuscitation protocol in 89 patients with moderate to severe TBI, and determined the frequency of adequate resuscitation. Prospective hourly values of heart rate, blood pressure, pulse oximetry, intracranial pressure (ICP), respiratory rate, jugular venous oximetry, and brain extracellular values of glucose, lactate, pyruvate, glycerol, and glutamate were obtained. The incidence during the initial 72 h after injury of low brain glucose 25, and metabolic crisis, defined as the simultaneous occurrence of both low glucose and high LPR, were determined for the group. 5 patients were inadequately resuscitated and eight patients had intractable ICP. In patients with successful resuscitation and controlled ICP (n = 76), within 72 h of trauma, 76% had low glucose, 93% had elevated LPR, and 74% were in metabolic crisis. The duration of metabolic crisis was longer in those patients with unfavorable (GOSe ≤ 6) versus favorable (GOSe ≥ 7) outcome at 6 months (P = 0.011). In four multivariate models the burden of metabolic crisis was a powerful independent predictor of poor outcome. Metabolic crisis occurs frequently after TBI despite adequate resuscitation and controlled ICP, and is a strong independent predictor of poor outcome at 6 months.

  20. Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Hanafy, Khalid A; Morgan Stuart, R; Fernandez, Luis; Schmidt, J Michael; Claassen, Jan; Lee, Kiwon; Sander Connolly, E; Mayer, Stephan A; Badjatia, Neeraj

    2010-01-01

    Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt-Hess grade 4-5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5-3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1-4.8), aneurysm size >10mm (OR 1.7, 95% CI 1.1-2.6), body temperature 38.3 degrees C (OR 2.5, 95% CI 1.1-5.4), and hyperglycemia >200mg/dL (OR 2.7, 95% CI 1.6-4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt-Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  1. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

    2001-04-01

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

  2. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-05-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism.

  3. Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

    1987-03-01

    Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO/sub 2/) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO/sub 2/, and oxygen extraction fraction were measured by the positron emission tomography using /sup 15/O/sub 2/, C/sup 15/O/sub 2/ inhalation technique. In addition to reduction of CBF and CMRO/sub 2/ in the basal ganglionic region, CBF and CMRO/sub 2/ decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO/sub 2/ decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO/sub 2/ was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO/sub 2/ were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia.

  4. Cerebral metabolic changes in neurologically presymptomatic patients undergoing haemodialysis: in vivo proton MR spectroscopic findings

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Ming-Lun; Chiang, I. Chan [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Li, Chun-Wei [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Chang, Jer-Ming [Kaohsiung Medical University, Department of Internal Medicine, Kaohsiung Hsiao-Kang Municipal Hospital (China); Kaohsiung Medical University, Department of Nephrology, School of Medicine, College of Medicine (China); Ko, Chih-Hung [Kaohsiung Medical University, Department of Psychiatry, School of Medicine, College of Medicine (China); Kaohsiung Medical University Hospital, Department of Psychiatry (China); Chuang, Hung-Yi [Kaohsiung Medical University, Faculty of Public Health, College of Health Science (China); Kaohsiung Medical University Hospital, Department of Environmental and Occupational Medicine (China); Sheu, Reu-Sheng [Kaohsiung Medical University, Department of Radiology, Kaohsiung Municipal Hsiao-Kang Hospital (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Lee, Chen-Chang [Kaohsiung Medical University, Department of Medical Imaging and Radiological Sciences, College of Health Science (China); Kaohsiung Medical Centre, Department of Radiology, Chang Gung Memorial Hospital (China); Hsieh, Tsyh-Jyi [Kaohsiung Medical University Hospital, Department of Medical Imaging (China); Kaohsiung Medical University, Department of Radiology, Faculty of Medicine, College of Medicine (China); Kaohsiung Municipal Ta-Tung Hospital, Department of Medical Imaging (China)

    2010-06-15

    To prospectively investigate and detect early cerebral metabolic changes in patients with end-stage renal disease (ESRD) by using in vivo proton MR spectroscopy (MRS). We enrolled 32 patients with ESRD and 32 healthy controls between the ages of 26 and 50 years. Short echo time single-voxel proton MRS was acquired from volumes of interest (VOIs) located in the frontal grey and white matter, temporal white matter and basal ganglia. The choline/phospatidylcholine (Cho), myo-inositol (mI), N-acetylaspartate (NAA) and total creatine (tCr) peaks were measured and the metabolic ratios with respect to tCr were calculated. In the ESRD group, significant elevations of the Cho/tCr and mI/tCr ratios were observed for the frontal grey matter, frontal white matter, temporal white matter and basal ganglia as compared with controls. There was no significant difference in the NAA/tCr ratios at all VOIs between the ESRD patients and the healthy controls. Proton MRS is a useful and non-invasive imaging tool for the detection of early cerebral metabolic changes in neurologically presymptomatic ESRD patients. (orig.)

  5. Blast overpressure waves induce transient anxiety and regional changes in cerebral glucose metabolism and delayed hyperarousal in rats

    Directory of Open Access Journals (Sweden)

    Hibah Omar Awwad

    2015-06-01

    Full Text Available Physiological alterations, anxiety and cognitive disorders are strongly associated with blast-induced traumatic brain injury (blast TBI and are common symptoms in service personnel exposed to blasts. Since 2006, 25-30,000 new TBI cases are diagnosed annually in U.S. Service members; increasing evidence confirms that primary blast exposure causes diffuse axonal injury and is often accompanied by altered behavioral outcomes. Behavioral and acute metabolic effects resulting from blast to the head in the absence of thoracic contributions from the periphery were examined following a single blast wave directed to the head of male Sprague-Dawley rats protected by a lead shield over the torso. An 80 psi head blast produced cognitive deficits that were detected in working memory. Blast TBI rats displayed increased anxiety as determined by elevated plus maze at day 9 post-blast compared to sham rats; blast TBI rats spent significantly more time than the sham controls in the closed arms (p<0.05; n=8-11. Interestingly, anxiety symptoms were absent at days 22 and 48 post-blast. Instead, blast TBI rats displayed hyperactivity and increased rearing behavior at day 48 post-blast compared to sham rats. Blast TBI rats also exhibited suppressed acoustic startle responses, but similar pre-pulse inhibition at day 15 post-blast compared to sham rats. Acute physiological alterations in cerebral glucose metabolism were determined by positron emission tomography 1 and 9 days post-blast using F-18-fluorodeoxyglucose. Global glucose uptake in blast TBI rat brains increased at day 1 post-blast (p<0.05; n=4-6 and returned to sham levels by day 9. Our results indicate a transient increase in cerebral metabolism following a blast injury. Markers for reactive astrogliosis and neuronal damage were noted by immunoblotting motor cortex tissue from day 10 post-blast in blast TBI rats compared to sham controls (p<0.05; n=5-6.

  6. Cerebral blood flow response to propranolol in streptozotocin diabetic rats

    DEFF Research Database (Denmark)

    Lass, Preben; Knudsen, G M

    1990-01-01

    The influence of propranolol on cerebral blood flow (CBF) was tested in streptozotocin diabetic rats and in control animals. Resting CBF values were 40% lower in the diabetic rats compared with controls. Intravenous injection of propranolol (2 mg kg-1) decreased CBF significantly in the control...... group; the CBF decreased for 15 min after propranolol injection and returned to baseline values after 90 min. In the diabetic rats, the CBF declined steadily but this decrease did not reach significance, even after 90 min. Impaired beta-adrenergic mechanisms may be an important factor in the CBF...... alterations which occur in diabetes mellitus. Further, it is suggested that an impaired CBF response may play a role in CNS lesions in diabetic patients treated with beta antagonists....

  7. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  8. Cerebral Blood Flow Responses to Aquatic Treadmill Exercise.

    Science.gov (United States)

    Parfitt, Rhodri; Hensman, Marianne Y; Lucas, Samuel J E

    2017-07-01

    Aquatic treadmills are used as a rehabilitation method for conditions such as spinal cord injury, osteoarthritis, and stroke, and can facilitate an earlier return to exercise training for athletes. However, their effect on cerebral blood flow (CBF) responses has not been examined. We tested the hypothesis that aquatic treadmill exercise would augment CBF and lower HR compared with land-based treadmill exercise. Eleven participants completed incremental exercise (crossover design) starting from walking pace (4 km·h, immersed to iliac crest [aquatic], 6 km·h [land]) and increasing 1 km·h every 2 min up to 10 km·h for aquatic (maximum belt speed) or 12 km·h for land. After this, participants completed two 2-min bouts of exercise immersed to midthigh and midchest at constant submaximal speed (aquatic), or were ramped to exhaustion (land; increased gradient 2° every min). Middle cerebral artery blood flow velocity (MCAv) and HR were measured throughout, and the initial 10 min of each protocol and responses at each immersion level were compared. Compared with land-based treadmill, MCAvmean increased more from baseline for aquatic exercise (21% vs 12%, P aquatic walking compared with land-based moderate intensity running (~10 cm·s, P = 0.56). Greater water immersion lowered HR (139 vs 178 bpm for midchest vs midthigh), whereas MCAvmean remained constant (P = 0.37). Findings illustrate the potential for aquatic treadmill exercise to enhance exercise-induced elevations in CBF and thus optimize shear stress-mediated adaptation of the cerebrovasculature.

  9. Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Foged, Eva M; Krogh-Madsen, Rikke

    2010-01-01

    exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young males (18-34 yo., 74 +/- 7 kg) received either 3 days of high dose (30,000 IU day(-1), N=7) double-blinded placebo controlled or 3 months of low dose (5,000 IU week(-1), N=8) counter-balanced open but controlled...... activation by transcranial magnetic stimulation-induced twitch force were evaluated. Although EPO in a high dose increased cerebrospinal fluid EPO concentration ~20-fold and affected ventilation and cerebral glucose and lactate metabolism (P... on cognition, voluntary activation or exercise capacity but ratings of perceived exertion increased (P

  10. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    Energy Technology Data Exchange (ETDEWEB)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  11. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

    1987-09-01

    Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.

  12. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

    Energy Technology Data Exchange (ETDEWEB)

    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  13. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat.

    Science.gov (United States)

    Mraovitch, S; Calando, Y; Goadsby, P J; Seylaz, J

    1992-06-01

    Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with alpha-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical (frontal, parietal and occipital) lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate, for the first time, that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome.

  14. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S. [Asan Medical Center, Seoul (Korea, Republic of)

    2007-07-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2{approx}10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2{approx}6 years) and older (7{approx}10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20{approx}30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI.

  15. A five-year longitudinal study of the regional cerebral metabolic changes of a schizophrenic patient from the first episode using Tc-99m HMPAO SPECT.

    Science.gov (United States)

    Chen, R Y; Chen, E; Ho, W Y

    2000-01-01

    This is a naturalistic study of the relationship between cerebral metabolic activity, clinical symptoms and treatment response in a schizophrenic patient for 5 years from the onset of her illness. Serial technetium-99m-HMPAO brain SPECT was used to measure regional cerebral metabolism. The Cambridge Neurological Inventory and neuropsychological tests (WAIS-R verbal subscales, Wisconsin Card Sorting Test, semantic verbal fluency, logical memory in Weschler Memory Scale) were used for neurocognitive assessment. Under-activity of the left temporal area was observed in the course of patient illness despite remission of the psychotic symptoms. Bilateral prefrontal metabolic under-activity was noted at the emergence of negative symptoms, executive neurocognitive dysfunction and the treatment-resistant state. After response to clozapine, the right prefrontal activity returned to a normal level. Our findings suggested that persistent left temporal underactivity detected by SPECT despite clinical remission may indicate a vulnerability for further relapses and development of a treatment-resistant state. Treatment-resistant state, negative symptoms and executive neurocognitive deficit may involve abnormal prefrontal metabolic activity and can be alleviated in clozapine-responsive patients.

  16. Fibrinogen metabolic responses to trauma

    Directory of Open Access Journals (Sweden)

    Martini Wenjun

    2009-01-01

    Full Text Available Abstract Coagulation complications are significant contributors to morbidity and mortality in trauma patients. Although the lethal triad of hypothermia, acidosis and coagulopathy has been recognized for over a decade, the underlying mechanisms related to the development of coagulopathy remain unclear. Recent data suggest that decreased fibrinogen levels contribute to the development of coagulation disorders. Thus, regulation of fibrinogen availability, not fully understood at present, may play an important role in survival of trauma patients. This review summarizes the recent findings of the studies that have explored mechanisms related to changes in fibrinogen availability following trauma-related events. Trauma alters fibrinogen metabolism in a variety of ways: hemorrhage – accelerated fibrinogen breakdown; hypothermia – inhibited fibrinogen synthesis; and, acidosis – accelerated fibrinogen breakdown. However, hemorrhage, hypothermia andcidosis all result in a consistent outcome of fibrinogen availability deficit, supporting the notion of fibrinogen supplementation in trauma patients with coagulation defects. Future prospective clinical trials are needed to confirm the beneficial effects of fibrinogen supplementation in trauma patients with bleeding complications.

  17. Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

    Science.gov (United States)

    Patet, Camille; Quintard, Hervé; Suys, Tamarah; Bloch, Jocelyne; Daniel, Roy T; Pellerin, Luc; Magistretti, Pierre J; Oddo, Mauro

    2015-10-15

    Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

  18. Metabolic Responses to Weight Lifting

    Directory of Open Access Journals (Sweden)

    Arnold Nelson

    2017-04-01

    Full Text Available Editor's Note, The ability to lift heavy loads while performing multiple repetitions is not only highly correlated with muscle mass or the total number actomyosin interactions, but also metabolic functions that includes substrate concentrations and by-product removal.  Muscles use adenosine triphosphate (ATP in at least three locations during exercise; to run the actomyosin interaction, operate sarcoplasmic reticulum calcium pumps, and operate sarcolemma sodium and potassium pumps.  Weight lifting sessions are considered to be an intermittent activity that includes only a few second bursts of high force and/or velocity movements followed by rest periods of up to several minutes. Therefore, the anaerobic pathways such as the phosphagen and glycolytic systems are the initial pathways to respond due in part to the ability to match the increased rates of ATP depletion by increasing ATP production. After the initial resting ATP stores are used up, the phosphagen system starts contributing to ATP replenishment.  This system consists of reactions from the creatine kinase (CK pathway and the adenylate kinase (AK pathway.  However, the CK pathway can only work at max capacity for a short period for resting phosphocreatine (PCr concentrations are only about 4-6 times the amount of resting ATP stores.  Once the PCr concentrations are depleted, the AK reaction will begin by using two adenosine diphosphate (ADP to form one ATP and one adenosine monophosphate (AMP. Although ATP is produced in this pathway, this production of ATP does coincide with an increased concentration of AMP. This is problematic because increased AMP levels will in turn stimulate the adenylate deaminase reaction, which will produce ammonia (NH3. This conversion of AMP into NH3 will result in the muscle cell having a net loss of total adenine nucleotides available to resynthesize ATP.  Glycolysis is the next reaction in line, which increases its role in ATP replenishment as PCr

  19. The metabolism of C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats.

    Science.gov (United States)

    Thoren, Anna E; Helps, Stephen C; Nilsson, Michael; Sims, Neil R

    2006-05-01

    To provide insights into the effects of temporary focal ischemia on the function of neurons and astrocytes in vivo, we measured the incorporation of radiolabel from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h. Under the experimental conditions used, 14C-glutamate is mainly produced in neurons whereas 14C-glutamine is generated in astrocytes from 14C-glutamate of both neuronal and astrocytic origin. Radiolabel incorporation into both amino acids was greatly decreased. The change in 14C-glutamate accumulation provides strong evidence for substantial reductions in neuronal glucose metabolism. The resulting decrease in delivery of 14C-glutamate from the neurons to astrocytes was probably also the major contributor to the change in 14C-glutamine content. These alterations probably result in part from a marked depression of glycolytic activity in the neurons, as suggested by previous studies assessing deoxyglucose utilization. Alterations in 14C-glucose metabolism were not restricted to tissue that would subsequently become infarcted. Thus, these changes did not inevitably lead to death of the affected cells. The ATP : ADP ratio and phosphocreatine content were essentially preserved during recirculation following 2 h of ischemia and showed at most only moderate losses in some subregions following 3 h of ischemia. This retention of energy reserves despite the decreases in 14C-glucose metabolism in neurons suggests that energy needs were substantially reduced in the post-ischemic brain. Marked increases in tissue lactate accumulation during recirculation, particularly following 3 h of ischemia, provided evidence that impaired pyruvate oxidation probably also contributed to the altered 14C-glucose metabolism. These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to

  20. Cocaine abstinence following chronic treatment alters cerebral metabolism in dopaminergic reward regions. Bromocriptine enhances recovery

    Energy Technology Data Exchange (ETDEWEB)

    Clow, D.W.; Hammer, R.P. Jr. (Univ. of Hawaii School of Medicine, Honolulu (USA))

    1991-01-01

    2-(14C)deoxyglucose autoradiography was used to determine local cerebral glucose utilization (lCGU) in rats following chronic cocaine treatment and subsequent abstinence. lCGU was examined in 43 discrete brain regions in animals which had received daily injections of cocaine for 14 days (10 mg/kg) followed by 3 days of saline or bromocriptine (10 mg/kg) treatment. Cocaine abstinence following chronic treatment significantly reduced lCGU in several regions including mesocorticolimbic structures such as ventral tegmental area, medial prefrontal cortex, and nucleus accumbens (NAc). Within the NAc, however, only the rostral pole showed significant reduction. In contrast, when bromocriptine treatment accompanied abstinence, lCGU was no longer reduced in mesocorticolimbic and most other regions, implying that metabolic recovery was enhanced by bromocriptine treatment during early abstinence following chronic cocaine treatment. These data suggest that cerebral metabolism is decreased during cocaine abstinence following chronic treatment in critical brain regions, and that this alteration can be prevented by treatment with direct-acting dopamine agonists such as bromocriptine.

  1. Cerebral blood flow and oxygen metabolism in dementia with Lewy bodies

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoshitomo; Takahashi, Satoshi; Yonezawa, Hisashi [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2000-06-01

    Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO{sub 2}) and the oxygen extraction fraction (rOEF) were measured using the steady-state {sup 15}O technique and positron emission tomography (PET) in six patients with dementia with Lewy bodies (DLB), and compared with ten patients with Alzheimer disease (AD) and six normal controls. In the AD patients, rCBF and rCMRO{sub 2} were significantly decreased in the frontal, parietal, and temporal cortices compared with controls. In DLB patients, rCBF and rCMRO{sub 2} were decreased in the frontal, parietal, temporal, and occipital cortices compared with controls, and were decreased more diffusely than in AD patients. rCBF and rCMRO{sub 2} were significantly decreased in occipital cortex compared with AD patients. rOEF was significantly increased in the parieto-temporal cortex in AD patients compared with controls. In DLB patients, rOEF was significantly increased not only in the parieto-temporal cortex but also in the occipital and frontal cortices compared with controls, and was significantly increased in the occipital cortex compared with AD patients. The diffuse reduction of cerebral blood flow and oxygen metabolism including the occipital cortex may be related to visual hallucination and other visuospatial deficits frequently seen in DLB patients. The increase in rOEF may be mainly due to the reduction in the vascular bed associated with decreased activity in the vasodilatory cholinergic system. (author)

  2. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    Science.gov (United States)

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  3. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi [Gunma Univ., Maebashi (Japan). School of Medicine; Hirai, Shunsaku

    1998-04-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease`s natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO{sub 2}). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman`s rank correlation coefficients. A general reduction in rCBF and rCMRO{sub 2} in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO{sub 2}. A correlation between the decrease in rCMRO{sub 2} and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  4. Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex.

    Science.gov (United States)

    Villa, Roberto Federico; Gorini, Antonella; Hoyer, Siegfried

    2009-12-01

    mitochondria seems to be more affected in aged animals. These data allow the hypothesis that the observed modifications of catalytic activities in non-synaptic and intra-synaptic mitochondrial enzyme systems linked to energy metabolism, amino acids and glutamate metabolism are primary responsible for the physiopathological responses of cerebral tissue to complete cerebral ischemia for 15 min duration during ageing.

  5. Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa

    Directory of Open Access Journals (Sweden)

    Christina E. Wierenga

    2017-07-01

    Full Text Available The etiology of pathological eating in anorexia nervosa (AN remains poorly understood. Cerebral blood flow (CBF is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW when hungry (after a 16-h fast and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry − Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex (pcorr < 0.05 and left posterior insula (punc < 0.05; RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry − Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat.

  6. Sociability trait and regional cerebral oxidative metabolism in rats: Predominantly nonlinear relations.

    Science.gov (United States)

    Kanarik, Margus; Harro, Jaanus

    2018-01-30

    Deficits in social behaviour are common in psychopathological conditions e.g., depression, autism and schizophrenia. In rats, sociability, defined as the engagement of an animal in non-aggressive social contact with a conspecific in a neutral arena, is as a persistent trait. To elucidate the neuroanatomy of social behaviour in animal models, long term neuronal energy metabolism was studied in rats preselected for sociability levels. Rats were divided into groups with high, medium and low sociability levels (HS, MS and LS) according to the average score of three social interaction tests, and cerebral long-term energy metabolism was assayed with cytochrome oxidase histochemistry. In the dorsomedial caudate putamen oxidative metabolism was linearly dependent on sociability, with LS-rats having the highest levels. In median preoptic nucleus, posterior paraventricular thalamus and median raphe, nonlinear relations appeared, HS- and LS-rats having lower oxidative activity than MS-animals. In the supraoptic nucleus MS-rats displayed lower oxidative activity than HS- and LS-animals. Intra-individual variability in social interaction on different testing occasions correlated positively with oxidative metabolism in the prelimbic cortex, bed nucleus of stria terminalis and caudate putamen, and negatively in the nucleus accumbens core. Conclusively, rats with different sociability levels are distinguished by long-term energy metabolism in nuclei involved in motivational behaviour, fear and vigilance; the relationship between energy metabolism and sociability appears to be predominantly nonlinear - animals with high and low expression of sociability are similarly deviant from the average; and intra-individual variability in social interaction is related to brain areas controlling motivation, stress reactivity and anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Directory of Open Access Journals (Sweden)

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  8. Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA.

    Science.gov (United States)

    Penet, Marie-France; Kober, Frank; Confort-Gouny, Sylviane; Le Fur, Yann; Dalmasso, Christiane; Coltel, Nicolas; Liprandi, Agnès; Gulian, Jean-Marc; Grau, Georges E; Cozzone, Patrick J; Viola, Angèle

    2007-05-11

    Malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. Severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. Using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of Plasmodium berghei ANKA on brain, in a mouse strain developing malaria but resistant to cerebral malaria. The purpose was to determine whether the infection could cause a brain dysfunction distinct from the classic cerebral syndrome. Mice resistant to cerebral malaria were infected with P. berghei ANKA and explored during both the symptomless and the severe stage of the disease by using in vivo brain magnetic resonance imaging and spectroscopy. The infected mice did not present the lesional and metabolic hallmarks of cerebral malaria. However, brain dysfunction caused by anemia, parasite burden, and hepatic damage was evidenced. We report an increase in cerebral blood flow, a process allowing temporary maintenance of oxygen supply to brain despite anemia. Besides, we document metabolic anomalies affecting choline-derived compounds, myo-inositol, glutamine, glycine, and alanine. The choline decrease appears related to parasite proliferation. Glutamine, myo-inositol, glycine, and alanine variations together indicate a hepatic encephalopathy, a finding in agreement with the liver damage detected in mice, which is also a feature of the human disease. These results reveal the vulnerability of brain to malaria infection at the severe stage of the disease even in the absence of cerebral malaria.

  9. Serum homocysteine level in patients with acute cerebral infarction and its correlation with inflammatory factors, nerve factors and NO metabolism

    Directory of Open Access Journals (Sweden)

    Zhi-Guo Li1

    2017-05-01

    Full Text Available Objective: To study the serum homocysteine (Hcy level in patients with acute cerebral infarction and its correlation with inflammatory factors, nerve factors and NO metabolism. Methods: A total of 118 patients with acute cerebral infarction were selected as observation group and 50 healthy volunteers who received physical examination in our hospital during the same period were selected as the normal control group. Serum levels of Hcy in two groups were detected, and the median of Hcy levels in observation group was referred to further divide them into high Hcy group and low Hcy group, 59 cases in each group. Serum contents of inflammatory factors, nerve factors and NO metabolism markers were compared between acute cerebral infarction patients with different levels of Hcy. Results: Serum Hcy level in observation group was higher than that in control group. Serum contents of inflammatory factors such as IL-1β, IL-6, IL-17 and hs-CRP in high Hcy group were higher than those in low Hcy group, contents of nerve factors such as Copeptin, NT-proBNP, NSE and S-100B in high Hcy group were higher than those in low Hcy group, and contents of NO metabolism indexes such as NO and NOS in high Hcy group were higher than those in low Hcy group. Conclusion: Serum Hcy level increases in patients with acute cerebral infarction, and the level of Hcy is directly related to inflammatory factors, nerve factors and NO metabolism.

  10. Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET)

    NARCIS (Netherlands)

    Vollenweider, FX; Maguire, RP; Leenders, KL; Mathys, K; Angst, J

    1998-01-01

    The effects of high euphorigenic doses of D-amphetamine (0.9-1.0 mg/kg p.o.) on regional cerebral glucose metabolism (rCMRglu) and psychological measures were investigated in 10 healthy human volunteers using a within-subject design and [F-18]-fluorodeoxygrucose positron emission tomography

  11. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    NARCIS (Netherlands)

    Verfaillie, S.C.J.; Adriaanse, S.M.; Binnewijzend, M.A.A.; Benedictus, M.R.; Ossenkoppele, R.; Wattjes, M.P.; Pijnenburg, Y.A.L.; van der Flier, W.M.; Lammertsma, A.A.; Kuijer, J.P.A.; Boellaard, R.; Scheltens, P.; van Berckel, B.N.M.; Barkhof, F.

    2015-01-01

    Objectives: Alzheimer’s disease (AD) and frontotemporal (FTD) dementia can be differentiated using [18F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD.

  12. Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function

    DEFF Research Database (Denmark)

    Bailey, D M; Evans, K A; James, P E

    2008-01-01

    We tested the hypothesis that dynamic cerebral autoregulation (CA) and blood-brain barrier (BBB) function would be compromised in acute mountain sickness (AMS) subsequent to a hypoxia-mediated alteration in systemic free radical metabolism. Eighteen male lowlanders were examined in normoxia (21% O...

  13. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M

    2013-01-01

    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this eff...

  14. Impact of Nutrition on Cerebral Circulation and Cognition in the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Laura Mellendijk

    2015-11-01

    Full Text Available The increasing prevalence of Metabolic Syndrome (MetS, defined as the clustering of abdominal obesity, dyslipidemia, hypertension, and hyperglycemia, appears to be driving the global epidemics cardiovascular disease (CVD and type 2 diabetes mellitus (T2DM. Nutrition has a major impact on MetS and plays an important role in the prevention, development, and treatment of its features. Structural and functional alterations in the vasculature, associated with MetS, might form the link between MetS and the increased risk of developing CVD and T2DM. Not only does the peripheral vasculature seem to be affected, but the syndrome has a profound impact on the cerebral circulation and thence brain structure as well. Furthermore, strong associations are shown with stroke, cognitive impairment, and dementia. In this review the impact of nutrition on the individual components of MetS, the effects of MetS on peripheral and cerebral vasculature, and its consequences for brain structure and function will be discussed.

  15. Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes

    Energy Technology Data Exchange (ETDEWEB)

    Candura, S.M.; Castoldi, A.F.; Costa, L.G. (Univ. of Washington, Seattle (United States) Fondazione Clinica del Lavoro, Pavia (Italy)); Manzo, L. (Univ. of Pavia (Italy) Fondazione Clinica del Lavoro, Pavia (Italy))

    1991-01-01

    Al, complexed with fluoride to form fluoroaluminate (AlF{sub 4}-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study the authors investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated ({sup 3}H)inositol phosphates (({sup 3}H)InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA). Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic. However, the stimulatory effects of AlCl{sub 3} and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA. In the nervous tissue, activation of PtdIns hydrolysis by Al may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C.

  16. Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men.

    Science.gov (United States)

    Hashimoto, Takeshi; Tsukamoto, Hayato; Takenaka, Saki; Olesen, Niels D; Petersen, Lonnie G; Sørensen, Henrik; Nielsen, Henning B; Secher, Niels H; Ogoh, Shigehiko

    2018-01-03

    High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine differences across the brain for lactate (a-v diff lactate ), glucose (diff glucose ), oxygen (diff oxygen ), and brain-derived neurotrophic factor (BDNF; diff BDNF ). EF was evaluated by the color-word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a-v diff glucose was unchanged, whereas the a-v diff BDNF increased similarly after both HIIEs, and the a-v diff lactate increased, but the increase was attenuated after the second HIIE, compared with the first HIIE ( P Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sørensen, H., Nielsen, H. B., Secher, N. H., Ogoh, S. Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men.

  17. Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects

    Science.gov (United States)

    Durduran, Turgut; Zhou, Chao; Buckley, Erin M.; Kim, Meeri N.; Yu, Guoqiang; Choe, Regine; Gaynor, J. William; Spray, Thomas L.; Durning, Suzanne M.; Mason, Stefanie E.; Montenegro, Lisa M.; Nicolson, Susan C.; Zimmerman, Robert A.; Putt, Mary E.; Wang, Jiongjiong; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Licht, Daniel J.

    2010-05-01

    We employ a hybrid diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) monitor for neonates with congenital heart disease (n=33). The NIRS-DCS device measured changes during hypercapnia of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations; cerebral blood flow (rCBFDCS); and oxygen metabolism (rCMRO2). Concurrent measurements with arterial spin-labeled magnetic resonance imaging (rCBFASL-MRI, n=12) cross-validate rCBFDCS against rCBFASL-MRI, showing good agreement (R=0.7, p=0.01). The study demonstrates use of NIRS-DCS on a critically ill neonatal population, and the results indicate that the optical technology is a promising clinical method for monitoring this population.

  18. Regional cerebral metabolic rate for glucose and cerebrospinal fluid monoamine metabolites in subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, Kazuhiko; Miyabayashi, Shigeaki; Iinuma, Kazuie; Tada, Keiya; Fukuda, Hiroshi; Ito, Masatoshi; Matsuzawa, Taiju

    1987-06-01

    Regional cerebral metabolic rate for glucose (rCMRglu) and cerebrospinal fluid monoamine metabolites were measured in two cases of subacute sclerosing panencephalitis (SSPE) with different clinical courses. A marked decrease in rCMRglu was found in the cortical gray matter of a patient with rapidly developing SSPE (3.6 - 4.2 mg/100 g brain tissue/min). However, the rCMRglu was preserved in the caudate and lenticular nuclei of the patient (7.7 mg/100 g/min). The rCMRglu in a patient with slowly developing SSPE revealed patterns and values similar to those of the control. Cerebrospinal fluid monoamine metabolites ; homovanilic acid and 5-hydroxyindoleacetic acid, were decreased in both rapidly and slowly developing SSPE. These data indicated that rCMRglu correlated better with the neurological and psychological status and that dopaminergic and serotonergic abnormalities have been implicated in pathophysiology of SSPE.

  19. Features of Metabolic Processes in Children Born by Caesarean Section in the Early Adaptation Period: the Role of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Т. S. Tumaeva

    2015-01-01

    Full Text Available Background: The postnatal adaptation comprises alteration of metabolic processes of a newborn, the disturbance of which can lead to dysfunction, and later — to the development of diseases. Objective: Our aim was to study the bond of cerebral ischemia in full-term children born by Caesarean section with the course of metabolic processes in the early neonatal period. Methods: A retrospective comparative study was conducted. Children born by Caesarean section, who had cerebral ischemia (n =120 and who didn't have it, (n = 150 were examined. Complex examination included an assessment of a number of factors: clinical, biochemical blood tests, acidbase balance, concentration of some hormones. Results: In children after Caesarean section with cerebral ischemia in the early period of adaptation we noted disturbances of the acid-base balance (BE 0.3 ± 1.9 mmol/l; р = 0.038, blood oxygenation (SaO2 79.7 ± 2.8%; р = 0.001, frank lactataemia (4.3 ± 1.8 mmol/l; р = 0.002, signs of a catabolic orientation of metabolism (hypoproteinemia, increased protein metabolism products, frank primary loss of body weight. The considerable changes of activity of the blood enzymes, disturbance of glucose metabolism indicated the lack of energy-dependent processes. Due to this, the hyperbilirubinemia and a hormonal imbalance were more often formed. Conclusion: Cerebral ischemia in children born by Caesarean section is a reason for the development of a metabolic disadaptation. The detection of disturbances of metabolic processes in the early neonatal period is necessary for a timely start of the correctional therapy in order to prevent the development of diseases in more distant periods of a child's life. 

  20. Alterations in cerebral metabolism observed in living rodents using fluorescence lifetime microscopy of intrinsic NADH (Conference Presentation)

    Science.gov (United States)

    Yaseen, Mohammad A.; Sakadžić, Sava; Sutin, Jason; Wu, Weicheng; Fu, Buyin; Boas, David A.

    2017-02-01

    Monitoring cerebral energy metabolism at a cellular level is essential to improve our understanding of healthy brain function and its pathological alterations. In this study, we resolve specific alterations in cerebral metabolism utilizing minimally-invasive 2-Photon fluorescence lifetime imaging (2P-FLIM) measurements of reduced nicotinamide adenine dinucleotide (NADH) fluorescence, collected in vivo from anesthetized rats and mice. Time-resolved lifetime measurements enables distinction of different components contributing to NADH autofluorescence. These components reportedly represent different enzyme-bound formulations of NADH. Our observations from this study confirm the hypothesis that NADH FLIM can identify specific alterations in cerebral metabolism. Using time-correlated single photon counting (TCSPC) equipment and a custom-built multimodal imaging system, 2-photon fluorescence lifetime imaging (FLIM) was performed in cerebral tissue with high spatial and temporal resolution. Multi-exponential fits for NADH fluorescence lifetimes indicate 4 distinct components, or 'species.' We observed distinct variations in the relative proportions of these components before and after pharmacological-induced impairments to several reactions involved in anaerobic glycolysis and aerobic oxidative metabolism. Classification models developed with experimental data correctly predict the metabolic impairments associated with bicuculline-induced focal seizures in separate experiments. Compared to traditional intensity-based NADH measurements, lifetime imaging of NADH is less susceptible to the adverse effects of overlying blood vessels. Evaluating NADH measurements will ultimately lead to a deeper understanding of cerebral energetics and its pathology-related alterations. Such knowledge will likely aid development of therapeutic strategies for neurodegenerative diseases such as Alzheimer's Disease, Parkinson's disease, and stroke.

  1. Knee jerk responses in infants at high risk for cerebral palsy : an observational EMG study

    NARCIS (Netherlands)

    Hamer, Elisa G.; Dijkstra, Linze J.; Hooijsma, Siebrigje J.; Zijdewind, Inge; Hadders-Algra, Mijna

    BACKGROUND: Following our clinical observation of tonic responses in response to the knee jerk in infants at very high risk for cerebral palsy (VHR infants), we systematically studied tonic responses, clonus, and reflex irradiation. We questioned (i) whether these responses occurred more often in

  2. Knee jerk responses in infants at high risk for cerebral palsy: an observational EMG study

    NARCIS (Netherlands)

    Hamer, E.G.; Dijkstra, L.J.; Hooijsma, S.J.; Zijdewind, I.; Hadders-Algra, M.

    2016-01-01

    BACKGROUND: Following our clinical observation of tonic responses in response to the knee jerk in infants at very high risk for cerebral palsy (VHR infants), we systematically studied tonic responses, clonus, and reflex irradiation. We questioned (i) whether these responses occurred more often in

  3. Metabolic features of the cell danger response.

    Science.gov (United States)

    Naviaux, Robert K

    2014-05-01

    The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

  4. Distinct inflammatory responses differentiate cerebral infarct from transient ischaemic attack.

    Science.gov (United States)

    Armstrong, Christopher W L; Bosio, Erika; Neil, Claire; Brown, Simon G A; Hankey, Graeme J; Fatovich, Daniel M

    2017-01-01

    We previously reported on a 26-year-old patient who presented early during a large and eventually fatal cerebral infarct. Microarray analysis of blood samples from this patient demonstrated initially up-regulated and subsequently down-regulated Granzyme B (GzmB) expression, along with progressive up-regulation of genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase 9 (MMP-9). To confirm these findings, we investigated these parameters in patients with suspected stroke presenting within 6h of symptom onset to a single centre. Blood samples were taken at enrolment, then 1h, 3h and 24h post-enrolment for the examination of cellular, protein and genetic changes. Patients with subsequently confirmed ischaemic (n=18) or haemorrhagic stroke (n=11) showed increased intracellular concentrations of GzmB in all cell populations investigated (CD8+, CD8- and Natural Killer [NK] cells). Infarct patients, however, demonstrated significantly reduced GzmB gene expression and increased circulating MMP-9 and S100A12 levels in contrast to transient ischaemic attack (TIA) patients or healthy controls. Furthermore, a pronounced neutrophilia was noted in the infarct and haemorrhage groups, while TIA patients (n=9) reflected healthy controls (n=10). These findings suggest a spectrum of immune response during stroke. TIA showed few immunological changes in comparison to infarct and haemorrhage, which demonstrated inhibition of GzmB production and a rise in neutrophil numbers and neutrophil-associated mediators. This implies a greater role of the innate immune system. These markers may provide novel targets for inhibition and reduction of secondary injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Effects of caprylic triglyceride on cognitive performance and cerebral glucose metabolism in mild Alzheimer's disease: a single-case observation.

    Science.gov (United States)

    Farah, Brian Andrew

    2014-01-01

    To examine the effect of 109 days of caprylic triglyceride (CT) in a 70-year-old male with mild Alzheimer's disease (AD). Cerebral metabolism is limited to glucose under most conditions, and diminished cerebral glucose metabolism is a characteristic feature of AD. Another substrate available for cerebral metabolism is ketone bodies. Ketone bodies (KB) are normally derived from fat stores under conditions of low glucose availability as an alternative energy substrate to glucose. KB can also be produced by oral administration of CT. Prior studies suggest that the alternative energy source of CT may improve cognitive function due to mild to moderate AD, by circumventing the diminished glucose metabolism. The effect of CT was analyzed in a single-case of mild AD with cognitive alterations in an open label study. Study outcomes included the Montreal cognitive assessment (MoCA), mini mental state exam (MMSE), and 18-fluorodeoxyglucose (18F) positron emission tomography (FDG PET) scans. After 109 days of CT, MoCA scores changed from a baseline value of 24-28, and MMSE scores changed from 23 to 28. No changes were observed on FDG PET scans. The results suggest that, in a case of mild AD, CT may have affected cognitive function, assessed by means of MMSE and MoCA, although glucose uptake and metabolism remained unchanged.

  6. Maintained cerebral metabolic ratio during exercise in patients with beta-adrenergic blockade

    DEFF Research Database (Denmark)

    Gam, Christiane M B; Rasmussen, Peter; Secher, Niels H

    2009-01-01

    BACKGROUND: Decreased cerebral metabolic ratio (CMR) [molar uptake of O(2) versus molar uptake of (glucose + (1/2) lactate)] during exercise is attenuated by intravenous administration of the non-selective beta-adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic...... patients in oral treatment with propranolol are able to mobilize brain non-oxidative carbohydrate metabolism. METHODS: Incremental cycle ergometry to exhaustion (86 +/- 4.2 W; mean +/- SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde...... and during exercise, respectively. During exercise the glucose a-v diff of 0.46 +/- 0.06 mM remained at a level similar to rest (0.54 +/- 0.03 mM) and at exhaustion the CMR was not significantly changed (5.8 +/- 1.1 versus 6.0 +/- 0.6). In controls, CMR decreased from 5.6 +/- 0.9 at rest to 3.4 +/- 0.7 (P

  7. Depressed cerebral oxygen metabolism in patients with chronic renal failure. A positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Hirakata, Hideki; Kanai, Hidetoshi; Nakane, Hiroshi; Fujii, Ken-ichiro; Hirakata, Eriko; Ibayashi, Setsuro; Kuwabara, Yasuo; Deenitchna, S.S.; Fujishima, Masatoshi [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences

    2001-07-01

    In order to elucidate brain oxygen metabolism in uremic patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF) and oxygen metabolism (rCMRO{sub 2}) were measured by positron emission tomography (PET) in both 10 hemodialysis patients (HD: male [m]/female [f]=2/8, age of 49{+-}3 [SEM] years old, HD duration of 113{+-}26 months) and 13 pre-dialysis renal failure patients (CRF: m/f=10/3, age of 61{+-}2 years old, serum creatinine (SCr) of 6.3{+-}1.0 mg/dl). Data were compared with 20 non-uremic subjects (Control: m/f=7/13, age of 62{+-}2 years old, SCr of 0.9{+-}0.1 mg/dl). They had no neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. The age of HD was significantly younger than the other groups (p<0.02) and the hemoglobin (Hb) levels in both HD (10.5{+-}0.5 g/dl) and CRF (9.8{+-}0.9) were significantly lower than that in Control (13.3{+-}0.3) (p<0.02). In the hemisphere, rCMRO{sub 2} in both HD (1.82{+-}0.10 ml/min/100 g) and CRF (1.95{+-}0.09) showed significantly lower values as compared to Control (2.23{+-}0.05) (p<0.01, respectively). Hemispheric rCBF in HD (35.6{+-}2.1 ml/100 g/min) and in CRF (36.1{+-}2.1) were not different from that in Control (31.8{+-}1.4). Hemispheric rOEF in CRF (45.7{+-}1.6%) was significantly higher than that in Control (40.5{+-}1.2%) (p<0.02), but that in HD (43.7{+-}1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially in the cerebral cortices, but not in the cerebellum. All PET parameters in the frontal cortices tended to show the lowest value in renal failure patients. For all HD patients, rCBF in both the frontal cortex and the white matter correlated inversely with HD duration (frontal cortex: r=-0.649, p<0.05; white matter: r=-0.706, p<0.02). Based on these data, it is concluded that brain oxygen metabolism is depressed in renal failure

  8. Cerebral haemodynamic response or excitability is not affected by sildenafil

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Hansen, Adam E; Larsson, Henrik B W

    2009-01-01

    Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70...

  9. Rapid Disruption of Axon–Glial Integrity in Response to Mild Cerebral Hypoperfusion

    OpenAIRE

    Reimer, Michell M.; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Philip R Holland; Smith, Jessica; Gliddon, Catherine; Wood, Emma R.; Herzyk, Pawel; Brophy, Peter J.; Mcculloch, James; Horsburgh, Karen

    2011-01-01

    Myelinated axons have a distinct protein architecture which is essential for action potential propagation, neuronal communication and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, is suggested to contribute to age-related cognitive decline. We sought to determine whether there are selective and early alterations in the protein architecture of myelinated axons in response to cerebral hypoperfusion. Using a mouse model of hypoperfusion we as...

  10. Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

    OpenAIRE

    Hanafy, Khalid A.; Stuart, R. Morgan; Fernandez, Luis; Schmidt, J. Michael; Claassen, Jan; Lee, Kiwon; Connolly, E. Sander; Mayer, Stephan A.; Badjatia, Neeraj

    2009-01-01

    Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of ...

  11. Luminance contrast of a visual stimulus modulates the BOLD response more than the cerebral blood flow response in the human brain.

    Science.gov (United States)

    Liang, Christine L; Ances, Beau M; Perthen, Joanna E; Moradi, Farshad; Liau, Joy; Buracas, Giedrius T; Hopkins, Susan R; Buxton, Richard B

    2013-01-01

    The blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI) depends on the evoked changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) in response to changes in neural activity. This response is strongly modulated by the CBF/CMRO(2) coupling relationship with activation, defined as n, the ratio of the fractional changes. The reliability of the BOLD signal as a quantitative reflection of underlying physiological changes depends on the stability of n in response to different stimuli. The effect of visual stimulus contrast on this coupling ratio was tested in 9 healthy human subjects, measuring CBF and BOLD responses to a flickering checkerboard at four visual contrast levels. The theory of the BOLD effect makes a robust prediction-independent of details of the model-that if the CBF/CMRO(2) coupling ratio n remains constant, then the response ratio between the lowest and highest contrast levels should be higher for the BOLD response than the CBF response because of the ceiling effect on the BOLD response. Instead, this response ratio was significantly lower for the BOLD response (BOLD response: 0.23 ± 0.13, mean ± SD; CBF response: 0.42 ± 0.18; p=0.0054). This data is consistent with a reduced dynamic range (strongest/weakest response ratio) of the CMRO(2) response (~1.7-fold) compared to that of the CBF response (~2.4-fold) as luminance contrast increases, corresponding to an increase of n from 1.7 at the lowest contrast level to 2.3 at the highest contrast level. The implication of these results for fMRI studies is that the magnitude of the BOLD response does not accurately reflect the magnitude of underlying physiological processes. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Directory of Open Access Journals (Sweden)

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  13. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

    DEFF Research Database (Denmark)

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki

    2015-01-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled...... to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples...... were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined...

  14. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...... a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...... evaluable and regional cerebral metabolic rate for glucose (rCMRglc) was estimated in nontumoral brain regions in 12 patients treated with surgery alone and 9 patients treated with both surgery and CRT. Furthermore 10 normal controls matched for age at examination were included. Patients treated with both...

  15. Cerebral Oximetry in Ugandan Children With Severe Anemia: Clinical Categories and Response to Transfusion.

    Science.gov (United States)

    Dhabangi, Aggrey; Ainomugisha, Brenda; Cserti-Gazdewich, Christine; Ddungu, Henry; Kyeyune, Dorothy; Musisi, Ezra; Opoka, Robert; Stowell, Christopher P; Dzik, Walter H

    2016-10-01

    Severe anemia, defined as a hemoglobin level of less than 5.0 g/dL, affects millions of children worldwide. The brain has a high basal demand for oxygen and is especially vulnerable to hypoxemia. Previous studies have documented neurocognitive impairment in children with severe anemia. Data on cerebral tissue oxygenation in children with severe anemia and their response to blood transfusion are limited. To measure hemoglobin saturation in cerebral tissue (cerebral tissue oxygen saturation [tSo2]) before, during, and after blood transfusion in a cohort of children presenting to hospital with severe anemia. This was a prospective, observational cohort study conducted from February 2013 through May 2015 and analyzed in July 2015 at a university hospital pediatric acute care facility in Kampala, Uganda, of 128 children, ages 6 to 60 months who were enrolled in a larger clinical trial, with a presenting hemoglobin level of less than 5.0 g/dL and a blood lactate level greater than 5mM. Most children had either malaria or sickle cell disease. Red blood cell (RBC) transfusion given as 10 mL/kg over 120 minutes. Clinical and laboratory characteristics of children with pretransfusion cerebral tSo2 levels less than 65%, 65% to 75%, and greater than 75%. Change in cerebral tSo2 as a result of transfusion. Of 128 children included in the study, oximetry results in 8 cases were excluded owing to motion artifacts; thus, 120 were included in this analysis. Cerebral tSo2 values prior to transfusion ranged from 34% to 87% (median, 72%; interquartile range [IQR], 65%-76%). Eighty-one children (67%) demonstrated an initial cerebral tSo2 level (≤75%) corresponding to an oxygen extraction ratio greater than 0.36. Patients with sickle cell disease (n = 17) and malaria (n = 15) contributed in nearly equal numbers to the subgroup with an initial cerebral tSo2 (children failed to achieve a tSo2 level greater than 75%. Severe anemia in children is frequently associated with low

  16. [Effect of hyperventilation on cerebral blood flow and metabolism in man; continuous monitoring of arterio-cerebral venous glucose differences (author's transl)].

    Science.gov (United States)

    Gottstein, U; Zahn, U; Held, K; Gabriel, F H; Textor, T; Berghoff, W

    1976-04-15

    CBF decreases when arterial PCO2 is lowered by physiological, pathological or therapeutically induced hyperventilation. This is accompanied by an undelayed compensatory increase of oxygen-av-differences. Continuous monitoring of enzymatically determined glucose-av-differences of the brain during hyperventilation has for the first time shown that there is an undelayed fall of the cerebral venous glucose content, too. This indicates that the brain cells extract an augmented amount of glucose per ml blood during decreased CBF. Therefore glucose metabolism of the brain is not impaired during non-critical CBF reduction. However, when arterial PCO2 falls below 25 mmHg a detrimental effect on CBF and cerebral metabolism has to be expected. CBF will then decrease below the critical threshold for an undisturbed oxygen supply, and the respiratory alcalosis will lead to a disturbed oxygen delivery due to the Bohr-effect. As a consequence both of these factors will reduce the energy-yielding oxydative glycolysis and augment the little energy producing anaerobic glycolysis with a concomitant increase of lactate formation, resulting in a tissue and spinal fluid lactate acidosis. From our results it is therefore concluded that induced hyperventilation should be avoided, and that central hyperventilation in diseased states has to be considered as an additional threat to the brain.

  17. The Role of Exercise – Rehabilitation on Energy Cost and Metabolic Efficiency in Dipelegic Spastic Cerebral Palsy Children

    Directory of Open Access Journals (Sweden)

    M. Izadi

    2005-07-01

    Full Text Available Introduction & Objective: The aim of this study was to compare the resting energy expenditure and metabolic efficiency before and after of aerobic exercise in spastic cerebral palsy children (mean age of 11 years and also to compare with those of normal children. Materials & Methods : Fifteen dipelegia spastic cerebral palsy children (experimental group participated in exercise–rehabilitation program by voluntarily and the peers eighteen able body children(control group were selected randomly. The experimental group(cp performed rehabilitation program for 3 months,3 session in week with work intensity(%HRR=462.5equal to144bpm of heart rate. The values were measured on tantory cycle ergometer according to Macmaster protocol.Results: Rest and exercise heart rate and exercise intensity(%HRR in patients decreased after rehabilitation program(P<0.05. The resting energy expenditure was similar in cp and normal groups. The rate of oxygen cost of patients decreased in post test(P<0.05 that showed increasing in metabolic efficiency.Conclusion: cerebral palsy children have greater exercise energy cost and lower cardiovascular fitness than normal children and exercise–rehabilitation leads to enhance of metabolic efficiency in this patients that is remarkable from clinical perception.

  18. Visual and SPM analysis of regional cerebral glucose metabolism in adult patients with neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; An, Young Sil; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University, School of Medicine, Suwon (Korea, Republic of)

    2005-07-01

    We evaluated the regional cerebral glucose metabolism in adult patients with neurofibromatosis (NF) using visual and SPM analysis, and compared with MRI findings. A total of 11 adult patients with NF type I were prospectively included in the study. All patients underwent F-18 FDG PET and brain MRI within 2 month of each other. All hypometabolic areas on PET were determined visually by 2 nuclear medicine physician and compared with MRI findings. SPM analysis was done using 42 normal controls with p = 0.005. Seven of 11 PET images showed 10 hypometabolic areas and 4 of 11 MRIs showed 6 areas of signal change brain parenchyma. Hypometabolic areas were bilateral thalamus (n=5), left temporal cortex (n=4) and dentate nucleus (n=1). In only 2 lesions (thalamus and dentate nucleus), hypometabolic foci were consistently related to signal change on MRI. SPM analysis revealed significantly decreased area in bilateral thalamus and left temporal cortex. F-18 FDG PET revealed significant hypometabolism in bilateral thalamus and left temporal cortex in adult patients with NF, and it might be helpful in understanding developmental abnormality of NF.

  19. MicroRNA responses to focal cerebral ischemia in male and female mouse brain

    Directory of Open Access Journals (Sweden)

    Theresa Ann Lusardi

    2014-02-01

    Full Text Available Stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage resulting from an ischemic event compared to females. Previous studies revealed that microRNA (miRNA expression is regulated by cerebral ischemia in males; however, no studies to date have examined the effect of ischemia on miRNA responses in females. Thus, we examined miRNA responses in male and female brain in response to cerebral ischemia using miRNA arrays. These studies revealed that in male and female brains, ischemia leads to both a universal miRNA response as well as a sexually distinct response to challenge. Target prediction analysis of the miRNAs increased in male or female ischemic brain reveal sex-specific differences in gene targets and protein pathways. These data support that the mechanisms underlying sexually dimorphic responses to cerebral ischemia includes distinct changes in miRNAs in male and female brain, in addition to a miRNA signature response to ischemia that is common to both.

  20. Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

    Directory of Open Access Journals (Sweden)

    Yakhya Dieye

    2016-05-01

    Full Text Available Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

  1. Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression.

    Science.gov (United States)

    Nofzinger, Eric A; Buysse, Daniel J; Germain, Anne; Price, Julie C; Meltzer, Carolyn C; Miewald, Jean M; Kupfer, David J

    2005-04-01

    Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. General clinical research center. The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.

  2. Quantifying the cerebral metabolic rate of oxygen by combining diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy.

    Science.gov (United States)

    Verdecchia, Kyle; Diop, Mamadou; Lee, Ting-Yim; St Lawrence, Keith

    2013-02-01

    Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO2) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO2 could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO2) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO2 was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO2 measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO2 measurements. Bland-Altman analysis showed a mean CMRO2 difference of 0.0268 ± 0.8340 mLO2/100 g/min between the two techniques over a range from 0.3 to 4 mL O2/100 g/min.

  3. Extracellular adenosine mediates a systemic metabolic switch during immune response

    National Research Council Canada - National Science Library

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system...

  4. Cerebral metabolic rate of oxygen (CMRO2 ) mapping with hyperventilation challenge using quantitative susceptibility mapping (QSM).

    Science.gov (United States)

    Zhang, Jingwei; Zhou, Dong; Nguyen, Thanh D; Spincemaille, Pascal; Gupta, Ajay; Wang, Yi

    2017-05-01

    Our objective was to demonstrate the feasibility of using hyperventilation as an efficient vasoconstrictive challenge and prior knowledge as denoising constraints for cerebral metabolic rate of oxygen (CMRO2 ) mapping based upon quantitative susceptibility mapping (QSM). Three-dimensional (3D) multi-echo gradient echo and arterial spin labeling imaging were performed to calculate QSM and perfusion maps before and after a hyperventilation challenge in 11 healthy subjects. For comparison, this was repeated using a caffeine challenge. Whole-brain CMRO2 and oxygen extraction fraction (OEF) maps were computed using constrained optimization. Hyperventilation scans were repeated to measure reproducibility. Regional agreement of CMRO2 and OEF maps was analyzed within the cortical gray matter (CGM) using t-test and Bland-Altman plots. Hyperventilation challenge eliminates the 30-min waiting time needed for caffeine to exert its vasoconstrictive effects. Mean CMRO2 (in µmol/100g/min) obtained in CGM using the caffeine and repeated hyperventilation scans were 149 ± 16, 153 ± 19, and 150 ± 20, respectively. This corresponded to an OEF of 33.6 ± 3.4%, 32.3 ± 3.2%, and 34.1 ± 3.8% at baseline state and 39.8 ± 4.8%, 43.6 ± 6.2%, and 42.8 ± 6.8% at challenged state, respectively. Hyperventilation scans produced a good agreement of CMRO2 and OEF values. Hyperventilation is a feasible, reproducible, and efficient vasoconstrictive challenge for QSM-based quantitative CMRO2 mapping. Magn Reson Med 77:1762-1773, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  5. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

    Directory of Open Access Journals (Sweden)

    Farzaneh A Sorond

    2008-04-01

    Full Text Available Farzaneh A Sorond1,2, Lewis A Lipsitz2,4, Norman K Hollenberg3,5, Naomi DL Fisher31Department of Neurology, Stroke Division; 2Institute for Aging Research, Hebrew SeniorLife, Boston, MA; 3Department of Medicine, Endocrine-Hypertension Division; 4Department of Medicine, Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Department of Radiology, Brigham and Women’s Hospital, Boston, MABackground and Purpose: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC consumption on cerebral blood flow in older healthy volunteers.Methods: We used transcranial Doppler (TCD ultrasound to measure mean blood flow velocity (MFV in the middle cerebral artery (MCA in thirty-four healthy elderly volunteers (72 ± 6 years in response to the regular intake of FRC or flavanol-poor cocoa (FPC.Results: In response to two weeks of FRC intake, MFV increased by 8% ± 4% at one week (p = 0.01 and 10% ± 4% (p = 0.04 at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05.Conclusions: In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol’s consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.Keywords: cerebral blood flow, flavanol, cocoa, transcranial Doppler ultrasound

  6. Maximal aerobic and anaerobic exercise responses in children with cerebral palsy.

    NARCIS (Netherlands)

    Balemans, A.C.J.; van Wely, L.; de Heer, S.J.; van den Brink, J.; de Koning, J.J.; Becher, J.G.; Dallmeijer, A.J.

    2013-01-01

    PURPOSE: The objective of this study is to compare the maximal aerobic and anaerobic exercise responses of children with cerebral palsy (CP) by level of motor impairment and in comparison with those of typically developing children (TD). METHODS: Seventy children with CP, with varying levels of

  7. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  8. Monitoring of cerebral blood flow and metabolism bedside in patients with subarachnoid hemorrhage - A Xenon-CT and microdialysis study.

    Directory of Open Access Journals (Sweden)

    Elham eRostami

    2014-06-01

    Full Text Available Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH. Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as Delayed cerebral ischemia (DCI. Early detection and management of reversible ischemia is of critical importance in patients with SAH.Xenon computerized tomography (Xenon-CT using a bedside CT scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF bedside in the neurointensive care (NIC setting and intracerebral microdialysis is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here we present results on nine SAH patients with both microdialysis monitoring and bedside Xenon-CT measurements.CBF measurements were performed within the first 72h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100g/min whereas one had 53 ml/100g/min. The 3 patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100g/min. High Lactate/Pyruvate ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had Lactate/Pyruvate ratio ≥ 25 and four of these patients had CBF ≤ 22 ml/100g/min.These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied by metabolic disturbances determined by the microdialysis. Most importantly, pathological findings on the Xenon-CT and microdialysis could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and microdialysis was found to be useful and feasible. Further studies are needed to evaluate if delayed cerebral ischemia can be detected before any other signs of DCI to prevent progress to infarction.

  9. Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Hilda Ahnstedt

    Full Text Available BACKGROUND AND PURPOSE: Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation. EXPERIMENTAL APPROACH: Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B, angiotensin II type 1 (AT1 and endothelin-1 type A and B (ETA and ETB receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression. KEY RESULTS: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture. CONCLUSIONS AND IMPLICATIONS: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.

  10. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans.

    Science.gov (United States)

    Sorond, Farzaneh A; Lipsitz, Lewis A; Hollenberg, Norman K; Fisher, Naomi D Ll

    2008-04-01

    Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. We used transcranial Doppler (TCD) ultrasound to measure mean blood flow velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly volunteers (72 +/- 6 years) in response to the regular intake of FRC or flavanol-poor cocoa (FPC). In response to two weeks of FRC intake, MFV increased by 8% +/- 4% at one week (p = 0.01) and 10% +/- 4% (p = 0.04) at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p flavanol's consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.

  11. Autonomic cerebral vascular response to sildenafil in diabetic patient

    Directory of Open Access Journals (Sweden)

    Al-Amran Fadhil G

    2012-01-01

    Full Text Available Abstract Background Erectile dysfunction is a common problem in type 2 diabetic patients who are at higher risk of cerebrovascular events, and it's recorded with sildenafil, a drug which is primarily used for erectile dysfunction. Objectives We tested the hypothesis whether or not sildenafil modulates cerebrovascular reactivity (CVR in patients with type 2 diabetes mellitus. Methods A total of 35 male participants were enrolled; eighteen with type 2 diabetes mellitus matched with seventeen normal individuals. Transcranial Doppler Ultrasonographic examination (TCD was performed for all participants to insonate the middle cerebral artery (MCA through a trans-temporal window. CVR was assessed by using breath holding (BH-hyperventilation (HV test, before and after oral 50 mg sildenafil; recordings were analyzed by using SPSS program version 12. Results In normal individuals, sildenafil did not result in statistically significant change in breath holding index (BHI from 0.91 ± 0.11 to 0.81 ± 0.09 and full range of vasodilatation (FVD from (59.4% ± 6.3% to (53.7% ± 4.9%. In diabetic patients, giving sildenafil resulted in significant increase in BHI (from 0.74 ± 0.14 to 1.03 ± 0.14 and FVD (from 60.2% ± 4.96% to 74% ± 4.8%, (p Conclusion Sildenafil significantly improves CVR in type 2 diabetic patients but not in normal subjects.

  12. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock.

    Science.gov (United States)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M; Duggan, Michael; Sillesen, Martin; Deperalta, Danielle; Jepsen, Cecilie H; Lu, Jennifer; Li, Yongqing; deMoya, Marc A; Alam, Hasan B

    2013-08-01

    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this effect was owing to metabolic modulation. Yorkshire swine (n = 9) underwent a protocol of computer-controlled TBI and 40% hemorrhage and were resuscitated randomly with either fresh frozen plasma equal to the volume of shed blood (FFP; n = 4) or VPA (300 mg/kg) and FFP (FFP+VPA; n = 5). Hemodynamics, brain oxygenation, and blood glucose were monitored continuously for 6 hours after resuscitation. Cerebral microdialysis was used to measure glucose, lactate, pyruvate, glutamate, and glycerol levels at baseline, 1 and 2 hours post-shock, post-resuscitation (PR), and at 2, 4, and 6 hours PR. Brain samples from the injured side were then separated into mitochondrial and cytosolic fractions, and activity of pyruvate dehydrogenase complex (PDH) was measured using a dipstick assay kit. At baseline, there was no difference in brain lactate, pyruvate, glycerol, and glutamate concentrations between the groups. At all time points, there were no differences between the groups in brain oxygenation, cerebral perfusion pressure, or blood and brain glucose concentrations. After VPA infusion (PR time point), however, there was sustained decrease in lactate (0.91 ± 0.47 vs 2.54 ± 0.59 mmol/L; P glucose utilization for ATP production. There was also a decrease in concentrations of glutamate (6.64 ± 3.68 vs 42.25 ± 27.07 mmol/L; P = .02) and glycerol (19.20 ± 6.76 vs 69.75 ± 30.07 mmol/L; P = .01), in the FFP+VPA group, signifying lesser degree of excitotoxicity and brain damage, respectively. Brain PDH activity was greater in the mitochondrial fractions (5,984 ± 504 adjusted volume intensity [INT] × mm(2) vs 4,332 ± 1,055 INT × mm(2); P = .04) and lower in cytosolic fractions in the FFP

  13. Changes of metabolism and functional connectivity in late-onset deafness: Evidence from cerebral 18F-FDG-PET.

    Science.gov (United States)

    Verger, Antoine; Roman, Stéphane; Chaudat, Rose-May; Felician, Olivier; Ceccaldi, Mathieu; Didic, Mira; Guedj, Eric

    2017-09-01

    Hearing loss is known to impact brain function. The aim of this study was to characterize cerebral metabolic Positron Emission Tomography (PET) changes in elderly patients fulfilling criteria for cochlear implant and investigate the impact of hearing loss on functional connectivity. Statistical Parametric Mapping-T-scores-maps comparisons of 18F-FDG-PET of 27 elderly patients fulfilling criteria for cochlear implant for hearing loss (best-aided speech intelligibility lower or equal to 50%) and 27 matched healthy subjects (p < 0.005, corrected for volume extent) were performed. Metabolic connectivity was evaluated through interregional correlation analysis. Patients were found to have decreased metabolism within the right associative auditory cortex, while increased metabolism was found in prefrontal areas, pre- and post-central areas, the cingulum and the left inferior parietal gyrus. The right associative auditory cortex was integrated into a network of increased metabolic connectivity that included pre- and post-central areas, the cingulum, the right inferior parietal gyrus, as well as the striatum on both sides. Metabolic values of the right associative auditory cortex and left inferior parietal gyrus were positively correlated with performance on neuropsychological test scores. These findings provide further insight into the reorganization of the connectome through sensory loss and compensatory mechanisms in elderly patients with severe hearing loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

    Energy Technology Data Exchange (ETDEWEB)

    Hassel, B.

    1995-11-01

    The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.

  15. The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats.

    Science.gov (United States)

    Prins, Mayumi L; Hovda, David A

    2009-07-01

    Previous studies from our laboratory have shown the neuroprotective potential of ketones after TBI in the juvenile brain. It is our premise that acutely after TBI, glucose may not be the optimum fuel and decreasing metabolism of glucose in the presence of an alternative substrate will improve cellular metabolism and recovery. The current study addresses whether TBI will induce age-related differences in the cerebral metabolic rates for glucose (CMRglc) after cortical controlled impact (CCI) and whether ketone metabolism will further decrease CMRglc after injury. Postnatal day 35 (PND35; n = 48) and PND70 (n = 42) rats were given either sham or CCI injury and placed on either a standard or a ketogenic (KG) diet. CMRglc studies using (14)C-2 deoxy-D-glucose autoradiography were conducted on days 1, 3, or 7 post-injury. PND35 and PND70 standard-fed CCI-injured rats exhibited no significant neocortical differences in CMRglc magnitude or time course compared to controls. Measurement of contusion volume also indicated no age differences in response to TBI. However, PND35 subcortical structures showed earlier metabolic recovery compared to controls than PND70. Ketosis induced by the KG diet was shown to affect CMRglc in an age-dependent manner after TBI. The presence of ketones after injury further reduced CMRglc in PND35 and normalized CMRglc in PND70 rats at 7 days bilaterally after injury. The changes in CMRglc seen in PND35 TBI rats on the KG diet were associated with decreased contusion volume. These results suggest that conditions of reduced glucose utilization and increased alternative substrate metabolism may be preferable acutely after TBI in the younger rat.

  16. Non-selective beta-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans

    DEFF Research Database (Denmark)

    Larsen, T.S.; Rasmussen, P.; Overgaard, M.

    2008-01-01

    Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O(2)/(glucose + (1/2)lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 +/- 4.2 mm (mean +/- s...... of a non-selective beta-adrenergic (beta(1) + beta(2)) receptor antagonist (propranolol) reduced heart rate (69 +/- 8 to 58 +/- 6 beats min(-1)) and exercise capacity (239 +/- 42 to 209 +/- 31 W; P exercise with propranolol, the increase in a......-v lactate difference (to 0.5 +/- 0.5 mm; P exercise with administration of the beta(1...

  17. Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats

    DEFF Research Database (Denmark)

    Ma, Xiaodong; Bay-Hansen, Rikke; Hauerberg, John

    2006-01-01

    In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 levels...... after experimental SAH in rats (injection of 0.07 mL of autologous blood into the cisterna magna). Four groups of Sprague-Dawley male rats were studied at predetermined PaCO2 levels: group A: normocapnia (5.01-5.66 kPa [38.0-42.0 mm Hg]); group B: slight hyperventilation (4.34-5.00 kPa [32.5-37.5 mm Hg......]); group C: moderate hyperventilation (3.67-4.33 kPa [27.5-32.4 mm Hg]); group D: profound hyperventilation (3.00-3.66 kPa [22.5-27.4 mm Hg]). Each of the four groups included eight rats with SAH and eight sham-operated controls. CBF was determined by the intracarotid Xe method; CMRo2, CMRglc, and CMRlac...

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    Science.gov (United States)

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . Copyright © 2015 the American Physiological Society.

  19. Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression.

    Science.gov (United States)

    Little, John T; Ketter, Terence A; Kimbrell, Tim A; Dunn, Robert T; Benson, Brenda E; Willis, Mark W; Luckenbaugh, David A; Post, Robert M

    2005-02-01

    Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy. Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans. For each medication PET data from patients compared with control subjects was analyzed as a function of treatment response (defined as moderate to marked improvement on the Clinical Global Impression Scale). Treatment response rates were similar for buproprion (32%) and venlafaxine (33%). Compared with control subjects, responders but not nonresponders, to both drugs demonstrated frontal and left temporal hypometabolism. Selectively, compared with control subjects bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders (n = 7) showed bilateral temporal and basal ganglia hypometabolism. These data suggest that pretreatment frontal and left temporal hypometabolism in never-hospitalized depressed outpatients compared with control subjects is linked to positive antidepressant response and that additional alterations in regional metabolism may be linked to differential responsivity to bupropion and venlafaxine monotherapy.

  20. Different cerebral metabolic features in dementia with lewy bodies with/without visual hallucination

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bom Sahn; Kim, Yu Kyeong; Yang, Young Soon; Park, Eun Kyung; Cho, Sang Soo; Kim, Sang Yun; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Reduction of glucose metabolism in the occipital cortex is well known in dementia with Lewy Bodies (DLB). The aim of this study was to evaluate the different nature of FDG PET in DLB patients who had visual hallucination or not. Thirteen patients (729 yrs, m:f=6:7) with DLB participated. DLB patient were classified into two groups according to the presence of visual hallucination; seven DLB patients with visual hallucination and 6 patients without visual hallucination. No differences between patient with and without visual hallucination was found in their cognitive function measured by mini mental status exam (MMSE) and clinical dementia rating (CDR) scale. Age and gender matched 30 healthy subjects (age; 715 yrs, m: f = 13:17) served as controls for comparison purpose. Regional metabolic differences on FDG PET among the groups were tested using SPM. In DLB patients groups regardless of visual hallucination, significant regional hypometabolism were observed in the bilateral occipital cortices as well as bilateral parietotemporal and frontal association cortices when compared with healthy controls, as expected. In DLB patients with visual hallucination compared to patients without hallucination, regional hypometabolism over primary and secondary visual cortex (BA17, BA18) was more significant. Moreover, lower regional metabolism in the paracentral area (BA 6) and cerebellar vermis was also observed in DLB with visual hallucination than without hallucination. Profound hypometabolism in the visual cortex may be a feature in DLB patients with visual hallucination. Also, relative hypometabolism in the paracentral area and cerebellum could be neurobiological characteristics related with abnormal cognitive and motor process response to hallucination.

  1. Effect of preceding exercise on cerebral and splanchnic vascular responses to mental task

    Directory of Open Access Journals (Sweden)

    Someya Nami

    2012-06-01

    Full Text Available Abstract Background To investigate the effect of preceding acute exercise on the peripheral vascular response to a mental task, we measured splanchnic and cerebral blood flow responses to performing a mental task after exercise and resting. Methods In the exercise trial, 11 males exercised for 30 min on a cycle ergometer with a workload set at 70% of the age-predicted maximal heart rate for each individual. After a 15-min recovery period, the subjects rested for 5 min for pre-task baseline measurement and then performed mental arithmetic for 5 min followed by 5 min of post-task measurement. In the resting trial, they rested for 45 min and pre-task baseline data was obtained for 5 min. Then mental arithmetic was performed for 5 min followed by post-task measurement. We measured the mean blood velocity in the middle cerebral artery and superior mesenteric artery and the mean arterial pressure. Results Mean arterial pressure and mean blood velocity in the middle cerebral artery were significantly higher than the baseline during mental arithmetic in both exercise and resting trials. Mean blood velocity in the middle cerebral artery during mental arithmetic was greater in the control trial than the exercise trial. Mean blood velocity in the superior mesenteric artery showed no significant change during mental arithmetic from baseline in both trials. Conclusion These results suggest that acute exercise can moderate the increase in cerebral blood flow induced by a mental task.

  2. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-13C]Glucose and [1,2-13C]Acetate as Substrates.

    Science.gov (United States)

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B; Andersen, Jens V; Aldana, Blanca I; Nissen, Jakob D; Schousboe, Arne; Waagepetersen, Helle S

    2017-03-01

    Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design. Cerebral cortical and hippocampal slices prepared from 16 to 18-week-old mice were incubated for 15-90 min with unlabeled glucose in combination with [U-13C]glucose or [1,2-13C]acetate. Our newly developed incubation apparatus allows accurate control of temperature and is designed to avoid evaporation of the incubation medium. Subsequent to incubation, slices were extracted and extracts analyzed for 13C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation media. Based on the measured 13C-labeling (%), total amino acid contents and relative activity of metabolic enzymes/pathways, we conclude that the slice preparations in the current incubation apparatus exhibited a high degree of metabolic integrity. Comparison of 13C-labeling observed with [U-13C]glucose in slices from cerebral cortex and hippocampus revealed no significant regional differences regarding glycolytic or total TCA cycle activities. On the contrary, results from the incubations with [1,2-13C]acetate suggest a higher capacity of the astrocytic TCA cycle in hippocampus compared to cerebral cortex. Finally, we propose a new approach for assessing compartmentation of metabolite pools between astrocytes and neurons using 13C-labeling (%) data obtained from mass

  3. Surgical manipulation compromises leukocyte mobilisation responses and inflammation after experimental cerebral ischaemia in mice

    Directory of Open Access Journals (Sweden)

    Adam eDenes

    2014-01-01

    Full Text Available Acute brain injury results in peripheral inflammatory changes, although the impact of these processes on neuronal death and neuroinflammation is currently unclear. To facilitate the translation of experimental studies to clinical benefit, it is vital to characterize the mechanisms by which acute brain injury induces peripheral inflammatory changes, and how these are affected by surgical manipulation in experimental models. Here we show that in mice, even mild surgical manipulation of extracranial tissues induced marked granulocyte mobilisation (300% and systemic induction of cytokines. However, intracranial changes induced by craniotomy, or subsequent induction of focal cerebral ischaemia were required to induce egress of CXCR2-positive granulocytes from the bone marrow. CXCR2 blockade resulted in reduced mobilisation of granulocytes from the bone marrow, caused an unexpected increase in circulating granulocytes, but failed to effect brain injury induced by cerebral ischaemia. We also demonstrate that isoflurane anaesthesia interferes with circulating leukocyte responses, which could contribute to the reported vascular and neuroprotective effects of isoflurane. In addition, no immunosuppression develops in the bone marrow after experimental stroke. Thus, experimental models of cerebral ischaemia are compromised by surgery and anaesthesia in proportion to the severity of surgical stress and overall tissue injury. Understanding the inherent confounding effects of surgical manipulation and development of new models of cerebral ischaemia with minimal surgical intervention could facilitate better understanding of interactions between inflammation and brain injury.

  4. Cerebral microvascular network geometry changes in response to functional stimulation.

    Science.gov (United States)

    Lindvere, Liis; Janik, Rafal; Dorr, Adrienne; Chartash, David; Sahota, Bhupinder; Sled, John G; Stefanovic, Bojana

    2013-05-01

    The cortical microvessels are organized in an intricate, hierarchical, three-dimensional network. Superimposed on this anatomical complexity is the highly complicated signaling that drives the focal blood flow adjustments following a rise in the activity of surrounding neurons. The microvascular response to neuronal activation remains incompletely understood. We developed a custom two photon fluorescence microscopy acquisition and analysis to obtain 3D maps of neuronal activation-induced changes in the geometry of the microvascular network of the primary somatosensory cortex of anesthetized rats. An automated, model-based tracking algorithm was employed to reconstruct the 3D microvascular topology and represent it as a graph. The changes in the geometry of this network were then tracked, over time, in the course of electrical stimulation of the contralateral forepaw. Both dilatory and constrictory responses were observed across the network. Early dilatory and late constrictory responses propagated from deeper to more superficial cortical layers while the response of the vertices that showed initial constriction followed by later dilation spread from cortical surface toward increasing cortical depths. Overall, larger caliber adjustments were observed deeper inside the cortex. This work yields the first characterization of the spatiotemporal pattern of geometric changes on the level of the cortical microvascular network as a whole and provides the basis for bottom-up modeling of the hemodynamically-weighted neuroimaging signals. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Frederiksen, Hans-Jørgen

    2012-01-01

    Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA...

  6. Global Metabolic Responses to Salt Stress in Fifteen Species.

    Directory of Open Access Journals (Sweden)

    Daniel C Sévin

    Full Text Available Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species' taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance.

  7. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  8. Cerebral metabolic changes (F-18-FDG PET) during selective anterior temporal lobe amobarbital test

    NARCIS (Netherlands)

    Khan, N; Hajek, M; Antonini, A; Maguire, P; Muller, S; Valavanis, A; Leenders, KL; Regard, M; Schiess, R; Wieser, HG

    1997-01-01

    Cerebral glucose utilisation using F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) was measured in 4 patients with temporal lobe epilepsy during a selective anterior temporal lobe (TL) amobarbital test (ATLAT) and compared with their baseline values. F-18-FDG was injected

  9. Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hempel, Casper; Sjövall, Fredrik

    2013-01-01

    Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting...

  10. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    Science.gov (United States)

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  11. Typical cerebral metabolic patterns in various types of dementia: an SPM analysis of 18F-FDG PET images

    Directory of Open Access Journals (Sweden)

    Rui-xue CUI

    2014-04-01

    Full Text Available Objective To delineate the cerebral metabolic patterns presented in 18F-FDG PET images in various types of dementia with SPM analysis.  Methods Patients who underwent 18F-FDG PET scanning with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria were studied. Clinical follow-up enabled appropriate patient inclusion. A total of 62 patients were included, of which 20 patients were diagnosed as Alzheimer's disease (AD, 20 frontotemporal dementia (FTD, 10 dementia with Lewy body (DLB, 7 progressive supranuclear palsy (PSP, 3 primary progressive aphasia (PPA, 1 corticobasal ganglionic degeneration (CBD, 1 multiple system atrophy (MSA. 18F-FDG PET images of each group were analyzed and compared to 20 healthy controls using SPM5. Results Disease-specific patterns of relatively decreased metabolic activity were found in AD (bilateral parietotemporal regions and frontal regions sparing sensorimotor cortex, FTD (asymmetric frontotemporal regions, DLB (occipital lobe, visual cortex and bilateral superior temporal gyrus, PSP (bilateral dorsolateral prefrontal cortex, anterolateral temporal regions, caudate nucleus and mesencephalon, PPA (Broca's area in left frontal lobe, left temporal cortex excepting posterior superior temporal gyrus, CBD (asymmetricly involved cortical regions, prodominately on right side, around bilateral central sulcus and right basal ganglia, MSA (bilateral cerebellum dorsolateral cortex and left putamen, and right medial temporal cortex.  Conclusions Specific dementia related cerebral metabolic patterns in 18F-FDG PET might assist in early differential diagnosis of neurodegenerative diseases. doi: 10.3969/j.issn.1672-6731.2014.04.008

  12. Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children

    Energy Technology Data Exchange (ETDEWEB)

    Kern, F.H.; Ungerleider, R.M.; Quill, T.J.; Baldwin, B.; White, W.D.; Reves, J.G.; Greeley, W.J. (Duke Univ. Medical Center, Durham, NC (USA))

    1991-04-01

    We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbon dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.

  13. RELATCH: relative optimality in metabolic networks explains robust metabolic and regulatory responses to perturbations

    OpenAIRE

    Kim, Joonhoon; Reed, Jennifer L

    2012-01-01

    Predicting cellular responses to perturbations is an important task in systems biology. We report a new approach, RELATCH, which uses flux and gene expression data from a reference state to predict metabolic responses in a genetically or environmentally perturbed state. Using the concept of relative optimality, which considers relative flux changes from a reference state, we hypothesize a relative metabolic flux pattern is maintained from one state to another, and that cells adapt to perturba...

  14. Possible stimuli for strength and power adaptation : acute metabolic responses.

    Science.gov (United States)

    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

    The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

  15. Comparing fludeoxyglucose F18-PET assessment of regional cerebral glucose metabolism and [11C]dihydrotetrabenazine-PET in evaluation of early dementia and mild cognitive impairment.

    Science.gov (United States)

    Albin, Roger L; Koeppe, Robert A; Burke, James F; Giordani, Bruno; Kilbourn, Michael R; Gilman, Sid; Frey, Kirk A

    2010-04-01

    To compare assessment of regional cerebral metabolic changes with [(11)C]dihydrotetrabenazine (DTBZ)-positron emission tomography (PET) measurement of regional cerebral blood flow (K(1)) and fludeoxyglucose F18 (FDG)-PET measurement of regional cerebral glucose uptake (CMR(glc)) in a clinically representative sample of subjects with mild dementia and mild cognitive impairment (MCI). [(11)C]Dihydrotetrabenazine-PET K(1) and FDG-PET CMR(glc) measurements were performed. University-based cognitive disorders clinic. Fifty subjects with either mild dementia (Mini-Mental State Examination score > or = 18) or MCI. Their results were compared with those of 80 normal control subjects. The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were compared with standard correlation analysis. The overall patterns of DTBZ-PET K(1) and FDG-PET CMR(glc) deficits were assessed with stereotaxic surface projections (SSPs) of parametric images. The DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were highly correlated, both within and between subjects. The SSP maps of deficits in DTBZ-PET regional K(1) and FDG-PET CMR(glc) measurements were markedly similar. The DTBZ-PET K(1) SSP maps exhibited a mild decrease in sensitivity relative to FDG-PET CMR(glc) maps. Both DTBZ-PET K(1) and FDG-PET CMR(glc) measurements provide comparable information in assessment of regional cerebral metabolic deficits in mild dementia and MCI. Blood flow measures can assess regional cerebral metabolism deficits accurately in mild dementia and MCI. Blood flow assessments of regional cerebral metabolic deficits can be combined with tracer binding results to improve utility of PET imaging in mild dementia and MCI.

  16. Altered regional cerebral glucose metabolism in internet game overusers: a 18F-fluorodeoxyglucose positron emission tomography study.

    Science.gov (United States)

    Park, Hyun Soo; Kim, Sang Hee; Bang, Seong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Eun

    2010-03-01

    Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using 18F-fluorodeoxyglucose positron emission tomography study. Twenty right-handed male participants (9 normal users: 24.7+/-2.4 years of age, 11 overusers: 23.5+/-2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning. Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentral gyrus, and bilateral occipital regions compared to normal users. Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.

  17. Manipulation of the metabolic response in clinical practice

    DEFF Research Database (Denmark)

    Kehlet, H

    2000-01-01

    morbidity. Effective afferent neural blockade with continuous epidural local anesthetic techniques inhibits a major part of the endocrine metabolic response, leading to improved protein economy but without important effects on inflammatory or immunologic responses. In contrast, pain treatment with other...... modalities such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids has only a small inhibitory effect on endocrine metabolic responses. Preoperative high-dose glucocorticoid therapy provides additional pain relief and improves pulmonary function, but it reduces the inflammatory response (acute....... The effect of these techniques to alter endocrine metabolic and inflammatory responses during severe surgical illness has not been established. Neural blockade and minimally invasive surgery have improved outcome following elective surgery, especially when integrated into a multimodal postoperative...

  18. A lumped parameter model of cerebral blood flow control combining cerebral autoregulation and neurovascular coupling.

    Science.gov (United States)

    Spronck, Bart; Martens, Esther G H J; Gommer, Erik D; van de Vosse, Frans N

    2012-11-01

    Cerebral blood flow regulation is based on a variety of different mechanisms, of which the relative regulatory role remains largely unknown. The cerebral regulatory system expresses two regulatory properties: cerebral autoregulation and neurovascular coupling. Since partly the same mechanisms play a role in cerebral autoregulation and neurovascular coupling, this study aimed to develop a physiologically based mathematical model of cerebral blood flow regulation combining these properties. A lumped parameter model of the P2 segment of the posterior cerebral artery and its distal vessels was constructed. Blood flow regulation is exerted at the arteriolar level by vascular smooth muscle and implements myogenic, shear stress based, neurogenic, and metabolic mechanisms. In eight healthy subjects, cerebral autoregulation and neurovascular coupling were challenged by squat-stand maneuvers and visual stimulation using a checkerboard pattern, respectively. Cerebral blood flow velocity was measured using transcranial Doppler, whereas blood pressure was measured by finger volume clamping. In seven subjects, the model proposed fits autoregulation and neurovascular coupling measurement data well. Myogenic regulation is found to dominate the autoregulatory response. Neurogenic regulation, although only implemented as a first-order mechanism, describes neurovascular coupling responses to a great extent. It is concluded that our single, integrated model of cerebral blood flow control may be used to identify the main mechanisms affecting cerebral blood flow regulation in individual subjects.

  19. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia.

    Science.gov (United States)

    Wiegers, Evita C; Becker, Kirsten M; Rooijackers, Hanne M; von Samson-Himmelstjerna, Federico C; Tack, Cees J; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

    2017-06-01

    It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.

  20. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

    DEFF Research Database (Denmark)

    Wone, B W M; Madsen, Per; Donovan, E R

    2015-01-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection...... on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols...... and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR...

  1. Effects of laser acupoint irradiation on energy metabolism of brain tissue of rats with cerebral ischemia-reperfusion

    Science.gov (United States)

    Xiong, Guoxin; Li, Xinzhong

    2017-12-01

    The protective effect and mechanism of low-intensity laser acupoint irradiation on focal cerebral ischemia-reperfusion (CIR) injury in rats were investigated. Male Sprague-Dawley rats were randomly divided into a sham group, a CIR model (model) group, and a model plus laser irradiation (laser) group. The focal CIR model was induced by middle cerebral artery occlusion in all except the rats in the sham group. After modeling, the Baihui, Mingmen, and left Zusanli points of the rats in the laser group were irradiated with 15 mW using a semiconductor laser, and each point was irradiated for 15 min once a day for 7 d. The treatments used in the sham and model groups were the same as in the laser group except that the laser output power was zero. After treatment, the expressions of serum superoxide dismutase (SOD) activity and serum malonaldehyde (MDA) content, the expression of growth-associated protein (GAP-43), the activities of succinic dehydrogenase and lactic dehydrogenase in brain tissue, were measured. The results showed that acupoint irradiation with a semiconductor laser can improve energy metabolism, enhance the expression of GAP-43, increase the levels of expression of serum SOD, and decrease the serum MDA content in a rat model of focal CIR, suggesting the mechanism for reduction of CIR injury.

  2. Distinct metabolic responses of an ovarian cancer stem cell line.

    Science.gov (United States)

    Vermeersch, Kathleen A; Wang, Lijuan; McDonald, John F; Styczynski, Mark P

    2014-12-18

    Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues. Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations. The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to

  3. The response of cerebral cortex to haemorrhagic damage: experimental evidence from a penetrating injury model.

    Directory of Open Access Journals (Sweden)

    Sivaraman Purushothuman

    Full Text Available Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer's disease. In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3-5 months. Brains were examined after 1-30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP, for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer's disease was examined with the same techniques. Needlestick injury induced long-lasting changes-haem deposition, cell death, plaque-like deposits and glial invasion-along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the

  4. Apparent brain temperature imaging with multi-voxel proton magnetic resonance spectroscopy compared with cerebral blood flow and metabolism imaging on positron emission tomography in patients with unilateral chronic major cerebral artery steno-occlusive disease

    Energy Technology Data Exchange (ETDEWEB)

    Nanba, Takamasa; Nishimoto, Hideaki; Murakami, Toshiyuki; Fujiwara, Shunrou; Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Iwate (Japan); Yoshioka, Yoshichika [Osaka University, Open and Transdisciplinary Research Initiatives, Osaka (Japan); Sasaki, Makoto; Uwano, Ikuko [Iwate Medical University, Institute for Biomedical Science, Iwate (Japan); Terasaki, Kazunori [Iwate Medical University, Cyclotron Research Center, Iwate (Japan)

    2017-09-15

    The purpose of the present study was to determine whether apparent brain temperature imaging using multi-voxel proton magnetic resonance (MR) spectroscopy correlates with cerebral blood flow (CBF) and metabolism imaging in the deep white matter of patients with unilateral chronic major cerebral artery steno-occlusive disease. Apparent brain temperature and CBF and metabolism imaging were measured using proton MR spectroscopy and {sup 15}O-positron emission tomography (PET), respectively, in 35 patients. A set of regions of interest (ROIs) of 5 x 5 voxels was placed on an MR image so that the voxel row at each edge was located in the deep white matter of the centrum semiovale in each cerebral hemisphere. PET images were co-registered with MR images with these ROIs and were re-sliced automatically using image analysis software. In 175 voxel pairs located in the deep white matter, the brain temperature difference (affected hemisphere - contralateral hemisphere: ΔBT) was correlated with cerebral blood volume (CBV) (r = 0.570) and oxygen extraction fraction (OEF) ratios (affected hemisphere/contralateral hemisphere) (r = 0.641). We excluded voxels that contained ischemic lesions or cerebrospinal fluid and calculated the mean values of voxel pairs in each patient. The mean ΔBT was correlated with the mean CBF (r = - 0.376), mean CBV (r = 0.702), and mean OEF ratio (r = 0.774). Apparent brain temperature imaging using multi-voxel proton MR spectroscopy was correlated with CBF and metabolism imaging in the deep white matter of patients with unilateral major cerebral artery steno-occlusive disease. (orig.)

  5. High specificity in plant leaf metabolic responses to arbuscular mycorrhiza.

    Science.gov (United States)

    Schweiger, Rabea; Baier, Markus C; Persicke, Marcus; Müller, Caroline

    2014-05-22

    The chemical composition of plants (phytometabolome) is dynamic and modified by environmental factors. Understanding its modulation allows to improve crop quality and decode mechanisms underlying plant-pest interactions. Many studies that investigate metabolic responses to the environment focus on single model species and/or few target metabolites. However, comparative studies using environmental metabolomics are needed to evaluate commonalities of chemical responses to certain challenges. We assessed the specificity of foliar metabolic responses of five plant species to the widespread, ancient symbiosis with a generalist arbuscular mycorrhizal fungus. Here we show that plant species share a large 'core metabolome' but nevertheless the phytometabolomes are modulated highly species/taxon-specifically. Such a low conservation of responses across species highlights the importance to consider plant metabolic prerequisites and the long time of specific plant-fungus coevolution. Thus, the transferability of findings regarding phytometabolome modulation by an identical AM symbiont is severely limited even between closely related species.

  6. Secondary metabolism responses in two Pisum sativum L. cultivars ...

    African Journals Online (AJOL)

    The present study was carried out to investigate the Fe deficiency effect on the secondary metabolism responses in two Pisum sativum cultivars characterized by different tolerance to Fe deficiency. Previous study investigating the physiological responses to Fe deficiency in these two pea cultivars showed that Kelvedon was ...

  7. Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men

    DEFF Research Database (Denmark)

    Hashimoto, Takeshi; Tsukamoto, Hayato; Takenaka, Saki

    2018-01-01

    High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake....... Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine differences across the brain for lactate (a-v difflactate), glucose (diffglucose), oxygen (diffoxygen...

  8. Cerebral and myocardial blood flow responses to hypercapnia and hypoxia in humans.

    Science.gov (United States)

    Beaudin, Andrew E; Brugniaux, Julien V; Vöhringer, Matthias; Flewitt, Jacqueline; Green, Jordin D; Friedrich, Matthias G; Poulin, Marc J

    2011-10-01

    In humans, cerebrovascular responses to alterations in arterial Pco(2) and Po(2) are well documented. However, few studies have investigated human coronary vascular responses to alterations in blood gases. This study investigated the extent to which the cerebral and coronary vasculatures differ in their responses to euoxic hypercapnia and isocapnic hypoxia in healthy volunteers. Participants (n = 15) were tested at rest on two occasions. On the first visit, middle cerebral artery blood velocity (V(P)) was assessed using transcranial Doppler ultrasound. On the second visit, coronary sinus blood flow (CSBF) was measured using cardiac MRI. For comparison with V(P), CSBF was normalized to the rate pressure product [an index of myocardial oxygen consumption; normalized (n)CSBF]. Both testing sessions began with 5 min of euoxic [end-tidal Po(2) (Pet(O(2))) = 88 Torr] isocapnia [end-tidal Pco(2) (Pet(CO(2))) = +1 Torr above resting values]. Pet(O(2)) was next held at 88 Torr, and Pet(CO(2)) was increased to 40 and 45 Torr in 5-min increments. Participants were then returned to euoxic isocapnia for 5 min, after which Pet(O(2)) was decreased from 88 to 60, 52 and 45 Torr in 5-min decrements. Changes in V(P) and nCSBF were normalized to isocapnic euoxic conditions and indexed against Pet(CO(2)) and arterial oxyhemoglobin saturation. The V(P) gain for euoxic hypercapnia (%/Torr) was significantly higher than nCSBF (P = 0.030). Conversely, the V(P) gain for isocapnic hypoxia (%/%desaturation) was not different from nCSBF (P = 0.518). These findings demonstrate, compared with coronary circulation, that the cerebral circulation is more sensitive to hypercapnia but similarly sensitive to hypoxia.

  9. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

  10. Hyperbaric oxygen treatment attenuated the decrease in regional glucose metabolism of rats subjected to focal cerebral ischemia: a high resolution positron emission tomography study.

    Science.gov (United States)

    Lou, M; Zhang, H; Wang, J; Wen, S-Q; Tang, Z-Q; Chen, Y-Z; Yan, W-Q; Ding, M-P

    2007-05-11

    Cerebral hypoxia may be the main component of cell damage caused by ischemia. Previous studies demonstrated a neuroprotective effect of early hyperbaric oxygen (HBO) treatment in various animal models of focal cerebral ischemia. Neuropathologic study showed that exposure of HBO may prevent cell death in ischemic cortex. In the present study, we aimed to assess cellular function of ischemic rat brain after HBO treatment by means of a high-resolution positron emission tomography scanner (microPET) used specifically for small animal imaging. The male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO), with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. One hour after ischemia, HBO therapy (3 atm absolute, 1 h) was initiated. Local cerebral glucose utilization in the ischemic area was measured before, 1 h and 3 h after ischemia, with 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. Neurological deficits and infarct volumes were assessed at 24 h after ischemia. Our study showed that early HBO therapy significantly reduced infarct volume of brain 24 h after ischemia. Moreover, glucose utilization in the ischemic area underwent a severe decrease during 1-3 h after MCAO, while the early HBO treatment significantly attenuated the decrease in cerebral metabolic rate of glucose in the ischemic core of the cortex compared with controls. We report for the first time the application of microPET to quantify the rates of glucose metabolism in the ischemic core of rats exposed to HBO. Our results suggest that the early exposure of HBO can partially reverse the downward trend for glucose utilization in the ischemic core, which might contribute to the reported beneficial effects of early HBO therapy on permanent cerebral ischemia.

  11. Effects of caprylic triglyceride on cognitive performance and cerebral glucose metabolism in mild Alzheimer’s disease: a single-case observation

    Directory of Open Access Journals (Sweden)

    Brian Andrew Farah

    2014-07-01

    Full Text Available Objective: To examine the effect of 109 days of caprylic triglyceride (CT in a 70 year-old male with mild Alzheimer’s disease (AD. Background: Cerebral metabolism is limited to glucose under most conditions, and diminished cerebral glucose metabolism is a characteristic feature of AD. Another substrate available for cerebral metabolism is ketone bodies. Ketone bodies are normally derived from fat stores under conditions of low glucose availability as an alternative energy substrate to glucose. Ketone bodies can also be produced by oral administration of CT. Prior studies suggest that the alternative energy source of CT may improve cognitive function due to mild to moderate AD, by circumventing the diminished glucose metabolism. Method: The effect of CT was analyzed in a single-case of mild AD with cognitive alterations in an open label study. Study outcomes included the Montreal Cognitive Assessment (MoCA, Mini Mental State Exam (MMSE and 18-Fluorodeoxyglucose (18F Positron Emission Tomography (FDG PET scans. Results: After 109 days of CT, MoCA scores changed from a baseline value of 24 to 28, and MMSE scores changed from 23 to 28. No changes were observed on FDG PET scans. Conclusion: The results suggest that, in a case of mild AD, CT may have affected cognitive function, assessed by means of MMSE and MoCA, although glucose uptake and metabolism remained unchanged.

  12. Effect of Stress-free Therapy on Cerebral Blood Flow: Comparisons among patients with metabolic cardiovascular disease, healthy subjects and placebo-treated subjects

    Science.gov (United States)

    Ryotokuji, Kenji; Ishimaru, Keisou; Kihara, Kazuhiko; Namiki, Yoshihisa; Nakashima, Takuma; Otani, Satoru

    2014-01-01

    Background and aims: We have developed a Stress-free Therapy® device wherein “Pinpoint Plantar Long-wavelength Infrared Light Irradiation (PP-LILI)” increases peripheral-deep body temperature and blood flow volume and stabilizes blood pressure as well as significantly reduces stress hormones such as adrenocorticotrophic hormone and cortisol without using drugs. Moreover, we have found this therapy to significantly improve blood glucose and insulin resistance in patients with type 2 diabetes. Based on this background of clinical efficacy, we validated changes in cerebral blood flow in patients with metabolic cardiovascular disease and examined the efficacy of Stress-free Therapy® on cerebral blood flow as compared to that in healthy control subjects and placebo-treated patients. Results: The change in cerebral blood flow volume during 15-minute PP-LILI was 5.1 ± 1.8 mL/min in patients with metabolic cardiovascular disease, showing a significant increase (P<0.05) of 3.1 mL/min as compared with the mean blood flow value after resting for 15 minutes. Conclusions: Our results suggested Stress-free Therapy® to significantly increase cerebral blood flow, possibly leading to the prevention of metabolic cardiovascular disease. PMID:24771966

  13. Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.

    Science.gov (United States)

    Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato

    2017-01-29

    Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Complexity of the cell-cell interactions in the innate immune response after cerebral ischemia.

    Science.gov (United States)

    Cuartero, María I; Ballesteros, Iván; Lizasoain, Ignacio; Moro, María A

    2015-10-14

    In response to brain ischemia a cascade of signals leads to the activation of the brain innate immune system and to the recruitment of blood borne derived cells to the ischemic tissue. These processes have been increasingly shown to play a role on stroke pathogenesis. Here, we discuss the key features of resident microglia and different leukocyte subsets implicated in cerebral ischemia with special emphasis of neutrophils, monocytes and microglia. We focus on how leukocytes are recruited to injured brain through a complex interplay between endothelial cells, platelets and leukocytes and describe different strategies used to inhibit their recruitment. Finally, we discuss the possible existence of different leukocyte subsets in the ischemic tissue and the repercussion of different myeloid phenotypes on stroke outcome. The knowledge of the nature of these heterogeneous cell-cell interactions may open new lines of investigation on new therapies to promote protective immune responses and tissue repair after cerebral ischemia or to block harmful responses. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    Directory of Open Access Journals (Sweden)

    Suzan Wopereis

    Full Text Available BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. METHODOLOGY: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. CONCLUSIONS: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

  16. Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

    2009-12-15

    Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

  17. Cerebral metabolic and structural alterations in hereditary spastic paraplegia with thin corpus callosum assessed by MRS and DTI

    Energy Technology Data Exchange (ETDEWEB)

    Dreha-Kulaczewski, Steffi [Georg August University, Department of Pediatrics and Pediatric Neurology, Faculty of Medicine, Goettingen (Germany); Georg August University, MR Research in Neurology and Psychiatry, Goettingen (Germany); Dechent, Peter; Helms, Gunther [Georg August University, MR Research in Neurology and Psychiatry, Goettingen (Germany); Frahm, Jens [Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut fuer Biophysikalische Chemie, Goettingen (Germany); Gaertner, Jutta; Brockmann, Knut [Georg August University, Department of Pediatrics and Pediatric Neurology, Faculty of Medicine, Goettingen (Germany)

    2006-12-15

    Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations. To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI). While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation - histopathological changes known to occur in HSP-TCC. Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking. (orig.)

  18. Host metabolic responses to Plasmodium falciparum infections evaluated by (1)H NMR metabolomics.

    Science.gov (United States)

    Sengupta, Arjun; Ghosh, Soumita; Das, Bidyut K; Panda, Abhinash; Tripathy, Rina; Pied, Sylviane; Ravindran, B; Pathak, Sulabha; Sharma, Shobhona; Sonawat, Haripalsingh M

    2016-10-18

    The human malarial parasite Plasmodium falciparum causes the most severe forms of malarial infections, which include cerebral malaria and various organ dysfunctions amongst adults in India. So far no dependable clinical descriptor is available that can distinguish cerebral malaria from other symptomatically similar diseases such as sepsis and encephalitis. This study aims at evaluating the differential metabolic features of plasma samples from P. falciparum patients with varying severities, and patients suffering from symptomatically similar diseases. (1)H Nuclear Magnetic Resonance (NMR) based metabolic profiling of the plasma of the infected individuals and the control population was performed. The differences in the plasma profiles were evaluated through multivariate statistical analyses. The results suggest malaria-specific elevation of plasma lipoproteins. Such an increase was absent in control populations. In addition, cerebral malaria patients exhibited a decrease in plasma glycoproteins; such a reduction was not observed in malarial patients without cerebral symptoms. The data presented here indicates that the metabolism and/or transport of the plasma lipids is specifically perturbed by malarial infections. The differential perturbation of the plasma glycoprotein levels in cerebral malaria patients may have important implications in the diagnosis of cerebral malaria.

  19. Visualization and quantification of cerebral metabolic fluxes of glucose in awake mice.

    Science.gov (United States)

    Sugiura, Yuki; Honda, Kurara; Kajimura, Mayumi; Suematsu, Makoto

    2014-04-01

    Biotransformation of glucose in organs includes multiple pathways, while quantitative evaluation of percentages of its utilization for individual pathways and their spatial heterogeneity in vivo remain unknown. Imaging MS (IMS) and metabolomics combined with a focused microwave irradiation for rapidly fixing tissue metabolism allowed us to quantify and visualize metabolic fluxes of glucose-derived metabolites in the mouse brain in vivo. At 15 min after the intraperitoneal injection of (13) C6 -labeled glucose, the mouse brain was exposed to focused microwave irradiation, which can stop brain metabolism within 1 s. Quantification of metabolic intermediates containing (13) C atoms revealed that a majority of the (13) C6 -glucose was diverted into syntheses of glutamate, lactate, and uridine diphosphate (UDP)-glucose. IMS showed that regions rich in glutaminergic neurons exhibited a large signal of (13) C2 -labeled glutamate. On the other hand, the midbrain region was enriched with an intensive (13) C6 -labeled UDP-glucose signal, suggesting an active glycogen synthesis. Collectively, application of the current method makes it possible to examine the fluxes of glucose metabolism in a region-specific manner. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J.C.; Hagman, J.; Buchsbaum, M.S.; Blinder, B.; Derrfler, M.; Tai, W.Y.; Hazlett, E.; Sicotte, N. (Univ. of California, Irvine (USA))

    1990-03-01

    Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using (18F)-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion that bulimia is a diagnostic grouping distinct from these disorders.

  1. Visual dependence affects postural sway responses to continuous visual field motion in individuals with cerebral palsy.

    Science.gov (United States)

    Yu, Yawen; Lauer, Richard T; Tucker, Carole A; Thompson, Elizabeth D; Keshner, Emily A

    2018-01-17

    The current study aimed to explore the impact of visual dependence on sensorimotor coupling of postural sway and visual motion in adults and teens with spastic cerebral palsy (CP). We hypothesized that individuals with CP would exhibit greater magnitudes of sway than healthy individuals, and the presence of visual dependence (VD) would produce instability in the direction of visual motion. Participants stood in a virtual environment in which the visual scene remained static or continuously rotated 30 degree/second in pitch-up or pitch-down. Increased center of pressure and center of mass responses were observed in the direction of visual scene motion in those with CP. Those with VD exhibited reduced frequency responses in anterior-posterior direction than those who were visually independent. VD suggests deficient sensorimotor integration that could contribute to postural instability and reduced motor function. Individuals with CP who are visually dependent may benefit from more sensory focused rehabilitation strategies. AP, anterior-posterior; CP, cerebral palsy; COM, center of mass; COP, center of pressure; MDF, median frequency; ML, mediolateral; PD, pitch down (nose down) rotation; PU, pitch up (nose up) rotation; RFT, rod and frame test; RMS, root mean square; SLP, slope of the fitted line; TD, typical development; VD, visual dependence; VI, visual independence; VOR, vestibulo-ocular reflex; VPI, visual perceptual impairment.

  2. Individual cerebral metabolic deficits in Alzheimer's disease and amnestic mild cognitive impairment: an FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Del Sole, Angelo; Lecchi, Michela; Lucignani, Giovanni [Unit of Nuclear Medicine, Hospital San Paolo, Institute of Radiological Sciences, University of Milan, Milan (Italy); Clerici, Francesca; Mariani, Claudio; Maggiore, Laura [University of Milan, Center for Research and Treatment on Cognitive Dysfunctions, Institute of Clinical Neurology, Department of Clinical Sciences, ' Luigi Sacco' Hospital, Milan (Italy); Chiti, Arturo [Clinical Institute Humanitas, Nuclear Medicine Department, Milan (Italy); Mosconi, Lisa [New York University School of Medicine, Department of Psychiatry, New York, NY (United States)

    2008-07-15

    The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). [{sup 18}F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 {+-} 8 years) and in 14 AD patients (ten women, age 75 {+-} 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions. (orig.)

  3. Knee jerk responses in infants at high risk for cerebral palsy: an observational EMG study.

    Science.gov (United States)

    Hamer, Elisa G; Dijkstra, Linze J; Hooijsma, Siebrigje J; Zijdewind, Inge; Hadders-Algra, Mijna

    2016-09-01

    Following our clinical observation of tonic responses in response to the knee jerk in infants at very high risk for cerebral palsy (VHR infants), we systematically studied tonic responses, clonus, and reflex irradiation. We questioned (i) whether these responses occurred more often in VHR infants than in typically developing (TD) infants, and (ii) whether they were associated with abnormal general movement quality. Twenty-four VHR and 26 TD infants were assessed around 3 mo corrected age. Surface electromyograms of leg, trunk, neck, and arm muscles were recorded while eliciting the knee jerk. All assessments were video-recorded. VHR infants more often than TD infants showed tonic responses in the ipsilateral quadriceps and hamstring (Mann-Whitney U; P = 0.0005 and P = 0.0009), clonus (Chi-square; P = 0.0005) and phasic responses in the contralateral quadriceps and hamstring (Mann-Whitney U; P = 0.002 and P = 0.0003, respectively). Widespread reflex irradiation occurred in VHR and TD infants. Definitely abnormal general movements and stiff movements were associated with tonic responses (Mann-Whitney U; P = 0.0005, P = 0.007, respectively) and clonus (Mann-Whitney U; P = 0.003 and P = 0.0005) in the ipsilateral quadriceps. Similar to clonus, tonic responses may be regarded as a marker of a loss of supraspinal control. Reflex irradiation primarily is a neurodevelopmental phenomenon of early ontogeny.

  4. Alterations in Cerebral Cortical Glucose and Glutamine Metabolism Precedes Amyloid Plaques in the APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Andersen, Jens V; Christensen, Sofie K; Aldana, Blanca I

    2017-01-01

    in the APPswe/PSEN1dE9 mouse prior to amyloid plaque formation. Acutely isolated cerebral cortical and hippocampal slices of 3-month-old APPswe/PSEN1dE9 and wild-type control mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]glutamine, and tissue extracts were analyzed...... slices of APPswe/PSEN1dE9 mice incubated in media containing [U-(13)C]glucose. No changes in glial [1,2-(13)C]acetate metabolism were observed. Cerebral cortical slices from APPswe/PSEN1dE9 mice exhibited a reduced capacity for uptake and oxidative metabolism of glutamine. Furthermore, the ATP synthesis...... rate tended to be decreased in isolated whole-brain mitochondria of APPswe/PSEN1dE9 mice. Thus, several cerebral metabolic changes are evident in the APPswe/PSEN1dE9 mouse prior to amyloid plaque deposition, including altered glucose metabolism, hampered glutamine processing and mitochondrial...

  5. Metabolic Response to Four Weeks of Muscular Endurance Resistance Training

    Directory of Open Access Journals (Sweden)

    John W. Farrell III

    2017-10-01

    Full Text Available Background: Previous investigations have shown that muscular endurance resistance training (MERT is conducive in improving the onset of blood lactate accumulation (OBLA. However, the metabolic response and time course for adaption is still unclear. Objective: The aims of the current study were to evaluate and track the metabolic response to an individual session of MERT as well as to assess performance adaptations of supplementing an aerobic exercise training program with four weeks of MERT. Methods: Seventeen aerobically active men were randomly assigned to either the experimental (EX or control group (CON, 9 EX and 8 CON. Baseline measures included a graded exercise test (GXT and 1-repetition maximum (1RM testing for leg press (LP, leg curl (LC, and leg extension (LE. CON continued their regular aerobic activity while the EX supplemented their regular aerobic exercise with 4 weeks of MERT. Results: No significant group differences were observed for all pre-training variables. Following four weeks of training no significant differences in cardiorespiratory or metabolic variables were observed for either group. However, significant improvements in LC and LE 1-RM were observed in EX compared to CON. Substantial accumulations in blood lactate were observed following each MERT session. Conclusion: Four weeks of MERT did not improve cardiorespiratory or metabolic variables, but did significantly improve LC and LE. MERT was also observed to induce a blood lactate response similar to that of HIIT. These findings suggest greater than four weeks is need to see metabolic adaptations conducive for improved aerobic performance using MERT.

  6. Fluid provision and metabolic responses to soccer-specific exercise.

    Science.gov (United States)

    Clarke, N D; Drust, B; Maclaren, D P M; Reilly, T

    2008-12-01

    The present study aimed to investigate the impact on metabolism of altering the timing and volume of ingested carbohydrate during soccer-specific exercise. Twelve soccer players performed a soccer-specific protocol on three occasions. On two, 7 ml kg(-1) carbohydrate-electrolyte or placebo were ingested at 0 and 45 min. On a third, the same total volume of carbohydrate-electrolyte was consumed but at 0, 15, 30, 45, 60 and 75 min. Carbohydrate-electrolyte ingestion increased blood glucose, insulin and carbohydrate oxidation, whilst suppressing NEFA, glycerol and fat oxidation (P carbohydrate ingestion elicited similar metabolic responses (P > 0.05). However, consuming fluid in small volumes reduced the sensation of gut fullness (P carbohydrate consumed is equal, manipulating the timing and volume of ingestion elicits similar metabolic responses. Furthermore, consuming a small volume of fluid at regular intervals reduces the sensation of gut fullness.

  7. Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation.

    Directory of Open Access Journals (Sweden)

    Anders Hougaard

    Full Text Available Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks.

  8. Metabolic reprogramming & inflammation: Fuelling the host response to pathogens.

    Science.gov (United States)

    Gleeson, Laura E; Sheedy, Frederick J

    2016-10-01

    Successful immune responses to pathogens rely on efficient host innate processes to contain and limit bacterial growth, induce inflammatory response and promote antigen presentation for the development of adaptive immunity. This energy intensive process is regulated through multiple mechanisms including receptor-mediated signaling, control of phago-lysomal fusion events and promotion of bactericidal activities. Inherent macrophage activities therefore are dynamic and are modulated by signals and changes in the environment during infection. So too does the way these cells obtain their energy to adapt to altered homeostasis. It has emerged recently that the pathways employed by immune cells to derive energy from available or preferred nutrients underline the dynamic changes associated with immune activation. In particular, key breakpoints have been identified in the metabolism of glucose and lipids which direct not just how cells derive energy in the form of ATP, but also cellular phenotype and activation status. Much of this comes about through altered flux and accumulation of intermediate metabolites. How these changes in metabolism directly impact on the key processes required for anti-microbial immunity however, is less obvious. Here, we examine the 2 key nutrient utilization pathways employed by innate cells to fuel central energy metabolism and examine how these are altered in response to activation during infection, emphasising how certain metabolic switches or 'reprogramming' impacts anti-microbial processes. By examining carbohydrate and lipid pathways and how the flux of key intermediates intersects with innate immune signaling and the induction of bactericidal activities, we hope to illustrate the importance of these metabolic switches for protective immunity and provide a potential mechanism for how altered metabolic conditions in humans such as diabetes and hyperlipidemia alter the host response to infection. Copyright © 2016. Published by Elsevier Ltd.

  9. Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhang

    2014-06-01

    Full Text Available Erythropoietin (EPO regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR, suggest the potential for EPO response in metabolism and disease.

  10. Slow pupillary light responses in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and neurological outcome.

    Science.gov (United States)

    Hamer, Elisa G; Vermeulen, R Jeroen; Dijkstra, Linze J; Hielkema, Tjitske; Kos, Claire; Bos, Arend F; Hadders-Algra, Mijna

    2016-12-01

    Having observed slow pupillary light responses (PLRs) in infants at high risk of cerebral palsy, we retrospectively evaluated whether these were associated with specific brain lesions or unfavourable outcomes. We carried out neurological examinations on 30 infants at very high risk of cerebral palsy five times until the corrected age of 21 months, classifying each PLR assessment as normal or slow. The predominant reaction during development was determined for each infant. Neonatal brain scans were classified based on the type of brain lesion. Developmental outcome was evaluated at 21 months of corrected age with a neurological examination, the Bayley Scales of Infant Development Second Edition and the Infant Motor Profile. Of the 30 infants, 16 developed cerebral palsy. Predominantly slow PLRs were observed in eight infants and were associated with periventricular leukomalacia (p = 0.007), cerebral palsy (p = 0.039), bilateral cerebral palsy (p = 0.001), poorer quality of motor behaviour (p slow PLR in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and poorer developmental outcome. Slow PLR might be an expression of white matter damage, resulting in dysfunction of the complex cortico-subcortical circuitries. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. Long-term salt stress responsive growth, carbohydrate metabolism ...

    African Journals Online (AJOL)

    We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

  12. Structural and metabolic responses of Ceratophyllum demersum to ...

    African Journals Online (AJOL)

    Eutrophication in water bodies affects the growth of aquatic plants. In this study, we conducted static experiments to better understand the structural and metabolic responses of Ceratophyllum demersum under eutrophication conditions. The anatomical structure, nitrogen (N) and phosphorous (P) levels in tissue, ...

  13. The interplay between central metabolism and innate immune responses

    NARCIS (Netherlands)

    Cheng, S.C.; Joosten, L.A.B.; Netea, M.G.

    2014-01-01

    A growing body of recent studies bring into light an important cross-talk between immune response and metabolism not only at the level of the organism as a whole, but also at the level of the individual cells. Cellular bioenergetics functions not only as a power plant to fuel up the cells, but the

  14. Modeling metabolic response to changes of enzyme amount in ...

    African Journals Online (AJOL)

    Based on the work of Hynne et al. (2001), in an in silico model of glycolysis, Saccharomyces cerevisiae is established by introducing an enzyme amount multiple factor (.) into the kinetic equations. The model is aimed to predict the metabolic response to the change of enzyme amount. With the help of .α, the amounts of ...

  15. Tolerance level and metabolic response of Clarias gariepinus ...

    African Journals Online (AJOL)

    Potassium permanganate is one of the widely used chemicals in aquaculture, its usage if not properly controlled may stress the cultured fish. This study examined the metabolic responses of C. gariepinus fingerlings to stress due to potassium permanganate toxicity. Fingerlings of C. gariepinus of the same parental stock ...

  16. Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, R.S. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Middleton, M.R. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Blesing, C.; Patel, K.; Warner, N. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Marshall, R.E.K.; Maynard, N.D. [Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); Bradley, K.M. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); Gleeson, F.V. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom)

    2012-09-15

    Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV{sub max} (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low. (orig.)

  17. In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

    Science.gov (United States)

    Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R; Öz, Gülin

    2015-02-01

    Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

  18. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    -photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  19. The Bidirectional Relationship between Metabolism and Immune Responses.

    Science.gov (United States)

    Raval, Forum M; Nikolajczyk, Barbara S

    Immunometabolism investigates the multiple links between the immune system and metabolism. One main focus of immunometabolism investigates how obesity impacts the immune system and pro-inflammatory immune cell function, leading to metabolic diseases, including type 2 diabetes (T2D). The second focus stresses the metabolic changes that dictate immune cell activation. Several groups have studied these two arms of the field individually, but work that integrates both topics will be required to develop an accurate understanding of how immune cells and metabolic pathways collaborate in obesity and obesity-associated T2D. Investigations of the relationships among obesity-induced changes in the nutritional environment, immune cell activation, and immune cell metabolism may lead to novel and efficacious therapies for obesity-associated disorders such as insulin resistance (IR) and T2D. This review outlines recent insights into two related processes: 1. the role that energy utilization plays in immune responses and 2. the immune cell functions that drive obesity and T2D. Herein, we begin to consider how shifts in available fuel sources in obesity and T2D impact the immune response to both pathogens and chronic over nutrition.

  20. Regional cerebral glucose metabolic changes in oculopalatal myoclonus: implication for neural pathways, underlying the disorder

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Moon, So Young; Kim, Ji Soo; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    Palatal myoclonus (PM) is characterized by rhythmic involuntary jerky movements of the soft palate of the throat. When associated with eye movements, it is called oculopalatal myoclonus (OPM). Ordinary PM is characterized by hypertrophic olivary degeneration, a trans-synaptic degeneration following loss of neuronal input to the inferior olivary nucleus due to an interruption of the Guillain-Mollaret triangle usually by a hemorrhage. However, the neural pathways underlying the disorder are uncertain. In an attempt to understand the pathologic neural pathways, we examined the metabolic correlates of this tremulous condition. Brain FDG PET scans were acquired in 8 patients with OPM (age, 49.9{+-}4.6 y: all males: 7 with pontine hemorrhage, 1 with diffuse brainstem infarction) and age-matched 50 healthy males (age, 50.7{+-} 9.0) and the regional glucose metabolism compared using SPM99. For group analysis, the hemispheres containing lesions were assigned to the right side of the brain. Patients with OPM had significant hypometabolism in the ipsilateral (to the lesion) brainstem and superior temporal and parahippocampal gyri (P < 0.05 corrected, k = 100). By contrast, there was significant hypermetabolism in the contralateral middle and inferior temporal gyri, thalamus, middle frontal gyrus and precuneus (P < 0.05 corrected, k=l00). Our data demonstrate the distinct metabolic changes between several ipsilateral and contralateral brain regions (hypometabolism vs. hypermetabolism) in patients with OPM. This may provide clues for understanding the neural pathways underlying the disorder.

  1. The change in cerebral glucose metabolism after electroacupuncture: a possible marker to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa.

    Science.gov (United States)

    Liu, Tao-Tao; Hong, Qing-Xiong; Xiang, Hong-Bing

    2015-01-01

    Some reports have demonstrated that deep brain stimulation (DBS) is a promising treatment for patients who suffer from intractable anorexia nervosa. However, the nature of DBS may not be viewed as a standard clinical treatment option for anorexia nervosa because of the unpredictable outcome before DBS. Just like DBS in the brain, electroacupuncture at acupoints is also efficient in treating refractory anorexia nervosa. Some neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) had revealed that both DBS and electroacupuncture at acupoints with electrical stimulation are related to the changes in cerebral glucose metabolism. Therefore, we hypothesize that the changes in cerebral glucose metabolism after electroacupuncture might be useful to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa.

  2. Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex.

    Science.gov (United States)

    Villa, R F; Gorini, A; Hoyer, S

    2006-11-01

    The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

  3. Is there an accurate method to measure metabolic requirement of institutionalized children with spastic cerebral palsy?

    Science.gov (United States)

    Lee, Siu Pik Peggy; Cheung, Ka Ming; Ko, Chun Hung; Chiu, Heung Chin

    2011-07-01

    This study hypothesized that there is no difference between energy expenditure measured by indirect calorimetry (IC) and that estimated by predicted formulas compared with the actual intake of children with spastic cerebral palsy (CP). Fifteen children aged 3 to 18 years with spastic CP and associated complications were recruited. IC was used to measure mean energy expenditure (MEE) compared with 3 predicted equations for energy expenditure (PEE), including body surface area (BSA), the recommended daily allowance (RDA), and an equation designed specifically for patients with CP. Friedman and paired t tests were used to examine the variance between PEE and MEE. Intraclass correlation coefficient (ICC) was used to explore the correlation between MEE and PEE. The pretest and posttest core temperatures were compared using the Wilcoxon signed rank test. Mean ± standard deviation MEE was 800.5 ± 295.7 kcal/d; BSA was 1,213.4 ± 171.2 kcal/d; RDA was 1,928.1 ± 341.0 kcal/d; and CP was 1,603.1 ± 215.8 kcal/d. The actual diet intake provided 935.3 ± 222.9 kcal/d. Post hoc analysis revealed a significant difference between mean MEE and PEE (P children with spastic CP.

  4. Determining the Precise Cerebral Response to Acupuncture: An Improved fMRI Study

    Science.gov (United States)

    Shan, Baoci; Li, Yongzhong; Li, Lin; Xue, Jingquan; Nie, Binbin

    2012-01-01

    Background In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors. Objective To obtain more precise and accurate cerebral fMRI mapping of acupuncture. Design and Setting A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China. Participants Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D. Interventions Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI. Results Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas. Conclusions The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results. PMID:23152865

  5. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  6. The brain relaxation and cerebral metabolism in stroke volume variation-directed fluid therapy during supratentorial tumors resection: crystalloid solution versus colloid solution.

    Science.gov (United States)

    Xia, Juan; He, Zhiyong; Cao, Xiaoying; Che, Xuehua; Chen, Liang; Zhang, Jun; Liang, Weimin

    2014-10-01

    Compared with goal-directed crystalloid therapy, goal-directed colloid therapy during high-risk surgery may improve postoperative outcome. Whether intraoperative fluid therapy based on goal-directed protocol with different types of fluid has distinctive effects on brain relaxation and cerebral metabolism during craniotomy remains unclear. Forty patients with supratentorial brain tumors undergoing craniotomy were randomly assigned to either a Ringer's Lactate-based goal-directed group (LR group, n=20) or a 6% hydroxyethyl starch-based goal-directed group (HES group, n=20). The goal was achieved by maintaining a target stroke volume variation (SVVcerebral metabolism variables (jugular venous oxygen saturation [SjvO(2)], arterial-jugular venous differences in oxygen [CajvO(2)], glucose [A-JvGD], lactate [A-JvLD], and cerebral extraction ratio for oxygen [CERO(2)]) and fluid volumes. There is no significant difference between the LR and HES groups on brain relaxation scales (P=0.845), or measures of cerebral oxygenation and metabolism. Intragroup comparisons showed that CERO(2) increased by 14.3% (P=0.009, LR group) and 13.2% (P=0.032, HES group), respectively, and SjvO(2) was decreased by 8.8% (P=0.016, LR group) and 8.1% (P=0.026, HES group), respectively, after tumor removal, compared with baseline. During surgery, the LR group (3070±1138 mL) received more fluid than the HES group (2041±758 mL, P=0.002). In patients undergoing supratentorial tumor resection, goal-directed HES therapy was not superior to goal-directed LR therapy for brain relaxation or cerebral metabolism, although less fluid was needed to maintain the target SVV in the HES-based group than in the LR-based group.

  7. Simvastatin Combined with Antioxidant Attenuates the Cerebral Vascular Endothelial Inflammatory Response in a Rat Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Wang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

  8. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema.

    Science.gov (United States)

    Siegel, Arthur J; Forte, Sophie S; Bhatti, Nasir A; Gelda, Steven E

    2016-03-09

    Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema and facilitate a full recovery without neurological complications.

  9. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Energy Technology Data Exchange (ETDEWEB)

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Pijnenburg, Yolande A.L.; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2015-10-15

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [{sup 18}F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

  10. Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Porrino, L.J.; Domer, F.R.; Crane, A.M.; Sokoloff, L.

    1988-05-01

    The 2-(/sup 14/C)deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.

  11. [Clinical effect of high pressure oxygen and Butylphthalide in the recovery of cerebral metabolism after carbon monoxide poisoning].

    Science.gov (United States)

    Han, Q; Guo, X T; Zhang, H H; Tian, R; Gao, X; Zhang, Z Q

    2017-08-20

    Objective: To study the clinical effect of high pressure oxygen and Butylphthalide in the recovery of cerebral metabolism after carbon monoxide poisoning. Methods: 84 patients treated from May 2014 to May 2016 in our hospital were selected. The subjects were randomly and equally divided into two groups. The control group adopted the conventional therapy and high pressure oxygen; on the basis, the observation group also took Butylphthalide. The clinical effect, duration of coma, recovery of consciousness, incidence rate of delayed encephalopathy was observed. After 1m of treatment, the HDS point was evaluated. Results: The total effective rate of control group (76.19%, 32/42) was lower than that of observation group (95.24%, 40/42) ( P incidence rate of delayed encephalopathy for observation group was better than that of control group ( P <0.05) . The HDS point for observation group was even higher than that of control group ( P <0.05) . Conclusion: The high pressure oxygen and butylphthalide can improve the clinical effective rate, shorten the duration of coma and promote the patient's recovery of consciousness. It is worthy of clinical promotion.

  12. Noninvasive quantification of cerebral metabolic rate for glucose in rats using (18)F-FDG PET and standard input function.

    Science.gov (United States)

    Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

    2015-10-01

    Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed (18)F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIF(NS)) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF(1S)). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIF(NS)-, and EIF(1S)-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIF(NS) was highly correlated with those derived from AIF and EIF(1S). Preliminary comparison between AIF and EIF(NS) in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIF(NS) method might serve as a noninvasive substitute for individual AIF measurement.

  13. Fetal and maternal metabolic responses to exercise during pregnancy.

    Science.gov (United States)

    Mottola, Michelle F; Artal, Raul

    2016-03-01

    Pregnancy is characterized by physiological, endocrine and metabolic adaptations creating a pseudo-diabetogenic state of progressive insulin resistance. These adaptations occur to sustain continuous fetal requirements for nutrients and oxygen. Insulin resistance develops at the level of the skeletal muscle, and maternal exercise, especially activity involving large muscle groups improve glucose tolerance and insulin sensitivity. We discuss the maternal hormonal and metabolic changes associated with a normal pregnancy, the metabolic dysregulation that may occur leading to gestational diabetes mellitus (GDM), and the consequences to mother and fetus. We will then examine the acute and chronic (training) responses to exercise in the non-pregnant state and relate these alterations to maternal exercise in a low-risk pregnancy, how exercise can be used to regulate glucose tolerance in women at risk for or diagnosed with GDM. Lastly, we present key exercise guidelines to help maintain maternal glucose regulation and suggest future research directions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. The deep cerebral stimulation of the under thalamic nucleus modifies the cerebral metabolism in {sup 18}FDG-Tep of obsessive compulsive patients; La stimulation cerebrale profonde du noyau sous thalamique modifie le metabolisme cerebral en 18FDG-TEP des patients obsessionnels compulsifs

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, F.; Garin, E. [Service de medecine nucleaire, centre Eugene-Marquis, Rennes, (France); Verin, M.; Peron, J. [service de neurologie, CHU Pontchaillou, Rennes, (France); Mallet, L.; Yelnik, J. [Inserm, Avenir Team, Behavior, Emotion and Basal Ganglia, IFR 70, Pitie-Salpetriere, Paris, (France); Kreps, M.O. [Inserm U796, service de psychiatrie, hopital Sainte-Anne, Paris, (France); Drapier, D.; Millet, B. [service de psychiatrie adulte, centre hospitalier Guillaume-Regnier, Rennes, (France)

    2009-05-15

    The aim of this work was to find again this orbito-frontal hyper metabolism among the resistant obsessive compulsive disorder patients that are going to benefit of a deep cerebral stimulation of the under thalamus nucleus and to demonstrate that this new therapy approach leads a reduction of the metabolism in this area in correlation with the clinical improvement. It is about the first study realized in isotopic functional imaging on ten resistant compulsive disorder patients treated by bilateral deep cerebral stimulation of the under thalamus nucleus. It shows that the treatment efficiency is in relation with a reduction of the glucide metabolism in the right orbito-frontal cortex. It suggests equally that the under thalamus nucleus would be functionally linked to the orbito-frontal cortex. (N.C.)

  15. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans.

    Science.gov (United States)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M; Holstein-Rathlou, Niels-Henrik; Møller, Kirsten

    2015-07-01

    Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. This was performed at baseline and repeated after a 4-h intravenous LPS infusion. The assessments of dCA were based on transfer function analysis of spontaneous oscillations between MAP and middle cerebral artery blood flow velocity measured by transcranial Doppler ultrasound in the low frequency range (0.07-0.20 Hz). Prior to LPS, noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional neuroprotective effect by enhancing dCA in patients with early sepsis. © 2015 Wiley Publishing Asia Pty Ltd.

  16. Metabolic factors affecting the inflammatory response of periparturient dairy cows.

    Science.gov (United States)

    Sordillo, Lorraine M; Contreras, G A; Aitken, Stacey L

    2009-06-01

    Dairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.

  17. Disparate metabolic response to fructose feeding between different mouse strains.

    Science.gov (United States)

    Montgomery, M K; Fiveash, C E; Braude, J P; Osborne, B; Brown, S H J; Mitchell, T W; Turner, N

    2015-12-22

    Diets enriched in fructose (FR) increase lipogenesis in the liver, leading to hepatic lipid accumulation and the development of insulin resistance. Previously, we have shown that in contrast to other mouse strains, BALB/c mice are resistant to high fat diet-induced metabolic deterioration, potentially due to a lack of ectopic lipid accumulation in the liver. In this study we have compared the metabolic response of BALB/c and C57BL/6 (BL6) mice to a fructose-enriched diet. Both strains of mice increased adiposity in response to FR-feeding, while only BL6 mice displayed elevated hepatic triglyceride (TAG) accumulation and glucose intolerance. The lack of hepatic TAG accumulation in BALB/c mice appeared to be linked to an altered balance between lipogenic and lipolytic pathways, while the protection from fructose-induced glucose intolerance in this strain was likely related to low levels of ER stress, a slight elevation in insulin levels and an altered profile of diacylglycerol species in the liver. Collectively these findings highlight the multifactorial nature of metabolic defects that develop in response to changes in the intake of specific nutrients and the divergent response of different mouse strains to dietary challenges.

  18. Slow pupillary light responses in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and neurological outcome

    NARCIS (Netherlands)

    Hamer, E.G.; Vermeulen, R.J.; Dijkstra, L.J.; Hielkema, T.; Kos, C.; Bos, A.F; Hadders-Algra, M.

    2016-01-01

    AIM: Having observed slow pupillary light responses (PLRs) in infants at high risk of cerebral palsy, we retrospectively evaluated whether these were associated with specific brain lesions or unfavourable outcomes. METHODS: We carried out neurological examinations on 30 infants at very high risk of

  19. Slow pupillary light responses in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and neurological outcome

    NARCIS (Netherlands)

    Hamer, Elisa G.; Vermeulen, R. Jeroen; Dijkstra, Linze J.; Hielkema, Tjitske; Kos, Claire; Bos, Arend F.; Hadders-Algra, Mijna

    2016-01-01

    Aim: Having observed slow pupillary light responses (PLRs) in infants at high risk of cerebral palsy, we retrospectively evaluated whether these were associated with specific brain lesions or unfavourable outcomes. Methods: We carried out neurological examinations on 30 infants at very high risk of

  20. Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions

    Directory of Open Access Journals (Sweden)

    Alexis M. Stranahan

    2012-01-01

    Full Text Available The hypothalamus is an essential relay in the neural circuitry underlying energy metabolism that needs to continually adapt to changes in the energetic environment. The neuroendocrine control of food intake and energy expenditure is associated with, and likely dependent upon, hypothalamic plasticity. Severe disturbances in energy metabolism, such as those that occur in obesity, are therefore likely to be associated with disruption of hypothalamic transcriptomic plasticity. In this paper, we investigated the effects of two well-characterized antiaging interventions, caloric restriction and voluntary wheel running, in two distinct physiological paradigms, that is, diabetic (db/db and nondiabetic wild-type (C57/Bl/6 animals to investigate the contextual sensitivity of hypothalamic transcriptomic responses. We found that, both quantitatively and qualitatively, caloric restriction and physical exercise were associated with distinct transcriptional signatures that differed significantly between diabetic and non-diabetic mice. This suggests that challenges to metabolic homeostasis regulate distinct hypothalamic gene sets in diabetic and non-diabetic animals. A greater understanding of how genetic background contributes to hypothalamic response mechanisms could pave the way for the development of more nuanced therapeutics for the treatment of metabolic disorders that occur in diverse physiological backgrounds.

  1. Ictal but not interictal epileptic discharges activate astrocyte endfeet and elicit cerebral arteriole responses.

    Directory of Open Access Journals (Sweden)

    Marta eGomez-Gonzalo

    2011-06-01

    Full Text Available Activation of astrocytes by neuronal signals plays a central role in the control of neuronal activity-dependent blood flow changes in the normal brain. The cellular pathways that mediate neurovascular coupling in the epileptic brain remain, however, poorly defined. In a cortical slice model of epilepsy, we found that the ictal, seizure-like discharge, and only to a minor extent the interictal discharge, evokes both a Ca2+ increase in astrocyte endfeet and a vasomotor response. We also observed that rapid ictal discharge-induced arteriole responses were regularly preceded by Ca2+ elevations in endfeet and were abolished by pharmacological inhibition of Ca2+ signals in these astrocyte processes. Under these latter conditions, arterioles exhibited after the ictal discharge only slowly developing vasodilations. The poor efficacy of interictal discharges, compared with ictal discharges, to activate endfeet was confirmed also in the intact in vitro isolated guinea pig brain. Although the possibility of a direct contribution of neurons, in particular in the late response of cerebral blood vessels to epileptic discharges, should be taken into account, our study supports the view that astrocytes are central for neurovascular coupling also in the epileptic brain. The massive endfeet Ca2+ elevations evoked by ictal discharges and the poor response to interictal events represent new information potentially relevant to interpret data from diagnostic brain imaging techniques, such as functional magnetic resonance, utilized in the clinic to localize neural activity and to optimize neurosurgery of untreatable epilepsies.

  2. Biofilm Shows Spatially Stratified Metabolic Responses to Contaminant Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Bin; Majors, Paul D.; Ahmed, B.; Renslow, Ryan S.; Sylvia, Crystal P.; Shi, Liang; Kjelleberg, Staffan; Fredrickson, Jim K.; Beyenal, Haluk

    2012-11-01

    The objective of this study was to elucidate the spatiotemporal responses of live S. oneidensis MR-1 biofilms to U(VI) (uranyl, UO22+) and Cr(VI) (chromate, CrO42-), important environmental contaminants at DOE contaminated sites. Toward this goal, we applied noninvasive nuclear magnetic resonance (NMR) imaging, diffusion, relaxation and spectroscopy techniques to monitor in situ spatiotemporal responses of S. oneidensis biofilms to U(VI) and Cr(VI) exposure in terms of changes in biofilm structures, diffusion properties, and cellular metabolism. Exposure to U(VI) or Cr(VI) did not appear to change the overall biomass distribution but caused changes in the physicochemical microenvironments inside the biofilm as indicated by diffusion measurements. Changes in the diffusion properties of the biofilms in response to U(VI) and Cr(VI) exposure imply a novel function of the extracellular polymeric substances (EPS) affecting the biotransformation and transport of contaminants in the environment. In the presence of U(VI) or Cr(VI), the anaerobic metabolism of lactate was inhibited significantly, although the biofilms were still capable of reducing U(VI) and Cr(VI). Local concentrations of Cr(III)aq in the biofilm suggested relatively high Cr(VI) reduction activities at the top of the biofilm, near the medium-biofilm interface. The depth-resolved metabolic activities of the biofilm suggested higher diversion effects of gluconeogenesis and C1 metabolism pathways at the bottom of the biofilm and in the presence of U(VI). This study provides a noninvasive means to investigate spatiotemporal responses of biofilms, including surface-associated microbial communities in engineering, natural and medical settings, to various environmental perturbations including exposure to environmental contaminants and antimicrobials.

  3. PET measured evoked cerebral blood flow responses in an awake monkey

    Energy Technology Data Exchange (ETDEWEB)

    Perlmutter, J.S.; Lich, L.L.; Margenau, W.; Buchholz, S. (Washington Univ. School of Medicine, St. Louis, MO (USA))

    1991-03-01

    We have developed a method to measure task-related regional cerebral blood flow (BF) responses in an awake, trained monkey using positron emission tomography (PET) and H215O. We trained an animal with operant conditioning using only positive reinforcement to climb unassisted into a modified primate chair that was then positioned in the PET scanner. A special headholder and acrylic skull cap permitted precise placement and accurate repositioning. We measured BF qualitatively with bolus injection of H215O and 40-s scan. Each session included scans at rest interposed with scans during vibration of a forepaw. Regional responses were identified using subtraction image analysis. After global normalization, a resting image was subtracted on a pixel-by-pixel basis from a comparable image collected during vibration. The region of peak response occurred in contralateral sensorimotor cortex with a mean magnitude of 11.6% (+/- 3.2%) of the global mean value for 10 separate experiments, significantly greater than the mean qualitative BF change (0.4 +/- 3.6%; p less than 0.00001) in the same region for seven rest-rest pairs. This newly developed technique forms the basis for a wide variety of experiments.

  4. Acute effects of nimodipine on cerebral vasculature and brain metabolism in high grade subarachnoid hemorrhage patients.

    Science.gov (United States)

    Choi, H Alex; Ko, Sang-Bae; Chen, Huahiou; Gilmore, Emily; Carpenter, Amanda M; Lee, Danielle; Claassen, Jan; Mayer, Stephan A; Schmidt, J Michael; Lee, Kiwon; Connelly, E Sander; Paik, Myunghee; Badjatia, Neeraj

    2012-06-01

    Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH. This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined. Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

  5. The role of the endoplasmic reticulum stress response following cerebral ischemia.

    Science.gov (United States)

    Hadley, Gina; Neuhaus, Ain A; Couch, Yvonne; Beard, Daniel J; Adriaanse, Bryan A; Vekrellis, Kostas; DeLuca, Gabriele C; Papadakis, Michalis; Sutherland, Brad A; Buchan, Alastair M

    2017-01-01

    Background Cornu ammonis 3 (CA3) hippocampal neurons are resistant to global ischemia, whereas cornu ammonis (CA1) 1 neurons are vulnerable. Hamartin expression in CA3 neurons mediates this endogenous resistance via productive autophagy. Neurons lacking hamartin demonstrate exacerbated endoplasmic reticulum stress and increased cell death. We investigated endoplasmic reticulum stress responses in CA1 and CA3 regions following global cerebral ischemia, and whether pharmacological modulation of endoplasmic reticulum stress or autophagy altered neuronal viability . Methods In vivo: male Wistar rats underwent sham or 10 min of transient global cerebral ischemia. CA1 and CA3 areas were microdissected and endoplasmic reticulum stress protein expression quantified at 3 h and 12 h of reperfusion. In vitro: primary neuronal cultures (E18 Wistar rat embryos) were exposed to 2 h of oxygen and glucose deprivation or normoxia in the presence of an endoplasmic reticulum stress inducer (thapsigargin or tunicamycin), an endoplasmic reticulum stress inhibitor (salubrinal or 4-phenylbutyric acid), an autophagy inducer ([4'-(N-diethylamino) butyl]-2-chlorophenoxazine (10-NCP)) or autophagy inhibitor (3-methyladenine). Results In vivo, decreased endoplasmic reticulum stress protein expression (phospho-eIF2α and ATF4) was observed at 3 h of reperfusion in CA3 neurons following ischemia, and increased in CA1 neurons at 12 h of reperfusion. In vitro, endoplasmic reticulum stress inducers and high doses of the endoplasmic reticulum stress inhibitors also increased cell death. Both induction and inhibition of autophagy also increased cell death. Conclusion Endoplasmic reticulum stress is associated with neuronal cell death following ischemia. Neither reduction of endoplasmic reticulum stress nor induction of autophagy demonstrated neuroprotection in vitro, highlighting their complex role in neuronal biology following ischemia.

  6. Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

    Science.gov (United States)

    Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

    2017-10-01

    Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca(2+)) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca(2+) signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca(2+) sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca(2+)-release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca(2+) entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca(2+) signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca(2+) signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Cerebral haemodynamic response to acute intracranial hypertension induced by head-down tilt.

    Science.gov (United States)

    Bosone, Daniele; Ozturk, Vesile; Roatta, Silvestro; Cavallini, Anna; Tosi, Piera; Micieli, Giuseppe

    2004-01-01

    The aim of this study was to evaluate, in a context of general inhibition of the sympathetic nervous system, the cerebral haemodynamic response to -30 degrees head-down tilt (HDT), a manoeuvre that produces an increase in intracranial arterial pressure. Nineteen healthy subjects were studied according to the following protocol: 10 min lying in supine position, 10 min HDT, 10 min recovery. Inhibition of the sympathetic system was confirmed by the decrease in heart rate (-3.6 bpm) and arterial blood pressure (-5.9 mmHg, p<0.05) in the late phase of the test. Blood velocity and blood pusatility index initially increased (+3.2 cm s(-1) and +9% respectively, p<0.01) then returned towards baseline before the end of HDT, while the cerebrovascular resistance index (=arterial blood pressure/blood velocity) dropped significantly and remained below control level (-7%, p<0.01) throughout the test. The changes in both these indices were opposite to those reported in several sympathetic activation tests, such as the handgrip and cold pressor tests. Conversely, arterial pressure at cranial level increased during HDT (as it also does during sympathetic activation tests), due to the development of a hydrostatic pressure gradient between heart and brain levels. Therefore, the effects observed on the pulsatility and resistance indices are not secondary to the increase in intracranial arterial pressure. It is suggested that the changes in these cerebrovascular indices are mediated by a reduction of sympathetic tone that presumably involves the cerebral as well as the peripheral vascular bed.

  8. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

    DEFF Research Database (Denmark)

    Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin

    2016-01-01

    During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons ...... suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets....

  9. Cerebral metabolism in dogs assessed by (18)F-FDG PET: a pilot study to understand physiological changes in behavioral disorders in dogs.

    Science.gov (United States)

    Irimajiri, Mami; Miller, Michael A; Green, Mark A; Jaeger, Christine B; Luescher, Andrew U; Hutchins, Gary D

    2010-01-01

    The positron emission tomography (PET) imaging technique, which is utilized in human behavior and psychiatric disorder research, was performed on the brains of clinically normal mixed breed dogs, 3 hound-type (long floppy ears) mixed breed dogs and 3 non-hound retriever-type mixed breed dogs. Glucose metabolism was obtained with F-18 fluorodeoxyglucose (FDG), and quantitative analysis was performed by standardized uptake value (SUV) measurement. Magnetic resonance (MR) images were obtained in each dog, and these images were superimposed on PET images to identify anatomical locations. The glucose metabolism in each region of interest was compared between the three hound-type dogs and 3 non-hound-type dogs. The two anatomically different types of dog were compared to assess whether breed-typical behavioral tendencies (e.g., sniffing behavior in hound-type dogs, staring and retrieving in Labrador-type dogs) are reflected in baseline brain metabolic activity. There were no significant differences between the hound-type dogs and non-hound-type dogs in cerebral SUV values. These data might serve as normal canine cerebral metabolism data for FDG PET studies in dogs and form the basis for investigations into behavioral disorders in dogs such as compulsive disorder, anxiety disorders and cognitive dysfunction.

  10. Correlation between quantitative EEG and cerebral blood flow and oxygen metabolism in patients with dementia of Alzheimer type

    Energy Technology Data Exchange (ETDEWEB)

    Kudoh, Masako; Takahashi, Satoshi; Yonezawa, Hisashi [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1997-05-01

    Quantitative scalp EEG and cerebral blood flow (CBF) and oxygen metabolism (CMRO{sub 2}) measured by the steady-state {sup 15}O technique and positron emission tomography were studied in 19 patients with mild to moderate dementia of Alzheimer type (DAT) and age-matched controls (EEG=19, PET=6). Scalp electrodes were placed according to the international 10-20 method except for Cz, T3, and T4. To evaluate the relative changes in power for each frequency band between the two groups, the percentage power fraction (percentage power for each frequency band at a site compared to the total power at that site; %delta for 2.0-3.8 Hz, %theta for 4.0-7.8 Hz, %alpha for 8.0-12.8 Hz, %beta for 13.0-25.4 Hz) was calculated. Compared with controls, DAT patients showed a significant decrease in %alpha, while significant increases in %theta at all electrodes, and significant increases in %delta at the temporal, parietal and occipital electrodes were observed. The patient group displayed a significant decrease in rCBF and rCMRO{sub 2} in the parietal, temporal and frontal cortices, but the reduction in rCMRO{sub 2} was less remarkable than that of rCBF. %Theta at P3, O1 and O2 showed a significant negative correlation with rCBF, and %theta at P3, O1showed a significant negative correlation with rCMRO{sub 2}. %Delta at P3, P4 and T5 was significantly negatively correlated with rCBF in the corresponding regions, and %alpha at almost all the electrodes (except O1, F3, P3) was significantly positively correlated with rCBF in the corresponding regions. %Delta and %alpha did not show any significant correlation with rCMRO{sub 2}. (author)

  11. Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults.

    Science.gov (United States)

    Gardener, Samantha L; Sohrabi, Hamid R; Shen, Kai-Kai; Rainey-Smith, Stephanie R; Weinborn, Michael; Bates, Kristyn A; Shah, Tejal; Foster, Jonathan K; Lenzo, Nat; Salvado, Olivier; Laske, Christoph; Laws, Simon M; Taddei, Kevin; Verdile, Giuseppe; Martins, Ralph N

    2016-03-31

    Increasing evidence suggests that Alzheimer's disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18F]-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific

  12. Effect of postprandial hyperglycaemia in non-invasive measurement of cerebral metabolic rate of glucose in non-diabetic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro; Itoh, Harumi [Department of Radiology, Fukui Medical University, Matsuoka (Japan); Sadato, Norihiro; Nishizawa, Sadahiko; Yonekura, Yoshiharu [Biomedical Imaging Research Center, Fukui Medical University (Japan)

    2002-02-01

    The aim of this study was to determine the effect of postprandial hyperglycaemia (HG) on the non-invasive measurement of cerebral metabolic rate of glucose (CMRGlc). Five patients who had a meal within an hour before a fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) examination were recruited in this study. They underwent intermittent arterial blood sampling (measured input function), and, based on this sampling, CMRGlc was calculated using an autoradiographic method (CMRGlc{sub real}). Simulated input functions were generated based on standardised input function, body surface area and net injected dose of FDG, and simulated CMRGlc (CMRGlc{sub sim}) was also calculated. Percent error of the area under the curve (AUC) between measured (AUC{sub real}) and simulated input function (AUC{sub IFsim}) and percent error between CMRGlc{sub real} and CMRGlc{sub sim} were calculated. These values were compared with those obtained from a previous study conducted under fasting conditions (F). The serum glucose level in the HG group was significantly higher than that in the F group (165{+-}69 vs 100{+-}9 mg/dl, P=0.0007). Percent errors of AUC and CMRGlc in grey matter and white matter in HG were significantly higher than those in F (12.9%{+-}1.3% vs 3.5%{+-}2.2% in AUC, P=0.0015; 18.2%{+-}2.2% vs 2.9%{+-}1.9% in CMRGlc in grey matter, P=0.0028; 24.0%{+-}4.6% vs 3.4%{+-}2.2% in CMRGlc in white matter, P=0.0028). It is concluded that a non-invasive method of measuring CMRGlc should be applied only in non-diabetic subjects under fasting conditions. (orig.)

  13. Pair bond formation leads to a sustained increase in global cerebral glucose metabolism in monogamous male titi monkeys (Callicebus cupreus).

    Science.gov (United States)

    Maninger, Nicole; Hinde, Katie; Mendoza, Sally P; Mason, William A; Larke, Rebecca H; Ragen, Benjamin J; Jarcho, Michael R; Cherry, Simon R; Rowland, Douglas J; Ferrer, Emilio; Bales, Karen L

    2017-04-21

    Social bonds, especially attachment relationships, are crucial to our health and happiness. However, what we know about the neural substrates of these bonds is almost exclusively limited to rodent models and correlational experiments in humans. Here, we used socially monogamous non-human primates, titi monkeys (Callicebus cupreus) to experimentally examine changes in regional and global cerebral glucose metabolism (GCGM) during the formation and maintenance of pair bonds. Baseline positron emission tomography (PET) scans were taken of thirteen unpaired male titi monkeys. Seven males were then experimentally paired with females, scanned and compared, after one week, to six age-matched control males. Five of the six control males were then also paired and scanned after one week. Scans were repeated on all males after four months of pairing. PET scans were coregistered with structural magnetic resonance imaging (MRI), and region of interest (ROI) analysis was carried out. A primary finding was that paired males showed a significant increase in [18F]-fluorodeoxyglucose (FDG) uptake in whole brain following one week of pairing, which is maintained out to four months. Dopaminergic, "motivational" areas and those involved in social behavior showed the greatest change in glucose uptake. In contrast, control areas changed only marginally more than GCGM. These findings confirm the large effects of social bonds on GCGM. They also suggest that more studies should examine how social manipulations affect whole-brain FDG uptake, as opposed to assuming that it does not change across condition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion

    Science.gov (United States)

    Reimer, Michell Mario; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Holland, Philip Robert; Smith, Jessica; Gliddon, Catherine; Wood, Emma R; Herzyk, Pawel; Brophy, Peter; McCulloch, James; Horsburgh, Karen

    2015-01-01

    Myelinated axons have a distinct protein architecture which is essential for action potential propagation, neuronal communication and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, is suggested to contribute to age-related cognitive decline. We sought to determine whether there are selective and early alterations in the protein architecture of myelinated axons in response to cerebral hypoperfusion. Using a mouse model of hypoperfusion we assessed changes in proteins, by confocal laser scanning microscopy, critical to the maintenance of the paranodes (contactin-associated protein (CASPR); Neurofascin155 (Nfasc155)), the nodes of Ranvier (voltage-gated sodium channels (Nav1.6), Neurofascin186 (Nfasc186) and AnkyrinG), axon-glial integrity (myelin-associated glycoprotein (MAG)), axon (SMI312) and myelin (myelin basic protein (MBP)). As early as 3 days after hypoperfusion, the paranodal septate-like junctions were damaged. This was marked by a progressive reduction of paranodal Neurofascin signal and a loss of septate-like junctions confirmed by electron microscopy. Concurrent with paranodal disruption there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Nfasc186 were unchanged and there were no changes in axonal and myelin integrity with hypoperfusion. Disruption of axon-glial integrity was also determined after hypoperfusion by changes in the spatial distribution of MAG staining. These nodal/paranodal changes were more pronounced after one month of hypoperfusion. A microarray analysis of white matter enriched samples of sham as compared with hypoperfused mice indicated that there were significant alterations in 129 genes (p<0.001). Subsequent enrichment analysis indicated alterations in biological pathways including inflammatory response, cytokine-cytokine receptor interaction, blood vessel development and cell

  15. Metabolic responses to ethanol and butanol in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Jiang, Yongguang; Xiao, Peng; Shao, Qing; Qin, Huan; Hu, Zhangli; Lei, Anping; Wang, Jiangxin

    2017-01-01

    Microalgae have been demonstrated to be among the most promising phototrophic species for producing renewable biofuels and chemicals. Ethanol and butanol are clean energy sources with good chemical and physical properties as alternatives to gasoline. However, biosynthesis of these two biofuels has not been achieved due to low tolerance of algal cells to ethanol or butanol. With an eye to circumventing these problems in the future and engineering the robust alcohol-producing microalgal hosts, we investigated the metabolic responses of the model green alga Chlamydomonas reinhardtii to ethanol and butanol. Using a quantitative proteomics approach with iTRAQ-LC-MS/MS technologies, we detected the levels of 3077 proteins; 827 and 730 of which were differentially regulated by ethanol and butanol, respectively, at three time points. In particular, 41 and 59 proteins were consistently regulated during at least two sampling times. Multiple metabolic processes were affected by ethanol or butanol, and various stress-related proteins, transporters, cytoskeletal proteins, and regulators were induced as the major protection mechanisms against toxicity of the organic solvents. The most highly upregulated butanol response protein was Cre.770 peroxidase. The study is the first comprehensive view of the metabolic mechanisms employed by C. reinhardtii to defend against ethanol or butanol toxicity. Moreover, the proteomic analysis provides a resource for investigating potential gene targets for engineering microalgae to achieve efficient biofuel production.

  16. Regional cerebral blood flow and metabolism in patients with transient global amnesia. A study using SPECT and {sup 1}H-MRS

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Tetsuya; Hirata, Koichi; Tatsumoto, Muneto; Yamazaki, Kaoru [Dokkyo Univ., Tochigi (Japan). School of Medicine; Sato, Toshihiko

    1997-06-01

    In 13 patients with transient global amnesia (TGA), we studied the clinical course and changes over time by means of imaging techniques such as SPECT. MRI, and proton MR spectroscopy ({sup 1}H-MRS). In the case of SPECT, a cerebral blood flow decrease at the time center of the temporal lobe persisted at least for more than one month. In many patients, no abnormal signs were found on MRI. Despite the presence of intracranial impairment of energy metabolism, no evidence of cerebral ischemia was obtained using {sup 1}H-MRS at the acute and subacute stages. There were thus discrepancies between the symptoms and the findings of SPECT as well as the findings of {sup 1}H-MRS. These data suggest that TGA may not necessarily be caused by cerebra1 ischemia. (author)

  17. Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates

    DEFF Research Database (Denmark)

    McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B

    2017-01-01

    comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design. Cerebral cortical and hippocampal slices...... prepared from 16 to 18-week-old mice were incubated for 15-90 min with unlabeled glucose in combination with [U-(13)C]glucose or [1,2-(13)C]acetate. Our newly developed incubation apparatus allows accurate control of temperature and is designed to avoid evaporation of the incubation medium. Subsequent...... to incubation, slices were extracted and extracts analyzed for (13)C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography-mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation...

  18. Anterior cerebral blood velocity and end-tidal CO2 responses to exercise differ in children and adults.

    Science.gov (United States)

    Ellis, Lindsay A; Ainslie, Philip N; Armstrong, Victoria A; Morris, Laura E; Simair, Ryan G; Sletten, Nathan R; Tallon, Christine M; McManus, Ali M

    2017-06-01

    Little is known about the response of the cerebrovasculature to acute exercise in children and how these responses might differ with adults. Therefore, we compared changes in middle cerebral artery blood velocity (MCAVmean), end-tidal Pco2 ([Formula: see text]), blood pressure, and minute ventilation (V̇e) in response to incremental exercise between children and adults. Thirteen children [age: 9 ± 1 (SD) yr] and thirteen sex-matched adults (age: 25 ± 4 yr) completed a maximal exercise test, during which MCAVmean, [Formula: see text], and V̇e were measured continuously. These variables were measured at rest, at exercise intensities specific to individual ventilatory thresholds, and at maximum. Although MCAVmean was higher at rest in children compared with adults, there were smaller increases in children (1-12%) compared with adults (12-25%) at all exercise intensities. There were alterations in [Formula: see text] with exercise intensity in an age-dependent manner [F(2.5,54.5) = 7.983, P 0.05) until hyperventilation-induced reductions following the respiratory compensation point. In adults, [Formula: see text] increased with exercise intensity (36-45 mmHg, P adults showed a greater hyperventilation-induced hypocapnia than children. These findings show that the relative increase in MCAVmean during exercise was attenuated in children compared with adults. There was also a weaker relationship between MCAVmean and [Formula: see text] during exercise in children, suggesting that cerebral perfusion may be regulated by different mechanisms during exercise in the child.NEW & NOTEWORTHY These findings provide the first direct evidence that exercise increases cerebral blood flow in children to a lesser extent than in adults. Changes in end-tidal CO2 parallel changes in cerebral perfusion in adults but not in children, suggesting age-dependent regulatory mechanisms of cerebral blood flow during exercise. Copyright © 2017 the American Physiological Society.

  19. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  20. Thermal sensation and thermophysiological responses with metabolic step-changes

    DEFF Research Database (Denmark)

    Goto, Tomonobu; Toftum, Jørn; deDear, Richard

    2006-01-01

    This study investigated the effect on thermal perception and thermophysiological variables of controlled metabolic excursions of various intensities and durations. Twenty-four subjects alternately were seated on a chair or exercised by walking on a treadmill at a temperature predicted to be neutral...... at sedentary activity. In a second experimental series, subjects alternated between rest and exercise as well as between exercise at different intensities at two temperature levels. Measurements comprised skin and oesophageal temperatures, heart rate and subjective responses. Thermal sensation started to rise....... The sensitivity of thermal sensation to changes in core temperature was higher for activity down-steps than for up-steps. A model was proposed that estimates transient thermal sensation after metabolic step-changes. Based on predictions by the model, weighting factors were suggested to estimate a representative...

  1. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    Directory of Open Access Journals (Sweden)

    Chandra Prakash

    2015-12-01

    Full Text Available Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs, and transport proteins coordinate drug influx (phase 0 and drug/drug-metabolite efflux (phase III. Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs, i.e. PXR (pregnane X receptor and CAR (constitutive androstane receptor, and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR, due to transactivation of xenobiotic-response elements (XREs present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug's impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse

  2. Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stadlbauer, Andreas, E-mail: andi@nmr.at [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany); Department of Radiology and Nuclear Medicine, Medical University Vienna, Währinger Gürtel 18-20, A-1097 Vienna (Austria); Pichler, Petra [First Department of Internal Medicine, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Poelten (Austria); Karl, Marianne [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Brandner, Sebastian [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen (Germany); Lerch, Claudia [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria); Renner, Bertold [Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen (Germany); Heinz, Gertraud [Institute of Medical Radiology, University Clinic of St. Pölten, Propst Führer-Straße 4, A-3100 St. Pölten (Austria)

    2015-06-15

    Highlights: • Antiangiogenic therapy can lead to a decreased in CBV in normal brain tissue. • Responding and pseudoresponding lesions to AAT showed a similar CBV decrease. • Cho and NAA allowed for a distinction of responding and pseudoresponding lesions. • Cr ratios are not suited for evaluation of antiangiogenic therapy response. • Responders to AAT may have an increased risk for remote progression of the GBM. - Abstract: Objectives: To evaluate the usefulness of quantitative advanced magnetic resonance imaging (MRI) methods for assessment of antiangiogenic therapy (AAT) response in recurrent glioblastoma multiforme (GBM). Methods: Eighteen patients with recurrent GBM received bevacizumab and 18 patients served as control group. Baseline MRI and two follow-up examinations were acquired every 3–5 months using dynamic susceptibility-weighted contrast (DSC) perfusion MRI and {sup 1}H-MR spectroscopic imaging ({sup 1}H-MRSI). Maps of absolute cerebral blood volume (aCBV) were coregistered with choline (Cho) and N-acetyl-aspartate (NAA) concentrations and compared to usually used relative parameters as well as controls. Results: Perfusion significantly decreased in responding and pseudoresponding GBMs but also in normal appearing brain after AAT onset. Cho and NAA concentrations were superior to Cr-ratios in lesion differentiation and showed a clear gap between responding and pseudoresponding lesions. Responders to AAT exceptionally frequently (6 out of 8 patients) showed remote GBM progression. Conclusions: Quantification of CBV reveals changes in normal brain perfusion due to AAT, which were not described so far. DSC perfusion MRI seems not to be suitable for differentiation between response and pseudoresponse to AAT. However, absolute quantification of brain metabolites may allow for distinction due to a clear gap at 6–9 months after therapy onset.

  3. Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Richter, E; Madsbad, S

    1987-01-01

    . To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...... with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients...

  4. Effect of radiographic contrast agents on leukocyte metabolic response

    Energy Technology Data Exchange (ETDEWEB)

    Hernanz-Schulman, M. [Dept. of Pediatric Radiology, Vanderbilt Children' s Hospital, Nashville, TN (United States); Vanholder, R.; Waterloos, M.A. [Dept. of Internal Medicine, Nephrology Section, University Hospital, Gent (Belgium); Hakim, R.; Schulman, G. [Department of Nephrology, Vanderbilt University Medical Center, Nashville, TN (United States)

    2000-06-01

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significat activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these dsata serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  5. Bone marrow stromal cell transplantation enhances recovery of local glucose metabolism after cerebral infarction in rats: a serial 18F-FDG PET study.

    Science.gov (United States)

    Miyamoto, Michiyuki; Kuroda, Satoshi; Zhao, Songji; Magota, Keiichi; Shichinohe, Hideo; Houkin, Kiyohiro; Kuge, Yuji; Tamaki, Nagara

    2013-01-01

    This study aimed to assess whether (18)F-FDG PET could serially monitor the beneficial effects of bone marrow stromal cells (BMSC) on cerebral glucose metabolism when transplanted into the infarct brain of rats. The BMSC from green fluorescent protein transgenic rats or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 d after permanent middle cerebral artery occlusion of rats. Local glucose metabolism was semiquantitatively measured at 6 and 35 d after ischemia using (18)F-FDG PET. Motor function was serially evaluated throughout the experiments. At 35 d after ischemia, immunohistochemistry was performed to evaluate the phenotype of BMSC and their effects on the expression of brain-type glucose transporters. BMSC transplantation not only enhanced functional recovery but also promoted the recovery of glucose utilization in the periinfarct area when stereotactically transplanted at 1 wk after ischemia. The engrafted cells were widely distributed, and most expressed a neuron-specific protein, NeuN. BMSC transplantation also prevented the pathologic upregulation of glucose transporters in the periinfarct neocortex. The present findings strongly suggest that the BMSC may enhance functional recovery by promoting the recovery of local glucose metabolism in the periinfarct area when directly transplanted into the infarct brain at clinically relevant timing. The BMSC also inhibit the pathologic upregulation of brain-isoform glucose transporters type 1 and 3. (18)F-FDG PET may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situations.

  6. Metabolomics reveals insect metabolic responses associated with fungal infection.

    Science.gov (United States)

    Xu, Yong-Jiang; Luo, Feifei; Gao, Qiang; Shang, Yanfang; Wang, Chengshu

    2015-06-01

    The interactions between insects and pathogenic fungi are complex. We employed metabolomic techniques to profile insect metabolic dynamics upon infection by the pathogenic fungus Beauveria bassiana. Silkworm larvae were infected with fungal spores and microscopic observations demonstrated that the exhaustion of insect hemocytes was coupled with fungal propagation in the insect body cavity. Metabolomic analyses revealed that fungal infection could significantly alter insect energy and nutrient metabolisms as well as the immune defense responses, including the upregulation of carbohydrates, amino acids, fatty acids, and lipids, but the downregulation of eicosanoids and amines. The insect antifeedant effect of the fungal infection was evident with the reduced level of maclurin (a component of mulberry leaves) in infected insects but elevated accumulations in control insects. Insecticidal and cytotoxic mycotoxins like oosporein and beauveriolides were also detected in insects at the later stages of infection. Taken together, the metabolomics data suggest that insect immune responses are energy-cost reactions and the strategies of nutrient deprivation, inhibition of host immune responses, and toxin production would be jointly employed by the fungus to kill insects. The data obtained in this study will facilitate future functional studies of genes and pathways associated with insect-fungus interactions.

  7. Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study

    Energy Technology Data Exchange (ETDEWEB)

    Drzezga, Alexander; Willoch, Frode; Schwaiger, Markus [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675, Muenchen (Germany); Lautenschlager, Nicola; Riemenschneider, Matthias; Kurz, Alexander [Department of Psychiatry and Psychotherapy, Technische Universitaet Muenchen, Muenchen (Germany); Siebner, Hartwig [Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London (United Kingdom); Minoshima, Satoshi [Department of Radiology, University of Washington, Seattle, WA (United States)

    2003-08-01

    A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.8{+-}5.8 years); these examinations included neuropsychological testing, structural cranial magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography (PET) evaluation of relative cerebral glucose metabolic rate (rCMRglc). Individual PET scans were stereotactically normalised with NEUROSTAT software (Univ. of Michigan, Ann Arbor, USA). Subsequently, statistical comparison of PET data with an age-matched healthy control population and between patient subgroups was performed using SPM 99 (Wellcome Dept. of Neuroimaging Sciences, London, UK). After 1 year, eight patients (36%) had developed probable AD (referred to as MCI{sub AD}), whereas 12 (55%) were still classified as having stable MCI (referred to as MCI{sub MCI}). Compared with the healthy control group, a reduced rCMRglc in AD-typical regions, including the temporoparietal and posterior cingulate cortex, was detected at baseline in patients with MCI{sub AD}. Abnormalities in the posterior cingulate cortex reached significance even in comparison with the MCI{sub MCI} group. After 1 year, MCI{sub AD} patients demonstrated an additional bilateral reduction of rCMRglc in prefrontal areas, along with a further progression of the abnormalities in the parietal and posterior cingulate cortex. No such changes were observed in the MCI{sub MCI} group. In patients with MCI, characteristic cerebral metabolic differences can be delineated at the time of initial presentation, which helps to define prognostic subgroups. A newly emerging reduction

  8. Mechanical, Metabolic and Perceptual Response during Sprint Training.

    Science.gov (United States)

    Jimenez-Reyes, P; Pareja-Blanco, F; Cuadrado-Peñafiel, V; Morcillo, J A; Párraga, J A; González-Badillo, J J

    2016-09-01

    This study aimed to analyze perceptual, metabolic and mechanical responses to sprint training sessions. 9 male high-level sprinters performed 40 m running sprints up to a loss of 3% in speed, with 4 min rests between sets. Perceptual (rating of perceived exertion, RPE), mechanical (speed and countermovement jump height loss) and metabolic (blood lactate and ammonia) parameters were measured pre-exercise and after each sprint was performed. Relationships between the variables were calculated with a 90% confidence interval. Jump height loss showed almost perfect relationships with both blood lactate (r=0.96 (0.95 to 0.97)) and ammonia (r=0.95 (0.94 to 0.95)), whereas speed loss, number of sprints performed and RPE values showed large-very large relationships with blood lactate and ammonia. Furthermore, an almost perfect curvilinear relationship was observed between lactate and ammonia concentrations (R(2)=0.96 (0.95 to 0.97)). These results suggest that countermovement jump (CMJ) height can be used to quantify the fatigue induced during a typical sprint training session, and may prove a useful tool to facilitate individualized load monitoring. The results indicate that the CMJ is a better monitor of metabolic fatigue than traditional measures. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (Pcitric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  10. Regional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease.

    Science.gov (United States)

    Hanyu, Haruo; Shimizu, Takeshi; Tanaka, Yuriko; Takasaki, Masaru; Koizumi, Kiyoshi; Abe, Kimihiko

    2003-01-01

    We attempted to identify the characteristic patterns in regional cerebral blood flow (rCBF) of patients with Alzheimer's disease who responded to donepezil therapy. Sixty-one patients treated with donepezil were divided into two groups (responders and nonresponders) on the basis of changes in their Mini Mental State Examination (MMSE) scores from baseline to study endpoint. We analyzed single-photon emission computed tomography data (SPECT) at baseline using three-dimensional stereotactic surface projections and compared differences in rCBF between the two groups. Statistical maps showed a significantly lower rCBF of the lateral and medial frontal lobes in the nonresponders than in the responders. There was a significant inverse correlation between the relative rCBF reduction in the frontal lobe and the MMSE change. These results suggest that frontal function, as assessed by SPECT, affects the patient's response to treatment with donepezil. Measuring rCBF may aid in the selection of possible treatment responders. Copyright 2003 S. Karger AG, Basel

  11. Polymorphisms in inflammatory and immune response genes associated with cerebral cavernous malformation type 1 severity

    Science.gov (United States)

    Choquet, Hélène; Pawlikowska, Ludmila; Nelson, Jeffrey; McCulloch, Charles E.; Akers, Amy; Baca, Beth; Khan, Yasir; Hart, Blaine; Morrison, Leslie; Kim, Helen

    2014-01-01

    Background Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by mutations in the Krev Interaction Trapped 1 (KRIT1/CCM1) gene, and characterized by multiple brain lesions that often result in intracerebral hemorrhage (ICH), seizures, and neurological deficits. Carriers of the same genetic mutation can present with variable symptoms and severity of disease, suggesting the influence of modifier factors. Evidence is emerging that inflammation and immune response play a role in the pathogenesis of CCM. The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence the severity of familial CCM1 disease, as manifested by ICH and greater brain lesion count. Methods Hispanic CCM1 patients (n=188) harboring the founder Q455X ‘common Hispanic mutation’ (CHM) in the KRIT1 gene were analyzed at baseline. Participants were enrolled between June 2010 and March 2014 either through the Brain Vascular Malformation Consortium (BVMC) study or through the Angioma Alliance organization. Clinical assessment and cerebral susceptibility-weighted magnetic resonance imaging were performed to determine ICH as well as total and large (≥5 mm in diameter) lesion counts. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We analyzed 830 variants in 56 inflammatory and immune response genes for association with ICH and residuals of log-transformed total or large lesion count adjusted for age at enrollment and gender. Variants were analyzed individually, grouped by sub-pathways or whole pathway. Results At baseline, 30.3% of CCM1-CHM subjects had ICH, with a mean ± standard deviation (SD) of 60.1 ± 115.0 (range 0 to 713) for total lesions and 4.9 ± 8.7 (range 0 to 104) for large lesions. The heritability estimates explained by all autosomal variants were 0.20 (SE=0.31), 0.81 (SE=0.17) and 0.48 (SE=0.19), for ICH, total lesion count and large lesion count

  12. Cerebral autoregulation in response to posture change in elderly subjects-assessment by wavelet phase coherence analysis of cerebral tissue oxyhemoglobin concentrations and arterial blood pressure signals.

    Science.gov (United States)

    Gao, Yuanjin; Zhang, Ming; Han, Qingyu; Li, Wenhao; Xin, Qing; Wang, Yan; Li, Zengyong

    2015-02-01

    This study aims to assess the dynamic cerebral autoregulation (dCA) in response to posture change using wavelet phase coherence (WPCO) of cerebral tissue oxyhemoglobin concentrations (Delta [HbO2]) and arterial blood pressure (ABP) signals in healthy elderly subjects. Continuous recordings of near-infrared spectroscopy (NIRS) and ABP signals were obtained from simultaneous measurements in 16 healthy elderly subjects (age: 68.9±7.1 years) and 19 young subjects (age: 24.9±3.2 years). The phase coherence between Delta [HbO2] and ABP oscillations in six frequency intervals (I, 0.6-2 Hz; II, 0.15-0.6 Hz; III, 0.05-0.15 Hz; IV, 0.02-0.05 Hz, V, 0.0095-0.02 Hz and VI, 0.005-0.0095 Hz) was analyzed using WPCO. The sit-to-stand posture change induces significantly lower WPCO in interval III (F=5.50 p=0.025) in the elderly subjects than in the young subjects. However, the stand-to-sit posture change induces higher WPCO in intervals II (F=5.25 p=0.028) and V (F=6.22 p=0.018) in the elderly subjects than in the young subjects. The difference of WPCO in response to posture change between the elderly and the young subjects indicates an altered CA due to aging. This study provides new insight into the dynamics of CA and may be useful in identifying the risk for dCA processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Liposoluble vitamins in Crustacean feed: Metabolic and Histological responses.

    Science.gov (United States)

    Fernández-Gimenez, Analía Verónica

    2016-05-01

    Vitamins are vital for normal growth and survival of living organisms and they are distributed in feedstuffs in small quantities. This review is focused on the liposoluble vitamins (A, D, E and K) in the diets and metabolic responses of the Argentine penaeoid shrimps Pleoticus muelleri and Artemesia longinaris, distributed along the South American coast line. Growth, survival and histological analyses serve as indicators of the nutritional value derived from vitamin deficiency. Liposoluble vitamins are also related to stress, antioxidant defense and immune response of shrimps. Effective diet for shrimp culture that provide not only macronutrients including protein and lipid but also micronutrients such as vitamins for optimal growth is an ever improving subject. This review may help formulating suitable feeds for shrimps.

  14. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

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    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  15. Reduction of Experimental Cerebral Malaria and Its Related Proinflammatory Responses by the Novel Liposome-Based β-Methasone Nanodrug

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    Jintao Guo

    2014-01-01

    Full Text Available Cerebral malaria (CM is a severe complication of and a leading cause of death due to Plasmodium falciparum infection. CM is likely the result of interrelated events, including mechanical obstruction due to parasite sequestration in the microvasculature, and upregulation of Th1 immune responses. In parallel, blood-brain-barrier (BBB breakdown and damage or death of microglia, astrocytes, and neurons occurs. We found that a novel formulation of a liposome-encapsulated glucocorticosteroid, β-methasone hemisuccinate (nSSL-BMS, prevents experimental cerebral malaria (ECM in a murine model and creates a survival time-window, enabling administration of an antiplasmodial drug before severe anemia develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation, expressed by altered levels of corresponding cytokines and chemokines. The results indicate the role of integrated immune responses in ECM induction and show that the new steroidal nanodrug nSSL-BMS reverses the balance between the Th1 and Th2 responses in malaria-infected mice so that the proinflammatory processes leading to ECM are prevented. Overall, because of the immunopathological nature of CM, combined immunomodulator/antiplasmodial treatment should be considered for prevention/treatment of human CM and long-term cognitive damage.

  16. Novelty Seeking, Harm Avoidance, and Cerebral Responses to Conflict Anticipation: An Exploratory Study.

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    Hu, Jianping; Hu, Sien; Maisano, Julianna R; Chao, Herta H; Zhang, Sheng; Li, Chiang-Shan R

    2016-01-01

    Proactive control allows us to maneuver a changing environment and individuals are distinct in how they anticipate and approach such changes. Here, we examined how individual differences in personality traits influence cerebral responses to conflict anticipation, a critical process of proactive control. We explored this issue in an fMRI study of the stop signal task, in which the probability of stop signal - p(Stop) - was computed trial by trial with a Bayesian model. Higher p(Stop) is associated with prolonged go trial reaction time, indicating conflict anticipation and proactive control of motor response. Regional brain activations to conflict anticipation were correlated to novelty seeking (NS), harm avoidance (HA), reward dependence, as assessed by the Tridimensional Personality Questionnaire, with age and gender as covariates, in a whole-brain linear regression. Results showed that increased anticipation of the stop signal is associated with activations in the bilateral inferior parietal lobules (IPL), right lateral orbitofrontal cortex (lOFC), middle frontal gyrus (MFG), anterior pre-supplementary motor area (pre-SMA), and bilateral thalamus, with men showing greater activation in the IPL than women. NS correlated negatively to activity in the anterior pre-SMA, right IPL, and MFG/lOFC, and HA correlated negatively to activity in the thalamus during conflict anticipation. In addition, the negative association between NS and MFG/lOFC activity was significant in men but not in women. Thus, NS and HA traits are associated with reduced mobilization of cognitive control circuits when enhanced behavioral control is necessary. The findings from this exploratory study characterize the influence of NS and HA on proactive control and provide preliminary evidence for gender differences in these associations.

  17. Novelty seeking, harm avoidance, and cerebral responses to conflict anticipation: An exploratory study

    Directory of Open Access Journals (Sweden)

    Jianping Hu

    2016-11-01

    Full Text Available Proactive control allows us to maneuver a changing environment and individuals are distinct in how they anticipate and approach such changes. Here, we examined how individual differences in personality traits influence cerebral responses to conflict anticipation, a critical process of proactive control. We explored this issue in an fMRI study of the stop signal task, in which the probability of stop signal – p(Stop – was computed trial by trial with a Bayesian model. Higher p(Stop is associated with prolonged go trial reaction time, indicating conflict anticipation and proactive control of motor response. Regional brain activations to conflict anticipation were correlated to novelty seeking (NS, harm avoidance (HA, reward dependence (RD, as assessed by the Tridimensional Personality Questionnaire, with age and gender as covariates, in a whole-brain linear regression. Results showed that increased anticipation of the stop signal is associated with activations in the bilateral inferior parietal lobules (IPL, right lateral orbitofrontal cortex (lOFC, middle frontal gyrus (MFG, anterior pre-supplementary motor area (pre-SMA, and bilateral thalamus, with men showing greater activation in the IPL than women. NS correlated negatively to activity in the anterior pre-SMA, right IPL, and MFG/lOFC, and HA correlated negatively to activity in the thalamus during conflict anticipation. In addition, the negative association between NS and MFG/lOFC activity was significant in men but not in women. Thus, NS and HA traits are associated with reduced mobilization of cognitive control circuits when enhanced behavioral control is necessary. These findings from this exploratory study characterize the influence of NS and HA on proactive control and provide preliminary evidence for gender differences in these associations.

  18. Significance of the presence of metabolic syndrome in patients with asymptomatic arteriosclerosis affecting the aorta and the cerebral, extra-cranial carotid and coronary arteries.

    Science.gov (United States)

    Ohnuki, Tomohide; Takahashi, Wakoh; Ohnuki, Youichi; Kawada, Shiaki; Takizawa, Shunya

    2013-01-01

    The presence of metabolic syndrome (MetS) is strongly associated with stroke and cardiovascular diseases. However, the relationship between MetS and the localization of atherosclerosis at various sites remains uncertain. In this study, in order to reveal the relevance of MetS to atherosclerosis at several sites, we investigated the relationships among vascular risk factors, asymptomatic cerebral infarction and atherosclerosis in the aorta and carotid and coronary arteries in adults without overtly symptomatic cerebrovascular or cardiovascular disease. The subjects in this study included 2,759 Japanese participants (1,845 men and 914 women, mean age: 52 years) with no history of stroke or cardiovascular events. The diagnosis of MetS was made based on modifications to criteria obtained from the National Cholesterol Education Program Adult Treatment Panel. In all subjects, the presence of cerebral infarction in the extra-cranial carotid, coronary and aortic arteries was investigated using MRI, B-mode ultrasonography and CT. Of the 2,759 subjects, 796 (28.9%) fulfilled the criteria for MetS. The presence of MetS increased the odds ratio (OR) to 1.89 (95% confidence interval (CI): 1.35-2.65, p-value arteriosclerosis, 2.07 (95% CI: 1.62-2.27, p-value arteriosclerosis in all regions, including the cerebral small-vessels, extra-cranial carotid arteries, coronary arteries and abdominal aorta. MetS might be a predictor for small and large vessel disease throughout the body.

  19. Evaluation of cerebral metabolism in patients with unilateral carotid stenosis by proton MR spectroscopy: a correlative study with cerebral hemodynamics by acetazolamide stress brain perfusion SPECT (acz-SPECT)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Seung; Kim, Geun Eun; Lee, Jeong Hee; Kim, Do Gyun; Kim, Sang Tae; Lee, Hee Kyung [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of)

    2001-07-01

    Carotid stenosis may lead not only to cerebral hemodynamic compromise but also cerebral metabolic changes without overt infarction. To investigate the brain metabolic changes as a result of hemodynamic compromise in pts with carotid stenosis, we compared the changes in metabolism of the gray and white matter detected by proton MRS with cortical hemodynamics measured by Acz-SPECT. We prospectively studied symptomatic 18 pts (M/F=15/3, mean ages: 64.4y) with unilateral carotid stenosis. All pts underwent Acz-SPECT and MRS with 3 days. rCBF and rCVR of MCA territory were assessed by Acz-SPECT. Hemodynamic compromise was graded as stage 0 (normal rCBF and rCVR), stage 1 (normal rCBF and reduced rCVR), and stage 2( reduced rCBF and rCVR). Brain metabolism was assessed by measuring the peaks of N-acetyl aspartate (NAA), choline (Cho), and the sum of creatine and phosphocreatine (Cr) from noninfarcted white matter in the both centrum semiovales and gray matter in both MCA territories. On Acz-SPECT, 7 pts showed stage 2 were significantly lower than in pts with stage 0 (p<0.01). The asymmetric ratio of NAA/Cr in pts with state 2 was also significantly lower than in pts with stage 1(p<0.05). The asymmetric ratio of Cho/Cr was increased as hemodynamic stage increased but the differences were not statistically significant among 3 stages. In cortical gray matter, the asymmetric ratios of NAA/Cho and NAA/Cr were decreased statistically significant among 3 stages. In cortical gray matter, the asymmetric ratios of NAA/Cho and NAA/Cr were decreased and that of Cho/Cr was increased as hemodynamic stage increased. However, these differences were not statistically significant among 3 stages. The asymmetric ratios of NAA/Cho of centrum semiovale in pts with reduced rCBF and/or reduced rCVR were lower than in pts with normal perfusion. Our results indicate the metabolic changes detected by proton MRS in patients with carotid stenosis reflect a hemodynamic compromised state.

  20. Maximal aerobic and anaerobic exercise responses in children with cerebral palsy.

    Science.gov (United States)

    Balemans, Astrid C J; Van Wely, Leontien; De Heer, Susan J A; Van den Brink, Janneke; De Koning, Jos J; Becher, Jules G; Dallmeijer, Annet J

    2013-03-01

    The objective of this study is to compare the maximal aerobic and anaerobic exercise responses of children with cerebral palsy (CP) by level of motor impairment and in comparison with those of typically developing children (TD). Seventy children with CP, with varying levels of motor impairment (Gross Motor Function Classification System (GMFCS) I-III), and 31 TD performed an incremental continuous maximal aerobic exercise test and a 20-s anaerobic Wingate test on a cycle ergometer. Peak oxygen uptake (V˙O2peak), anaerobic threshold (AT), peak ventilation (V˙Epeak), peak oxygen pulse (peak O2 pulse), peak ventilatory equivalent of oxygen (peak V˙E/V˙O2) and carbon dioxide (peak V˙E/V˙CO2), peak aerobic power output (POpeak), and mean anaerobic power (P20mean) were measured. Isometric leg muscle strength was determined as a secondary outcome. Analysis revealed a lower V˙O2peak for CP (I: 35.5 ± 1.2 (SE); II: 33.9 ± 1.6; III: 29.3 ± 2.5 mL·kg-1·min-1) compared with TD (41.0 ± 1.3, P V˙Epeak and peak O2 pulse were also lower, whereas peak V˙E/V˙CO2 was higher in CP compared with TD (P V˙E/V˙O2 similar between groups. All these variables showed no differences for different motor impairment levels. POpeak was lower for CP (I: 2.4 ± 0.1; II: 1.8 ± 0.1; III: 1.4 ± 0.2 W·kg-1) versus TD (3.0 ± 0.1, P CP (I: 4.6 ± 0.2; II: 3.3 ± 0.2; III: 2.5 ± 0.4 W·kg-1) versus TD (6.4 ± 0.2, P CP have decreased aerobic and anaerobic exercise responses, but decreases in respiratory and aerobic exercise responses were not as severe as predicted by motor impairment. Future research should reveal the role of inactivity on the exercise responses of children with CP and possibilities for improvement through training interventions.

  1. In Vivo Quantification of Cerebral R2FNx01-Response to Graded Hyperoxia at 3 Tesla

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    Grigorios Gotzamanis

    2015-01-01

    Full Text Available Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2FNx01 of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO 2 , and heart pulse rate were monitored during the challenge. R2FNx01 maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI data, acquired at 3.0T. The average values in the segmented white matter (WM and gray matter (GM were tested by the analysis of variance (ANOVA, with Bonferroni post-hoc correction. The GM R2FNx01-reactivity to hyperoxia was modeled using the Hill′s equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05 decrease of the R2FNx01 in GM. Under normoxia the GM-R2FNx01 was 17.2 ± 1.1 s -1 . At 75% O 2 supply, the R2FNx01 had reached a saturation level, with 16.4 ± 0.7 s -1 (P = 0.02, without a significant further decrease for 100% O 2 . The R2FNx01-response of GM correlated positively with CO 2 partial pressure (R = 0.69 ± 0.19 and negatively with SaO 2 (R = -0.74 ± 0.17. The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055. The Hill′s model predicted a maximum R2FNx01 response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2FNx01 responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2FNx01-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.

  2. Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer`s type and vascular dementia with deep white matter changes

    Energy Technology Data Exchange (ETDEWEB)

    Tohgi, H.; Yonezawa, H.; Takahashi, S.; Sato, N.; Kato, E.; Kudo, M. [Department of Neurology, Iwate Medical University (Japan); Hatano, K.; Sasaki, T. [Nishina Memorial Cyclotron Centre (Japan Radioisotope Association) and Cyclotron Research Centre, Iwate Medical University, Morioka (Japan)

    1998-03-01

    Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO{sub 2}), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer`s type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO{sub 2} and rCBV were determined using C{sup 15}O{sub 2}, {sup 15}O{sub 2} and C{sup 15}O, respectively. rCBF and CMRO{sub 2} were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO{sub 2} was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. (orig.) With 3 figs., 2 tabs., 32 refs.

  3. Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males.

    Science.gov (United States)

    Mikkelsen, Kristian H; Seifert, Thomas; Secher, Niels H; Grøndal, Thomas; van Hall, Gerrit

    2015-02-01

    Ketone bodies are substrates during fasting and when on a ketogenic diet not the least for the brain and implicated in the management of epileptic seizures and dementia. Moreover, D-β-hydroxybutyrate (HOB) is suggested to reduce blood glucose and fatty acid levels. The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism. Single trial. Hospital. Healthy post-absorptive males (n = 6). Subjects were studied under basal condition and three consecutive 1-hour periods with a 3-, 6-, and 12-fold increased HOB concentration via HOB infusion. Systemic, cerebral, and skeletal muscle HOB kinetics, oxidation, glucose turnover, and lipolysis via arterial, jugular, and femoral venous differences in combination with stable isotopically labeled HOB, glucose, and glycerol, infusion. An increase in HOB from the basal 160-450 μmol/L elicited 14 ± 2% reduction (P = .03) in glucose appearance and 37 ± 4% decrease (P = .03) in lipolytic rate while insulin and glucagon were unchanged. Endogenous HOB appearance was reduced in a dose-dependent manner with complete inhibition at the highest HOB concentration (1.7 mmol/L). Cerebral HOB uptake and subsequent oxidation was linearly related to the arterial HOB concentration. Resting skeletal muscle HOB uptake showed saturation kinetics. A small increase in the HOB concentration decreases glucose production and lipolysis in post-absorptive healthy males. Moreover, cerebral HOB uptake and oxidation rates are linearly related to the arterial HOB concentration of importance for modifying brain energy utilization, potentially of relevance for patients with epileptic seizures and dementia.

  4. [Metabolic response to stress, can we control it?].

    Science.gov (United States)

    Longarela, A; Olarra, J; Suárez, L; García de Lorenzo, A

    2000-01-01

    When faced by an external aggression such as shock, sepsis, burns or surgery, the body develops a response, known as stress, comprising hypermetabolism and hypercatabolism related to an alteration in tissue sensitivity to insulin. This alteration seems to be rooted in the transmembrane protein GLUT-4 which takes care of the cell uptake of glucose in skeletal muscle. As a result, there are alterations in the metabolism of carbohydrates, fats and proteins (reduction of immunoglobulins). In the case of surgery, it has been shown that, on the one hand, factors such as rest, pre-operative fasting or the release of inflammatory response factors constrain an even greater alteration in the sensitivity to insulin; and on the other hand that the degree of resistance to insulin depends on the magnitude of the surgery, its duration, bleeding, or on hypothermia and extracorporeal circulation in the case of heart surgery. These metabolic alterations may lead to an increase in the number of infections, mean stay in hospital, and even lead to diabetes mellitus in the long term. Over the last few years, all of this has led several researchers to try to minimize the stress response associated with planned surgery through replacing pre-operative fasting by the administration of carbohydrates, whether or not in association with insulin in perfusion. Beneficial results have been described: control of hyperglycaemia, lower consumption of neoglycogenic amino acids and less alteration of plasma immunity (interleukins, TNF). Future studies will evaluate the influence of these measures on plasma immunity, mean hospital stay and morbidity/mortality.

  5. Cerebral blood volume and blood flow responses to hyperventilation in brain tumors during isoflurane or propofol anesthesia.

    Science.gov (United States)

    Cenic, Aleksa; Craen, Rosemary A; Lee, Ting-Yim; Gelb, Adrian W

    2002-03-01

    Using computerized tomography, we measured absolute cerebral blood flow (CBF) and cerebral blood volume (CBV) in tumor, peri-tumor, and contralateral normal regions, at normocapnia and hypocapnia, in 16 rabbits with brain tumors (VX2 carcinoma), under isoflurane or propofol anesthesia. In both anesthetic groups, CBV and CBF were highest in the tumor region and lowest in the contralateral normal tissue. For isoflurane, a significant decrease in both CBV and CBF was observed in all tissue regions with hyperventilation (P hyperventilation for all regions (P > 0.10). In addition, there were no differences between CBV values for isoflurane at hypocapnia when compared with CBV values for propofol at normo- or hypocapnia (P > 0.34 and P > 0.35, respectively, in the tumor regions). Our results indicate that propofol increases cerebral vascular tone in both neoplastic and normal tissue vessels compared with isoflurane. CBV and CBF during normocapnia were significantly greater in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol. CBV and CBF remained responsive to hyperventilation only with isoflurane. In rabbits with brain tumors, brain blood flow and volume were significantly larger in all regions (tumor, peri-tumor, and contralateral normal tissue) with isoflurane than with propofol during normocapnia, and remained responsive to a reduction in PaCO(2). Consequently, during hypocapnia, brain blood flow and volume values with isoflurane were similar to values with propofol.

  6. Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy.

    Directory of Open Access Journals (Sweden)

    Brenda eBartnik-Olson

    2013-10-01

    Full Text Available The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI and the use of 13C labeled substrates and nuclear magnetic resonance (NMR spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle.

  7. Metabolic and psychological response to 7-day fasting in obese patients with and without metabolic syndrome.

    Science.gov (United States)

    Li, Chenying; Ostermann, Thomas; Hardt, Monika; Lüdtke, Rainer; Broecker-Preuss, Martina; Dobos, Gustav; Michalsen, Andreas

    2013-01-01

    Extended modified fasting is a frequently practiced tradition in Europe. It is claimed to improve the cardiometabolic state and physical and psychological well-being by an evolutionary co-developed adaptation response. We aimed to investigate the cardiometabolic and psychological effects of a 7-day fast and differences of these responses between patients with or without metabolic syndrome (MetS). We investigated 30 female subjects (49.0 ± 8.1 years, BMI 30.4 ± 6.7 kg/m(2)) with (n = 12) and without (n = 18) MetS. All subjects participated in a 7-day fast according to Buchinger with a nutritional energy intake of 300 kcal/day and stepwise reintroduction of solid food thereafter. Outcomes were assessed baseline and after fasting and included measures of metabolic and glucoregulatory control, adipokines as well as psychological well-being as assessed by Profile of Mood States (POMS) and Hospital Anxiety and Depression Scale (HADS). Mean weight decreased from 85.4 ± 18.8 kg to 79.7 ± 18.2 kg accompanied by systolic/diastolic blood pressure (BP) reduction of -16.2 mm Hg (95% CI: -9.1; -23.3 mm Hg) and -6.0 mm Hg (95% CI: -1.8; -10.3 mm Hg), each p Fasting led to marked decreases of levels of LDL-cholesterol, leptin, and insulin and increases of levels of adiponectin, leptin receptors, and resistin. Fasting-induced mood enhancement was reflected by decreased anxiety, depression, fatigue, and improved vigor. Patients with MetS showed some greater changes in B P, LDL-cholesterol, triglycerides, adiponectin, leptin, and sleep quality. Fasting was well-tolerated. Our results point to marked beneficial responses to 7-day modified fasting and a potential role in the prevention of the MetS. Randomized trials with longer observation periods should test the clinical effectiveness of fasting in metabolic diseases. © 2014 S. Karger GmbH, Freiburg.

  8. Differential producibility analysis (DPA of transcriptomic data with metabolic networks: deconstructing the metabolic response of M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bhushan K Bonde

    2011-06-01

    Full Text Available A general paucity of knowledge about the metabolic state of Mycobacterium tuberculosis within the host environment is a major factor impeding development of novel drugs against tuberculosis. Current experimental methods do not allow direct determination of the global metabolic state of a bacterial pathogen in vivo, but the transcriptional activity of all encoded genes has been investigated in numerous microarray studies. We describe a novel algorithm, Differential Producibility Analysis (DPA that uses a metabolic network to extract metabolic signals from transcriptome data. The method utilizes Flux Balance Analysis (FBA to identify the set of genes that affect the ability to produce each metabolite in the network. Subsequently, Rank Product Analysis is used to identify those metabolites predicted to be most affected by a transcriptional signal. We first apply DPA to investigate the metabolic response of E. coli to both anaerobic growth and inactivation of the FNR global regulator. DPA successfully extracts metabolic signals that correspond to experimental data and provides novel metabolic insights. We next apply DPA to investigate the metabolic response of M. tuberculosis to the macrophage environment, human sputum and a range of in vitro environmental perturbations. The analysis revealed a previously unrecognized feature of the response of M. tuberculosis to the macrophage environment: a down-regulation of genes influencing metabolites in central metabolism and concomitant up-regulation of genes that influence synthesis of cell wall components and virulence factors. DPA suggests that a significant feature of the response of the tubercle bacillus to the intracellular environment is a channeling of resources towards remodeling of its cell envelope, possibly in preparation for attack by host defenses. DPA may be used to unravel the mechanisms of virulence and persistence of M. tuberculosis and other pathogens and may have general application for

  9. Do diabetes and obesity affect the metabolic response to exercise?

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Weigert, Cora

    2017-01-01

    PURPOSE OF REVIEW: Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. RECENT FINDINGS: Poor glycemic...... of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent...... on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. SUMMARY: Severe metabolic dysregulation can reduce the benefit from...

  10. Cell Wall Metabolism in Response to Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Hyacinthe Le Gall

    2015-02-01

    Full Text Available This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic, transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i an increased level in xyloglucan endotransglucosylase/hydrolase (XTH and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions.

  11. Proprioceptive evoked potentials in man: cerebral responses to changing weight loads on the hand

    DEFF Research Database (Denmark)

    Arnfred, S; He, Chen; Eder, D

    2000-01-01

    We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a change in weight of 400-480 g in ten subjects. Rise-time was 20g/10 ms, Inter Stimulus Interval 2s and stimulus duration was 100 ms. The cerebral activations were a double positive contralateral C3'/P70......). Further studies of the PEP are needed to assess the influence of load manipulations and of muscle contraction and to explore the effect of attentional manipulation....

  12. Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

    DEFF Research Database (Denmark)

    Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

    2003-01-01

    Delayed structural cerebral sequelae has been reported following cranial radiation therapy (CRT) to children with primary brain tumors, but little is known about potential functional changes. Twenty-four patients were included, diagnosed and treated at a median age of 11 years, and examined after...

  13. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    DEFF Research Database (Denmark)

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

  14. Electromyographic, cerebral and muscle hemodynamic responses during intermittent, isometric contractions of the biceps brachii at three submaximal intensities

    Directory of Open Access Journals (Sweden)

    Yagesh eBhambhani

    2014-06-01

    Full Text Available This study examined the electromyographic, cerebral and muscle hemodynamic responses during intermittent isometric contractions of biceps brachii at 20%, 40% and 60% of maximal voluntary contraction (MVC. Eleven volunteers completed two minutes of intermittent isometric contractions (12/min at an elbow angle of 90° interspersed with three minutes rest between intensities in systematic order. Surface electromyography (EMG was recorded from the right biceps brachii and near infrared spectroscopy (NIRS was used to simultaneously measure left prefrontal and right biceps brachii oxyhemoglobin (HbO2, deoxyhemoglobin (HHb and total hemoglobin (Hbtot. Transcranial Doppler ultrasound was used to measure middle cerebral artery velocity (MCAv bilaterally. Finger photoplethysmography was used to record beat-to-beat blood pressure and heart rate. EMG increased with force output from 20% to 60% MVC (P0.05. MCAv increased from rest to exercise but was not different among intensities (P>0.05. Force output correlated with the root mean square EMG and changes in muscle HbO2 (P0.05 at all three intensities. Force output declined by 8% from the 1st to the 24th contraction only at 60% MVC and was accompanied by systematic increases in RMS, cerebral HbO2 and Hbtot with a levelling off in muscle HbO2 and Hbtot. These changes were independent of alterations in mean arterial pressure. Since cerebral blood flow and oxygenation were elevated at 60% MVC, we attribute the development of fatigue to reduced muscle oxygen availability rather than impaired central n

  15. Electromyographic, cerebral, and muscle hemodynamic responses during intermittent, isometric contractions of the biceps brachii at three submaximal intensities

    Science.gov (United States)

    Bhambhani, Yagesh; Fan, Jui-Lin; Place, Nicolas; Rodriguez-Falces, Javier; Kayser, Bengt

    2014-01-01

    This study examined the electromyographic, cerebral and muscle hemodynamic responses during intermittent isometric contractions of biceps brachii at 20, 40, and 60% of maximal voluntary contraction (MVC). Eleven volunteers completed 2 min of intermittent isometric contractions (12/min) at an elbow angle of 90° interspersed with 3 min rest between intensities in systematic order. Surface electromyography (EMG) was recorded from the right biceps brachii and near infrared spectroscopy (NIRS) was used to simultaneously measure left prefrontal and right biceps brachii oxyhemoglobin (HbO2), deoxyhemoglobin (HHb), and total hemoglobin (Hbtot). Transcranial Doppler ultrasound was used to measure middle cerebral artery velocity (MCAv) bilaterally. Finger photoplethysmography was used to record beat-to-beat blood pressure and heart rate. EMG increased with force output from 20 to 60% MVC (P MVC (P MVC (P MVC (P > 0.05). MCAv increased from rest to exercise but was not different among intensities (P > 0.05). Force output correlated with the root mean square EMG and changes in muscle HbO2 (P 0.05) at all three intensities. Force output declined by 8% from the 1st to the 24th contraction only at 60% MVC and was accompanied by systematic increases in RMS, cerebral HbO2 and Hbtot with a leveling off in muscle HbO2 and Hbtot. These changes were independent of alterations in mean arterial pressure. Since cerebral blood flow and oxygenation were elevated at 60% MVC, we attribute the development of fatigue to reduced muscle oxygen availability rather than impaired central neuronal activation. PMID:24966837

  16. Specific and Complex Reprogramming of Cellular Metabolism in Myeloid Cells during Innate Immune Responses

    NARCIS (Netherlands)

    Stienstra, R.; Netea-Maier, R.T.; Riksen, N.P.; Joosten, L.A.B.; Netea, M.G.

    2017-01-01

    Renewed interest in immune cell metabolism has led to the emergence of a research field aimed at studying the importance of metabolic processes for an effective immune response. In addition to the adaptive immune system, cells of the myeloid lineage have been shown to undergo robust metabolic

  17. Specific and Complex Reprogramming of Cellular Metabolism in Myeloid Cells during Innate Immune Responses

    NARCIS (Netherlands)

    Stienstra, Rinke; Netea-Maier, Romana T.; Riksen, Niels P.; Joosten, Leo A.B.; Netea, Mihai G.

    2017-01-01

    Renewed interest in immune cell metabolism has led to the emergence of a research field aimed at studying the importance of metabolic processes for an effective immune response. In addition to the adaptive immune system, cells of the myeloid lineage have been shown to undergo robust metabolic

  18. Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt

    Science.gov (United States)

    Frey, Mary A. B.; Mader, Thomas H.; Bagian, James P.; Charles, John B.; Meehan, Richard T.

    1993-01-01

    Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of space flight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 deg head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

  19. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  20. The effects of anticholinergic drugs on regional cerebral blood flow, and oxygen metabolism in previously untreated patients with Parkinson`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Satoko; Takahashi, Satoshi; Yonezawa, Hisashi; Sato, Yoshitomo [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1998-12-01

    Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO{sub 2}) were measured using the steady-state {sup 15}O technique and positron emission tomography (PET) in six previously untreated patients with Parkinson`s disease before and after trihexyphenidyl (THP) treatment. The patients comprised of 4 men and 2 women with Hoehn-Yahr stage II-III. Their ages at the onset of the study ranged from 46 to 57 years (mean{+-}SD, 51.8{+-}3.7) and the duration of the illness ranged from 10 to 48 months (mean{+-}SD, 28.8{+-}15.5). The PET study, assessments of the disability and cognitive function were undergone twice. The first time assessments were done was when the patients were not receiving any drugs, and the second time was one to three months after administration of 6 mg THP. All patients showed clinical improvement after THP treatment. The mean disability score of Unified Parkinson`s Disease Rating Scale decreased from 35.1 (SD{+-}11.3) to 25.7 (SD{+-}11.6). The cognitive function assessed by Hasegawa`s dementia rating scale-revised, Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, and Wechsler Memory Scale-Revised, were not significantly different before and after the THP treatment. After the THP treatment, rCBF and rCMRO{sub 2} decreased significantly in the striatum (about 15%) and all cerebral cortices (about 10%) on both sides contralateral and ipsilateral to the predominantly symptomatic limbs. We conclude that an anticholinergic THP decreases the rCBF and rCMRO{sub 2} significantly in the cerebral cortices without cognitive impairment in early untreated patients with Parkinson`s disease. (author)

  1. Effects of constraint-induced movement therapy on brain glucose metabolism in a rat model of cerebral ischemia: a micro PET/CT study.

    Science.gov (United States)

    Li, Ying-Ying; Zhang, Bei; Yu, Ke-Wei; Li, Ce; Xie, Hong-Yu; Bao, Wei-Qi; Kong, Yan-Yan; Jiao, Fang-Yang; Guan, Yi-Hui; Bai, Yu-Long

    2018-01-04

    Constraint-induced movement therapy (CIMT) can improve motor functions in stroke patients and ischemic rats. This study examined the effect of CIMT in ischemic rats using positron emission tomography (PET). We used middle cerebral artery occlusion (MCAO) procedure to induce cerebral ischemia in rats. Male rats were divided into a negative control group (Normal, n = 4), a sham-operated group (Sham, n = 6), an ischemic group (Control, n = 6) and an ischemic CIMT-treated group (CIMT, n = 6). CIMT started at postoperative day 8 (d8) and lasted for 2 weeks. We utilized 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) micro PET/CT imaging to evaluate glucose metabolism in different brain regions at baseline, before, and after treatment, respectively. CIMT improved behavioral performance in the ischemic CIMT group. At the end of treatment, the CIMT group showed lower standardized uptake values (SUVs) in the ipsilateral cingulate, motor and somatosensory cortex, respectively; as well as the anterodorsal hippocampus compared to the Control group (1.80% ± 0.10% vs. 1.92% ± 0.08%, 1.32% ± 0.14% vs. 1.48% ± 0.09%, 1.18% ± 0.14% vs. 1.42% ± 0.15%, 1.68% ± 0.09% vs. 1.79% ± 0.06%, P cerebral ischemic rats and this effect can be attributed to increased glucose utilization in the contralateral hemisphere.

  2. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans

    Science.gov (United States)

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2014-01-01

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial–venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12–23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P dehydration accelerated the decline in CBF by decreasing and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. PMID:24835170

  3. The effect of a metabolic inhibitor upon the properties of the cerebral vasculature during a whole-head saline perfusion of the rat.

    Science.gov (United States)

    Luthert, P J; Greenwood, J; Pratt, O E; Lantos, P L

    1987-01-01

    The effect of the metabolic inhibitor 2,4-dinitrophenol (DNP) has been assessed during a simple in situ Ringer solution perfusion of the rat brain. The preparation was perfused, with or without the addition of DNP, for periods ranging up to 30 min. Following this pre-test perfusion, both the vascular permeability and cerebral perfusate flow were assessed. In the absence of DNP significant barrier disruption had taken place by 10 min and the flow rates showed greater fluctuations with time. In the presence of DNP, however, perfusate flow remained constant and the blood-brain barrier remained intact to [14C]mannitol for at least 10 min, but subsequently the flow rate dropped and the barrier began to show evidence of disruption. The unbound visual marker, Evans Blue, was apparently excluded from all regions other than those that are known to lack a blood-brain barrier. The water content of the brain showed no significant increase until 20 min. Patency of the capillaries was demonstrated by direct visualization of the cerebral vasculature with an Indian ink-gelatin mixture and in some animals there was evidence of incomplete filling following 30 min of perfusion. It is concluded that the use of DNP in the perfusate provides a useful preparation for the short-term study of passive properties of the blood-brain barrier, such as carrier-facilitated diffusion, as well as mechanisms of barrier opening.

  4. [Nicergoline, an ergot alkaloid, improves ischemic brain damage by ameliorating the decreased cerebral blood flow and metabolism in spontaneously hypertensive rats].

    Science.gov (United States)

    Ueda, T; Ishikawa, T; Kawata, K; Setoyama, K; Maekawa, T; Sakabe, T; Takeshita, H

    1992-12-01

    Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF: 14C-iodoantipyrine) and glucose utilization (LCGU: 14C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed; the permanent BCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8 mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100 micrograms/kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP), parietal cortex (PC), thalamus (TH), hypothalamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease in LCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is concluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism following brain ischemia.

  5. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    OpenAIRE

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2015-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D recep...

  6. The Bidirectional Relationship between Metabolism and Immune Responses

    OpenAIRE

    Raval, Forum M.; Nikolajczyk, Barbara S.

    2013-01-01

    Immunometabolism investigates the multiple links between the immune system and metabolism. One main focus of immunometabolism investigates how obesity impacts the immune system and pro-inflammatory immune cell function, leading to metabolic diseases, including type 2 diabetes (T2D). The second focus stresses the metabolic changes that dictate immune cell activation. Several groups have studied these two arms of the field individually, but work that integrates both topics will be required to d...

  7. Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

    DEFF Research Database (Denmark)

    Hougaard, Anders; Jensen, Bettina Hagström; Amin, Faisal Mohammad

    2015-01-01

    was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual......MRI) in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness......, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial...

  8. Muscle response to heavy resistance exercise in children with spastic cerebral palsy.

    Science.gov (United States)

    Damiano, D L; Vaughan, C L; Abel, M F

    1995-08-01

    Fourteen ambulatory children with spastic diplegia participated in a bilateral quadriceps strengthening program in an attempt to decrease the amount of knee crouch during gait. Each child exercised three times a week for six weeks using free ankle weights at a load of 65 per cent of maximum. A normal comparison group of 25 children was also tested under identical conditions. Children with cerebral palsy were significantly weaker in the quadriceps and hamstrings muscle groups than controls. Quadriceps strength increased significantly at all three angles of knee flexion as a result of the weight-training program and did not differ statistically from normal at the end of the program. Quadriceps weakness was shown to be a factor in crouch gait; restoring strength through resistance exercise may be a useful adjunct in the treatment of cerebral palsy.

  9. Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study

    DEFF Research Database (Denmark)

    Bartek, Jiri; Thelin, Eric Peter; Ghatan, Per Hamid

    2016-01-01

    in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM. METHODS: From a prior study on patients (n = 52......INTRODUCTION: Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism......) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP...

  10. [Hemiplegia in posterior cerebral artery infarctions: analysis of various responsible mechanisms].

    Science.gov (United States)

    Ortiz, N; Barraquer Bordas, L; Dourado, M; Rey, A; Avila, A

    1993-01-01

    When cerebral infarction determines hemiplegia or hemiparesia which accompany a hemilateral sensitive deficit and hemianopsia and even neuropsychologic symptoms (aphasic alterations in the case of injury to the left hemisphere, heminegligence and anosognosy in the case of injury to the right hemisphere) the involvement of a sylvian artery syndrome is usually considered. Nonetheless, recent contributions have reported that such symptoms may appear in infarctions of the territory of the posterior cerebral artery. Two clinical-radiologic observations in this line are presented. Nuclear magnetic resonance demonstrated injury to the posterior arm of the internal capsule in one case and in the other the lesion developed over three times, in the latter of which injury to the cerebral peduncle was produced causing hemiparesia. The authors emphasize that hemiplegia or hemiparesia in some infarctions of the posterior cerebral artery may be due to 1) mesencephalic infarction in the posterior plane of the retromamillar Foix and Hillemand pediculum (or G. Lazorthes interpedunculum), 2) infarction or "ischemic penumbra" in the internal capsule by involvement of any of the perforating branches of the posterior cerebrum irrigating the thalamus, except for the medial posterior choroid artery or even of the Foix and Hillemand thalamus-tuberian pediculum (or Lazorthes inferior and anterior) which principally initiates at the posterior communicating branch with a fragment of the posterior branch of the internal capsule perhaps not always being under its control. In this case, the thrombus occupying the posterior cerebrum may extend to the cited communicating branch or a hemodynamic deficit may be produced in the territory of the same.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

    OpenAIRE

    PhD, Farzaneh

    2008-01-01

    Farzaneh A Sorond1,2, Lewis A Lipsitz2,4, Norman K Hollenberg3,5, Naomi DL Fisher31Department of Neurology, Stroke Division; 2Institute for Aging Research, Hebrew SeniorLife, Boston, MA; 3Department of Medicine, Endocrine-Hypertension Division; 4Department of Medicine, Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Department of Radiology, Brigham and Women’s Hospital, Boston, MABackground and Purpose: Cerebral ischemia is a common, morbid condition accompanied...

  12. Proteomic analysis and comparison of intra- and extracranial cerebral atherosclerosis responses to hyperlipidemia in rabbits

    OpenAIRE

    Tu, Zhi-Lan; Yu, Bo; Huang, Dong-Ya; Ojha, Rajeev; Zhou, Shu-Kui; An, He-Di; Liu, Rong; Du, Cui; Shen, Nan; Fu, Jian-Hui; Hou, Shuang-Xing

    2017-01-01

    The present study aimed to investigate protein expression levels of intra- and extracranial atherosclerosis in rabbits following administration of a high-fat diet. Rabbits were randomly divided into control (group A; n=9) and high-fat diet (group B; n=9) groups. At week 12, tissues were sectioned from the common carotid artery (CCA) and middle cerebral artery (MCA). Pathological analysis was performed. Differential protein expression levels were examined by 2-D gel electrophoresis (2-DE) and ...

  13. Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

    Science.gov (United States)

    Alamgir, Kabir Md; Hojo, Yuko; Christeller, John T; Fukumoto, Kaori; Isshiki, Ryutaro; Shinya, Tomonori; Baldwin, Ian T; Galis, Ivan

    2016-02-01

    Plants defend against attack from herbivores by direct and indirect defence mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defence metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biassed metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defence metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. © 2015 John Wiley & Sons Ltd.

  14. Exercise heat stress and metabolism.

    Science.gov (United States)

    Mündel, Toby

    2008-01-01

    Apart from few studies, the majority of the research conducted on the effects of heat stress on energy metabolism during exercise has only been done so in the past two decades. Whilst increasing exercise duration under conditions of heat stress favours the oxidation of carbohydrate (CHO) and appears to increase the rate of muscle glycogenolysis, total CHO oxidation is often less and levels of muscle glycogen remain much higher at the point of fatigue when compared with the same exercise without heat stress. Furthermore, supplementing CHO during exercise in the heat appears to exert an ergogenic effect that is not related to 'peripheral' but rather 'central' factors. However, there may be a role for the excess ammonia (NH3) produced in the exercising muscle during heat stress, as cerebral uptake and subsequent metabolism of NH3 may have detrimental effects on cerebral function. Recent exciting results point toward an increased cerebral CHO uptake relative to that of O2, termed the cerebral metabolic ratio (CMR) during exercise with heat stress, although a causative link between this and reduced exercise performance has yet to be identified. Therefore, it appears that despite a shift towards greater CHO utilisation in both skeletal muscular and cerebral metabolism, these responses have ultimately not proved limiting to exercise with heat stress.

  15. Dose-response relationship of locally applied nimodipine in an ex vivo model of cerebral vasospasm.

    Science.gov (United States)

    Seker, Fatih; Hesser, Jürgen; Neumaier-Probst, Eva; Groden, Christoph; Brockmann, Marc A; Schubert, Rudolf; Brockmann, Carolin

    2013-01-01

    Cerebral vasospasm is a severe complication of subarachnoid hemorrhage (SAH). The calcium channel inhibitor nimodipine has been used for treatment of cerebral vasospasm. No evidence-based recommendations for local nimodipine administration at the site of vasospasm exist. The purpose of this study was to quantify nimodipine's local vasodilatory effect in an ex vivo model of SAH-induced vasospasm. SAH-induced vasospasm was modeled by contracting isolated segments of rat superior cerebellar arteries with a combination of serotonin and a synthetic analog of prostaglandin A(2). A pressure myograph system was used to determine vessel reactivity of spastic as well as non-spastic arteries. Compared to the initial vessel diameter, a combination of serotonin and prostaglandin induced considerable vasospasm (55 ± 2.5 % contraction; n = 12; p nimodipine dilated the arteries in a concentration-dependent manner starting at concentrations as low as 1 nM (n = 12; p Nimodipine's vasodilatory effect was smaller in spastic than in non-spastic vessels (n = 12; p nimodipine have a strong vasodilatory effect, which is of relevance when considering the local application of nimodipine in cerebral vasospasm.

  16. Metabolic and Cardiovascular Response to Shallow Water Exercise in Young and Older Women.

    Science.gov (United States)

    Campbell, Jennifer A.; D'Acquisto, Leo J.; D'Acquisto, Debra M.; Cline, Michael G.

    2003-01-01

    Compared the metabolic and cardiovascular responses of young and older women while performing shallow water exercise (SWE). Overall, SWE elicited metabolic and cardiovascular responses that met American College of Sports Medicine's guidelines for establishing health benefits. Older females self-selected a greater relative exercise intensity during…

  17. Supplementation of Saccharomyces cerevisiae modulates the metabolic response to lipopolysaccharide challenge in feedlot steers

    Science.gov (United States)

    Live yeast has the potential to serve as an alternative to the use of low-dose supplementation of antibiotics in cattle due to the ability to alter ruminant metabolism; which in turn may influence the immune response. Therefore, the objective of this study was to determine the metabolic response to ...

  18. Acute metabolic response to fasted and postprandial exercise

    Directory of Open Access Journals (Sweden)

    Lima FD

    2015-08-01

    Full Text Available Filipe Dinato de Lima,1,2 Ana Luiza Matias Correia,1 Denilson da Silva Teixeira,2 Domingos Vasco da Silva Neto,2 Ítalo Sávio Gonçalves Fernandes,2 Mário Boratto Xavier Viana,2 Mateus Petitto,2 Rodney Antônio da Silva Sampaio,2 Sandro Nobre Chaves,2 Simone Teixeira Alves,2 Renata Aparecida Elias Dantas,2 Márcio Rabelo Mota2 1University of Brasília, Brasília, DF, Brazil; 2Universitary Center of Brasília (UniCEUB, Brasília, DF, BrazilAbstract: The aim of this study was to analyze the acute metabolic response to exercise in fasting and postprandial. For this, ten individuals were submitted to an incremental treadmill test, with an initial speed of 5 and 1 km/h increments every minute, with no inclination, and a body composition assessment. After this 1st day, all volunteers were submitted to two experimental procedures (fasting and postprandial, with an aerobic exercise performed for 36 minutes at 65% of maximal oxygen consumption. At postprandial procedure, all subjects ingested a breakfast containing 59.3 g of carbohydrate (76.73%, 9.97 g of protein (12.90%, 8.01 g of lipids (10.37%, with a total energy intake of 349.17 kcal. An analysis of plasma concentration of triglycerides, lactate, and glucose was performed in two stages: before and after exercise. The Shapiro–Wilk test was used to verify the normality of the data. For analysis of glucose concentration, plasma lactate, and triglycerides, we used a repeated measures analysis of variance factorial 2×2, with Bonferroni multiple comparison test. The significance level of P<0.05 was adopted. The results indicated a maintenance level of glucose at fasting and a decrease in glucose concentration at postprandial exercise. Both conditions increase plasma lactate. Triglycerides also increased in the two experimental conditions; however, after exercise fasting, the increase was significantly higher than in the postprandial exercise. These data suggest that both exercises could increase

  19. Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

    Directory of Open Access Journals (Sweden)

    Akιn Ata

    2007-12-01

    Full Text Available Abstract Background It is a daunting task to identify all the metabolic pathways of brain energy metabolism and develop a dynamic simulation environment that will cover a time scale ranging from seconds to hours. To simplify this task and make it more practicable, we undertook stoichiometric modeling of brain energy metabolism with the major aim of including the main interacting pathways in and between astrocytes and neurons. Model The constructed model includes central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, lipid metabolism, reactive oxygen species (ROS detoxification, amino acid metabolism (synthesis and catabolism, the well-known glutamate-glutamine cycle, other coupling reactions between astrocytes and neurons, and neurotransmitter metabolism. This is, to our knowledge, the most comprehensive attempt at stoichiometric modeling of brain metabolism to date in terms of its coverage of a wide range of metabolic pathways. We then attempted to model the basal physiological behaviour and hypoxic behaviour of the brain cells where astrocytes and neurons are tightly coupled. Results The reconstructed stoichiometric reaction model included 217 reactions (184 internal, 33 exchange and 216 metabolites (183 internal, 33 external distributed in and between astrocytes and neurons. Flux balance analysis (FBA techniques were applied to the reconstructed model to elucidate the underlying cellular principles of neuron-astrocyte coupling. Simulation of resting conditions under the constraints of maximization of glutamate/glutamine/GABA cycle fluxes between the two cell types with subsequent minimization of Euclidean norm of fluxes resulted in a flux distribution in accordance with literature-based findings. As a further validation of our model, the effect of oxygen deprivation (hypoxia on fluxes was simulated using an FBA-derivative approach, known as minimization of metabolic adjustment (MOMA. The results show the power of the

  20. The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

    Directory of Open Access Journals (Sweden)

    Kasper W. ter Horst

    2017-11-01

    Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (pathophysiologically involved in fructose metabolism and metabolic health.

  1. Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

    Science.gov (United States)

    Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

    2017-05-01

    Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

  2. Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2008-01-01

    Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

  3. Specific and Complex Reprogramming of Cellular Metabolism in Myeloid Cells during Innate Immune Responses.

    Science.gov (United States)

    Stienstra, Rinke; Netea-Maier, Romana T; Riksen, Niels P; Joosten, Leo A B; Netea, Mihai G

    2017-07-05

    Renewed interest in immune cell metabolism has led to the emergence of a research field aimed at studying the importance of metabolic processes for an effective immune response. In addition to the adaptive immune system, cells of the myeloid lineage have been shown to undergo robust metabolic changes upon activation. Whereas the specific metabolic requirements of myeloid cells after lipopolysaccharide/TLR4 stimulation have been extensively studied, recent evidence suggested that this model does not represent a metabolic blueprint for activated myeloid cells. Instead, different microbial stimuli, pathogens, or tissue microenvironments lead to specific and complex metabolic rewiring of myeloid cells. Here we present an overview of the metabolic heterogeneity in activated myeloid cells during health and disease. Directions for future research are suggested to ultimately provide new therapeutic opportunities. The uniqueness of metabolic signatures accompanying different conditions will require tailor-made interventions to ultimately modulate aberrant myeloid cell activation during disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cerebral blood flow and the response to acetazolamide during the acute, subacute, and chronic stages of aneurysmal subarachnoid hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Akira; Yoshinaga, Shinya; Nakayama, Yoshiya; Tomonaga, Masamichi [Fukuoka Univ., Chikushino (Japan). Chikushi Hospital

    1998-10-01

    Cerebral blood flow (CBF) and response to acetazolamide were measured during the acute, subacute, and chronic stages after aneurysmal subarachnoid hemorrhage and correlated with symptomatic vasospasm and clinical outcome in 45 patients who underwent early clipping of ruptured cerebral aneurysms, of whom 18 had symptomatic vasospasm and 27 did not. Xenon-enhanced CT was used to measure CBF in both groups during the acute, subacute, and chronic stages, defined as days 0-4, 5-20, and {>=}21, respectively. Vasoresponse was assessed by the CBF increase in response to 1 g of acetazolamide administered after the baseline CBF study, except in the subacute stage of patients with symptomatic vasospasm. Outcome was scored based on activities of daily living 2-3 months after subarachnoid hemorrhage. CBF values and the response to acetazolamide were preserved during the acute stage but CBF values fell considerably below control values during the subacute stage in patients with vasospasm. The regions with flow values below 15 ml/100 g/min subsequently converted to infarction and the regions with those above 19 ml/100 g/min remained intact without infarction. During the chronic stage, low CBF persisted, but the response to acetazolamide was higher than that of the control group. Outcome scores were good and fair. CBF values were normal during all stages in patients without vasospasm. The response to acetazolamide fell transiently during the subacute stage. All outcome scores were excellent. In conclusion, the CBF informations soon after the onset of symptomatic vasospasm are useful to predict a reversibility of ischemic brain tissue and a final outcome. (K.H.)

  5. Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism.

    NARCIS (Netherlands)

    Steinfeld, R.; Grapp, M.; Kraetzner, R.; Dreha-Kulaczewski, S.; Helms, G.; Dechent, P.; Wevers, R.A.; Grosso, S.; Gartner, J.

    2009-01-01

    Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency. We identified an inherited

  6. Neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice

    DEFF Research Database (Denmark)

    Wiese, Lothar; Kurtzhals, Jørgen A L; Penkowa, Milena

    2006-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy in humans due to the infection with Plasmodium falciparum. Neuro-cognitive impairment following CM occurs in about 10% of the treated survivors, while the precise pathophysiological mechanism remains unknown. Metallothionein I + II (MT......, infected with Plasmodium berghei ANKA, were studied on day 7, day 9, and when presenting signs of CM on days 10-12. We investigated brain histopathology by immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling...

  7. Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

    Directory of Open Access Journals (Sweden)

    Hong Zhong

    2018-01-01

    Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

  8. Modulation of cerebral haemodynamic response to olfactory stimuli by emotional valence detected by functional magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Cristofer André Caous

    Full Text Available ABSTRACT Olfactory perception, although restricted to just a few contexts in everyday life, is key in medicine. Several dementia conditions have been associated with early loss of olfactory discrimination. Despite the fact that several brain areas have been associated with olfaction in functional magnetic resonance imaging (fMRI, the mechanisms by which emotional valence is conveyed to the brain are not fully understood. Methods In this study, we compared cerebral activations by olfactory stimuli using different emotional valence stimuli on event-related fMRI. We used three standard olfactory odorants with different valence (positive, neutral and negative. Forty-three healthy subjects (22 males were scanned on a 3.0T MR system. Olfactory stimulation was attained through a delivery system synchronized with image acquisition and subjects´ breathing instructions. fMRI data analysis was performed by the FSL package (Oxford University including head movement correction, GLM modeling of the neurovascular (BOLD response and group activation maps produced at p<0.05 and corrected for multiple comparison. Results Increased cerebral responses within the anterior cingulate, amygdaloid nuclei, as well as the dorsolateral prefrontal, occipital and orbitofrontal cortices were observed in positive and negative valence conditions, while response to neutral valence arousal was less intense and not observed in the amygdaloid complex. The most significant statistical response aroused from the stimuli clusters was observed in the negative condition. Conclusion The results of the present study support the hypothesis that neutral stimuli may be more sensitive to early losses in pathological conditions, particularly dementia.

  9. Effects of reactive oxygen species on metabolism monitored by longitudinal {sup 1}H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    Energy Technology Data Exchange (ETDEWEB)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P [MRI Unit, Caen University Hospital, Caen, Normandy (France); Guillamo, J S; Lechapt-Zalcman, E; Valable, S [CERVOxy Group, CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen, Normandy (France); Lacombe, S; Houee Levin, C [Paris-Sud 11 University-CNRS, Orsay (France); Gauduel, Y A [LOA, Ecole Polytechnique - ENSTA ParisTech, Palaiseau (France); Dou, W [Tsinghua University, Beijing (China); Ruan, S [CReSTIC EA 3804, IUT Troyes, Troyes (France); Barre, L [GDMTEP, Group CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen (France); Rioult, F [CNRS UMR 6072, GREYC, Caen, Normandy (France); Derlon, J M [Neurosurgery and Neurology, Caen University Hospital, Caen, Normandy (France); Chapon, F [Pathology, Caen University Hospital, Caen, Normandy (France); Fong, V [Caen University (France); Kauffmann, F, E-mail: constans-jm@chu-caen.fr [Mathematics LMNO CNRS UMR 6139, Caen University, Caen, Normandy (France)

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  10. Effects of reactive oxygen species on metabolism monitored by longitudinal 1H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    Science.gov (United States)

    Constans, J. M.; Collet, S.; Guillamo, J. S.; Hossu, G.; Lacombe, S.; Gauduel, Y. A.; Houée Levin, C.; Dou, W.; Ruan, S.; Barré, L.; Rioult, F.; Derlon, J. M.; Lechapt-Zalcman, E.; Valable, S.; Chapon, F.; Courtheoux, P.; Fong, V.; Kauffmann, F.

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  11. Tidal switch on metabolic activity: Salinity induced responses on bacterioplankton metabolic capabilities in a tropical estuary

    Digital Repository Service at National Institute of Oceanography (India)

    Thottathil, S.D.; Balachandran, K.K.; Jayalakshmy, K.V.; Gupta, G.V.M.; Nair, S.

    -tolerant retrievable counts also accounted for the metabolic variation of bacterioplankton during low and high tides, respectively. The shift in the substrate utilization from carbohydrates to amino acids appears to be due to the physiological adaptation or nitrogen...

  12. Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure.

    Science.gov (United States)

    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hak Rim

    2017-03-01

    With the explosive increase in exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones, public concerns have grown over the last few decades with regard to the potential effects of EMF exposure on the nervous system in the brain. Many researchers have suggested that RF-EMFs can effect diverse neuronal alterations in the brain, thereby affecting neuronal functions as well as behavior. Previously, we showed that long-term exposure to 835 MHz RF-EMF induces autophagy in the mice brain. In this study, we explore whether short-term exposure to RF-EMF leads to the autophagy pathway in the cerebral cortex and brainstem at 835 MHz with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Increased levels of autophagy genes and proteins such as LC3B-II and Beclin1 were demonstrated and the accumulation of autophagosomes and autolysosomes was observed in cortical neurons whereas apoptosis pathways were up-regulated in the brainstem but not in the cortex following 4 weeks of RF exposure. Taken together, the present study indicates that monthly exposure to RF-EMF induces autophagy in the cerebral cortex and suggests that autophagic degradation in cortical neurons against a stress of 835 MHz RF during 4 weeks could correspond to adaptation to the RF stress environment. However, activation of apoptosis rather than autophagy in the brainstem is suggesting the differential responses to the RF-EMF stresses in the brain system.

  13. Differential regional cerebral glucose metabolism in clinical syndromes of frontotemporal lobar degeneration: a study with FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. M.; Cho, S. S.; Na, D. L.; Lee, K. H.; Choi, Y.; Choe, Y. S.; Kim, B. T.; Kim, S. E. [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    2001-07-01

    Frontotemporal lobar degeneration( FTLD) is the third most common dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neurobehavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patient with FTLD presented with four different clinical syndromes. We analysed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral premotor are was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical features of FTLD syndromes. These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD.

  14. Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome.

    Science.gov (United States)

    Elzinga, S E; Rohleder, B; Schanbacher, B; McQuerry, K; Barker, V D; Adams, A A

    2017-07-01

    Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a

  15. Climate Coping: Investigating Metabolic Responses in Crocosphaera watsonii

    Science.gov (United States)

    Harris, K.

    2016-02-01

    Climate change causes chemical alterations in the open oceans, such as warming which leads to stratification, affecting nutrient ratios. Changes in nutrient ratios result in species shifts and a change in phytoplankton physiology, affecting all marine life. Unicellular diazotrophic microorganisms play a vital role in our open ocean ecosystems. These organisms do so by implementing metabolic processes that contribute to various availability of nutrients including; nitrogen and carbon. The open ocean diazotrophs are represented by multiple strains of Crocosphaera watsonii. The specific aim of this study was to determine whether the phenotype in small and large strain C. watsonii differs, in response to exposure to altered temperature gradients, measured as changes in cell density, photosynthetic efficiency, and EPS production. Triplicate cultures of C. watsonii WH8501 and C. watsonii WH0003 were inoculated into 60 ml of sterile Vineyard Sound SO media at a 1:10 ratio. Each culture was grown under; warm light levels (˜63 µ E m-2 s-1) on a 14:10 day/night cycle at temperatures of 27oC or 29oC. C. watsonii WH8501 cultures were harvested on Day 11, and C. watsonii WH0003 cultures were harvested on Day 9. To evaluate cell growth, fluorescence measurements were taken daily. Aliquots of experimental cultures were evaluated for cell density using flow-cytrometry, photosynthetic efficiency using FIRe fluorescence, and EPS production using a TEP determination assay. Proteins were extracted and analyzed by LC-MS-MS mass spectrometry. There was a correlation between temperature and EPS production for the two strains, C. watsonii WH8501 had a significantly higher growth rate when grown at 29oC, and a lower growth rate at 27oC compared to C. watsonii WH0003. Cultures grown at 27oC produced more EPS than those grown at 29oC. However, overall C. watsonii WH0003 produced more EPS than C. watsonii WH8501. We an increase in the yield of photosystem II (Fv/Fm) in C. watsonii WH0003 vs

  16. Cardiovascular, hormonal and metabolic responses to graded exercise in juvenile diabetics with and without autonomic neuropathy

    DEFF Research Database (Denmark)

    Hilsted, J; Galbo, H; Christensen, N J

    1980-01-01

    Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had to...... to be more heavily stressed during exercise to reach a certain heart rate or catecholamine level. The relation between other metabolic and hormonal response is discussed.......Thirteen juvenile diabetics were studied in order to determine if decreased beat-to-beat variation during deep respiration, indicating abnormal autonomic nerve function, imply that cardiovascular, hormonal and metabolic responses are impaired. Patients with decreased beat-to-beat variation had...

  17. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Nanjing University of Aeronautics and Astronautics, College of Aivil Aviation, Nanjing, Jiangsu (China); Wen, Jiqiu; Li, Xue; Zhang, Zhe [Medical School of Nanjing University, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu (China); Lu, Hanzhang [University of Texas Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Liu, Wei [Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong (China); Liu, Hui [Siemens MR NEA Collaboration, Siemens Ltd., Shanghai (China); Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China)

    2016-06-15

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO{sub 2} was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min{sup -1} 100 g{sup -1}, P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO{sub 2} (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O{sub 2} min{sup -1} 100 g{sup -1}, P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO{sub 2}. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO{sub 2}. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO{sub 2}. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  18. Mapping of cerebral metabolic rate of oxygen using dynamic susceptibility contrast and blood oxygen level dependent MR imaging in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Gersing, Alexandra S.; Schwaiger, Benedikt J. [Technical University Munich, Klinikum rechts der Isar, Department of Neuroradiology, Munich (Germany); University of California, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Ankenbrank, Monika; Toth, Vivien; Bauer, Jan S.; Zimmer, Claus [Technical University Munich, Klinikum rechts der Isar, Department of Neuroradiology, Munich (Germany); Janssen, Insa [Technical University Munich, Department of Neurosurgery, Munich (Germany); Kooijman, Hendrik [Philips Healthcare, Hamburg (Germany); Wunderlich, Silke [Technical University Munich, Department of Neurology, Munich (Germany); Preibisch, Christine [Technical University Munich, Klinikum rechts der Isar, Department of Neuroradiology, Munich (Germany); Technical University Munich, Department of Neurology, Munich (Germany)

    2015-12-15

    MR-derived cerebral metabolic rate of oxygen utilization (CMRO{sub 2}) has been suggested to be analogous to PET-derived CMRO{sub 2} and therefore may be used for detection of viable tissue at risk for infarction. The purpose of this study was to evaluate MR-derived CMRO{sub 2} mapping in acute ischemic stroke in relation to established diffusion- and perfusion-weighted imaging. In 23 patients (mean age 63 ± 18.7 years, 11 women) with imaging findings for acute ischemic stroke, relative oxygen extraction fraction was calculated from quantitative transverse relaxation times (T2, T2*) and relative cerebral blood volume using a quantitative blood oxygenation level dependent (BOLD) approach in order to detect a local increase of deoxyhemoglobin. Relative CMRO{sub 2} (rCMRO{sub 2}) maps were calculated by multiplying relative oxygen extraction fraction (rOEF) by cerebral blood flow, derived from PWI. After co-registration, rCMRO{sub 2} maps were evaluated in comparison with apparent diffusion coefficient (ADC) and time-to-peak (TTP) maps. Mean rCMRO{sub 2} values in areas with diffusion-restriction or TTP/ADC mismatch were compared with rCMRO{sub 2} values in the contralateral tissue. In tissue with diffusion restriction, mean rCMRO{sub 2} values were significantly decreased compared to perfusion-impaired (17.9 [95 % confidence interval 10.3, 25.0] vs. 58.1 [95 % confidence interval 50.1, 70.3]; P < 0.001) and tissue in the contralateral hemisphere (68.2 [95 % confidence interval 61.4, 75.0]; P < 0.001). rCMRO{sub 2} in perfusion-impaired tissue showed no significant change compared to tissue in the contralateral hemisphere (58.1 [95 % confidence interval 50.1, 70.3] vs. 66.7 [95 % confidence interval 53.4, 73.4]; P = 0.34). MR-derived CMRO{sub 2} was decreased within diffusion-restricted tissue and stable within perfusion-impaired tissue, suggesting that this technique may be adequate to reveal different pathophysiological stages in acute stroke. (orig.)

  19. Ataque cerebral

    OpenAIRE

    Takeuchi Tan, Yuri; Fundación Valle de Lili

    1998-01-01

    ¿Qué es un ataque cerebral?/¿Qué tipos de ataque cerebral existen?/¿Cuáles son los síntomas de un ataque cerebral?/Factores de riesgo para un ataque cerebral/Tratamiento médico del ataque cerebral/¿por qué es importante acudir temprano cuando se presentan las señales de alarma?/ Manejo preventivo del ataque cerebral isquémico/Tratamiento quirúrgico del ataque cerebral/Enfermedad vascular cerebral hemorrágica/¿Cómo está constituido el grupo de ataque cerebral de la fundación Clínica Valle d...

  20. Whole-body CO2 production as an index of the metabolic response to sepsis

    Science.gov (United States)

    Whole-body carbon dioxide (CO2) production (RaCO2) is an index of substrate oxidation and energy expenditure; therefore, it may provide information about the metabolic response to sepsis. Using stable isotope techniques, we determined RaCO2 and its relationship to protein and glucose metabolism in m...

  1. Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition

    NARCIS (Netherlands)

    Sinha, Neeraj; Suarez-Diez, Maria; Schothorst, Van Evert M.; Keijer, Jaap; Martins dos Santos, Vitor; Hooiveld, Guido J.E.J.

    2017-01-01

    The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial

  2. Metabolic product response profiles of Cherax quadricarinatus towards white spot syndrome virus infection.

    Science.gov (United States)

    Fan, Weiwei; Ye, Yangfang; Chen, Zhen; Shao, Yina; Xie, Xiaolu; Zhang, Weiwei; Liu, Hai-Peng; Li, Chenghua

    2016-08-01

    White spot syndrome virus (WSSV) is one of the most devastating viral pathogens in both shrimp and crayfish farms, which often causes disease outbreak and leads to massive moralities with significant economic losses of aquaculture. However, limited research has been carried out on the intrinsic mechanisms toward WSSV challenge at the metabolic level. To gain comprehensive insight into metabolic responses induced by WSSV, we applied an NMR approach to investigate metabolic changes of crayfish gill and hepatopancreas infected by WSSV for 1, 6 and 12 h. In gill, an enhanced energy metabolism was observed in WSSV-challenged crayfish samples at 1 h, as marked by increased glucose, alanine, methionine, glutamate and uracil. Afterwards, energy metabolism, lipid metabolism as well as osmoregulation were markedly increased at 6 hpi, as shown by elevated glucose, alanine, methionine, fumarate, tyrosine, tryptophan, histidine, phosphorylcholine, betaine and uracil, whereas no obvious metabolites change was detected at 12 hpi. As for hepatopancreas, disturbed lipid metabolism and induced osmotic regulation was found at 6 hpi based on the metabolic biomarkers such as branched chain amino acids, threonine, alanine, methionine, glutamate, glutamine, tyrosine, phenylalanine, lactate and lipid. However, no obvious metabolic change was shown in hepatopancreas at both 1 hpi and 12 hpi. Taken together, our present results provided essential metabolic information about host-pathogen interactions in crayfish, which shed new light on our understanding of WSSV infection at metabolic level. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

    National Research Council Canada - National Science Library

    Yau, Shu H; McArthur, Genevieve; Badcock, Nicholas A; Brock, Jon

    2015-01-01

    .... Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech...

  4. Acute Neuroinflammation Promotes Cell Responses to 1800 MHz GSM Electromagnetic Fields in the Rat Cerebral Cortex.

    Science.gov (United States)

    Lameth, Julie; Gervais, Annie; Colin, Catherine; Lévêque, Philippe; Jay, Thérèse M; Edeline, Jean-Marc; Mallat, Michel

    2017-10-01

    Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

  5. METABOLIC AND HORMONAL RESPONSES TO ADRENOCEPTOR ANTAGONISTS IN EXERCISING RATS

    NARCIS (Netherlands)

    BENTHEM, L; VANDERLEEST, J; STEFFENS, AB; ZIJLSTRA, WG

    alpha- and beta-adrenoceptors play a key role in the regulation of nutrient supply to working muscles during exercise. To assess their influence in the regulation of substrate utilization, rats were studied during alpha- or beta-adrenoceptor blockade. Energy metabolism was studied by means of

  6. Basal metabolic regulatory responses and rhythmic activity of ...

    African Journals Online (AJOL)

    hope&shola

    2006-03-01

    Mar 1, 2006 ... activity of mammalian heart to aqueous kola nut extracts. Chukwu, L.O*, Odiete ... nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate .... contracture in frog striated muscle (Huxley and Taylor,. 1958). The xanthines stimulate ...

  7. Metabolic response to exogenous ethanol in yeast: An in vivo ...

    Indian Academy of Sciences (India)

    In this study, we applied this approach to evaluate the effects of increasing concentration of exogenous ethanol on the Saccharomyces cerevisiae fermentative metabolism. We show that the STOCSY analysis correctly identifies the different types of correlations among the enriched metabolites involved in the fermentation, ...

  8. Metabolic response to exogenous ethanol in yeast: An in vivo ...

    Indian Academy of Sciences (India)

    2012-08-02

    Aug 2, 2012 ... exogenous ethanol on the Saccharomyces cerevisiae fermentative metabolism. ... Exogenous stress; in vivo NMR; metabolomic; Saccharomyces cerevisiae; STOCSY .... Proton decoupled 13C-NMR spectra of yeast medium during fermentation: (a) representative spectra at the beginning and (b) at the end ...

  9. Bone metabolism and hand grip strength response to aerobic versus ...

    African Journals Online (AJOL)

    Currently, our understanding of how to use exercise effectively in diabetic patients in prevention of osteoporosis is incomplete and has prompted our interest to identify the type of effective osteogenic exercise. Objective: The aim of this study was to compare the changes in handgrip strength and bone metabolism after 6 ...

  10. Bone metabolism and hand grip strength response to aerobic versus ...

    African Journals Online (AJOL)

    Currently, our understanding of how to use exercise effectively in diabetic patients in prevention of osteo- porosis is incomplete and has prompted our interest to identify the type of effective osteogenic exercise. Objective: The aim of this study was to compare the changes in handgrip strength and bone metabolism after 6 ...

  11. Metabolic responses of alfalfa ( Medicago Sativa L.) leaves to low ...

    African Journals Online (AJOL)

    To explore adaptation mechanism of alfalfa to cold and heat stresses, status of sucrose metabolism and relative water content (RWC) in leaves under low and high temperature treatments were studied. Seedlings (35 day old) were transferred to chambers for treatments. First group was subjected to 5°C as low temperature ...

  12. Opposite metabolic responses of shoots and roots to drought

    Czech Academy of Sciences Publication Activity Database

    Gargallo-Garriga, A.; Sardans, J.; Pérez-Trujillo, M.; Rivas-Ubach, A.; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Jentsch, A.; Kreyling, J.; Beierkuhnlein, C.; Parella, T.; Penuelas, J.

    2014-01-01

    Roč. 4, č. 6829 (2014), s. 1-7 ISSN 2045-2322 Grant - others:AV ČR(CZ) M200871201 Institutional support: RVO:67179843 Keywords : shoot and roots * autotrophic and heterotrophic organs * environmental change * growth metabolism * water and nutirens Subject RIV: EH - Ecology, Behaviour Impact factor: 5.578, year: 2014

  13. ''Ecstasy''-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology. A 18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Schreckenberger, M.; Sabri, O.; Arning, C.; Zimny, M.; Zeggel, T.; Wagenknecht, G.; Kaiser, H.J.; Buell, U. [Technische Hochschule Aachen (Germany). Klinik fuer Nuklearmedizin; Gouzoulis-Mayfrank, E.; Sass, H. [Technische Hochschule Aachen (Germany). Dept. of Psychiatry

    1999-12-01

    The aim of this study was to determine the acute effects of the 'Ecstasy' analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a radomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose ({sup 18}FDG) positron emission tomography (PET) 110-120 min after oral administration of 2 mg/kg MDE (n=7) or placebo (n=8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using T1-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMR-Glu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed significantly decreased rMRGlu in the bilateral frontal cortex: left frontal posterior (-7.1%, P<0.05) and right prefrontal superior (-4.6%, P<0.05). On the other hand, rMR-Glu was significantly increased in the bilateral cerebellum (right: +10.1%, P<0.05; left: +7.6%, P<0.05) and in the right putamen (+6.2%, P<0.05). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r=0.87; P<0.05), both the right amygadala (r=0.90, P<0.01) and the left posterior cingulate (r=0.90, P<0.01) to difficulties in abstract thinking, and the right frontal inferior (r=0.85, P<0.05), right anterior cingulate (r=0.93, P<0.01), and left anterior cingulate (r=0.85, P<0.05) to attentional deficits. A

  14. Muscle metabolic remodelling in response to endurance exercise in salmonids

    Directory of Open Access Journals (Sweden)

    Andrea J Morash

    2014-11-01

    Full Text Available Phenotypic plasticity of skeletal muscle is relevant to swimming performance and metabolism in fishes, especially those that undergo extreme locomotory feats, such as seasonal migration. However, the influence of endurance exercise and the molecular mechanisms coordinating this remodelling are not well understood. The present study examines muscle metabolic remodelling associated with endurance exercise in fed rainbow trout as compared to migrating salmon. Trout were swum for 4 weeks at 1.5BL/s, a speed similar to that of migrating salmon and red and white muscles were sampled after each week. We quantified changes in key enzymes in aerobic and carbohydrate metabolism (citrate synthase (CS, β-hydroxyacyl-CoA dehydrogenase (HOAD, hexokinase (HK and changes in mRNA expression of major regulators of metabolic phenotype (AMPK, PPARs and lipid (carnitine palmitoyltransferase, CPT I, protein (aspartate aminotransferase, AST and carbohydrate (HK oxidation pathways. After one week of swimming substantial increases were seen in AMPK and PPARα mRNA expression and of their downstream target genes, CPTI and HK in red muscle. However, significant changes in CS and HK activity occurred only after 4 weeks. In contrast, there were few changes in mRNA expression and enzyme activities in white muscle over the 4-weeks. Red muscle results mimic those found in migrating salmon suggesting a strong influence of exercise on red muscle phenotype. In white muscle, only changes in AMPK and PPAR expression were similar to that seen with migrating salmon. However, in contrast to exercise alone, in natural migration HK decreased while AST increased suggesting that white muscle plays a role in supplying fuel and intermediates possibly through tissue breakdown during prolonged fasting. Dissecting individual and potentially synergistic effects of multiple stressors will enable us to determine major drivers of the metabolic phenotype and their impacts on whole animal

  15. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response: e1002135

    National Research Council Canada - National Science Library

    Adam Bajgar; Katerina Kucerova; Lucie Jonatova; Ales Tomcala; Ivana Schneedorferova; Jan Okrouhlik; Tomas Dolezal

    2015-01-01

      Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system...

  16. Effects of body lipid content on the resting metabolic rate and postprandial metabolic response in the southern catfish Silurus meridionalis.

    Science.gov (United States)

    Luo, Yiping; Xie, Xiaojun

    2009-12-01

    We assessed the effects of body lipid content on the resting metabolic rate and specific dynamic action (SDA) of the southern catfish Silurus meridionalis. Obese and lean fish were obtained by feeding the fish with two different feeds at 27.5 degrees C for 4 weeks prior to the experiment. The fish were fed with experimental diets with a meal size of 4% by body mass. A continuous-flow respirometer was used to determine the oxygen consumption rate at 2-h intervals until the postprandial oxygen consumption rate had returned to the preprandial level. The body lipid content of the obese fish was significantly greater than that of the lean fish. The metabolic parameters evaluated (resting metabolic rate, peak metabolic rate (R(peak)), factorial ratio, time to peak, duration, energy expended on SDA (SDA(E)), or SDA coefficient) were not significantly affected by body fat content in terms of the whole-body or mass-specific values. Increased body fat content did not decrease the resting metabolic rate in the southern catfish, which might be due to the higher levels of highly unsaturated fatty acids in these fish. The results also suggest that the body composition does not appear to affect the SDA response.

  17. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes

    NARCIS (Netherlands)

    Wopereis, S.; Rubingh, C.M.; van Erk, M.J.; Verheij, E.R.; van Vliet, T.; Cnubben, N.H.P.; Smilde, A.K.; van der Greef, J.; van Ommen, B.; Hendriks, H.F.J.

    2009-01-01

    Background: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one

  18. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans

    DEFF Research Database (Denmark)

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G

    2014-01-01

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle.......3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12-23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast...... venous noradrenaline, and falling arterial carbon dioxide tension (P aCO 2) (R(2) ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing P aCO 2 and enhancing vasoconstrictor activity. However...

  19. The structure of wheat bread influences the postprandial metabolic response in healthy men

    DEFF Research Database (Denmark)

    Eelderink, Coby; Noort, Martijn W J; Sozer, Nesli

    2015-01-01

    Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products...... or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products....

  20. In vivo metabolic imaging of mouse tumor models in response to chemotherapy

    Science.gov (United States)

    Lukina, Maria M.; Dudenkova, Varvara; Shumilova, Anastasia V.; Snopova, Ludmila B.; Zagaynova, Elena V.; Shirmanova, Marina V.

    2017-02-01

    The aim of the study was to estimate energy metabolism in human cervical cancer cells HeLa Kyoto after chemotherapy in vitro and in vivo using two-photon fluorescence lifetime microscopy (FLIM). Cellular metabolism was examined by monitoring of the fluorescence intensities and lifetimes of metabolic cofactors NAD(P)H and FAD. Cancer metabolism was analyzed in dynamics after treatment with cisplatin. Two-photon fluorescence and second harmonic generation microscopies as well as standard histopathology with hematoxylin and eosin were used to characterize cancer tissue structure. We showed an increase of the optical redox ratio FAD/NAD(P)H in cancer cells in vitro and decrease of the relative contribution of free NAD(P)H (ɑ1) in vitro and in vivo, which presumably indicate a shift to more oxidative metabolism after chemotherapy. These data demonstrate the possibility to detect response of cancer cells to chemotherapy using optical metabolic imaging.

  1. Cerebral blood volume response to changes in carbon dioxide tension before and during cardiopulmonary bypass in children, investigated by near infrared spectroscopy.

    Science.gov (United States)

    Fallon, P; Roberts, I G; Kirkham, F J; Edwards, A D; Lloyd-Thomas, A; Elliott, M J

    1994-01-01

    Neurological impairment may occur following cardiopulmonary bypass (CPB) and the effect of CPB on cerebrovascular control may be important in the mechanism of cerebral injury. We have used near infrared spectroscopy (NIRS) to observe cerebral haemodynamics non-invasively before and during CPB. We measured the change in cerebral blood volume (CBV) associated with changing PaCO2 (CBVR). Patients (n = 19) were aged from 1 to 135 (median 14) months. The cerebral blood volume response was determined pre-operatively at normothermia under the influence of standardised anaesthesia employing isoflurane (up to ET conc 0.5%) and during steady-state hypothermic bypass (22-32 degrees C) at an arterial pump flow rate of 1.9-2.4 lm-2.min-1. Complete data was available for 10 patients. The relation between CBV, arterial carbon dioxide tension (PaCO2), mean arterial pressure (MAP) and central venous pressure (CVP) was examined using analysis of covariance (P non-invasive technique for the investigation of cerebral haemodynamics during CPB.

  2. Cerebral Palsy

    Science.gov (United States)

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  3. Detection of synchronous gastric schwannoma on FDG PET/CT aided by discordant metabolic response.

    Science.gov (United States)

    Yap, June; Huang, Yi-Tung Tom; Lin, Michael

    2015-05-01

    This is a case of an unsuspected synchronous gastric schwannoma demonstrating increased F-FDG accumulation on PET/CT in a 65-year-old female patient diagnosed with non-Hodgkin lymphoma on the basis of different metabolic activity to other sites of disease at staging and discordant metabolic response to therapy. The gastric schwannoma was confirmed by histopathology and immunohistochemistry after surgical resection. This case adds to the limited literature on FDG-avid gastric schwannoma and highlights the importance of investigating differential metabolic activity and response on serial PET/CT imaging.

  4. Metabolic and cellular stress responses of catfish, Horabagrus brachysoma (Günther) acclimated to increasing temperatures.

    Science.gov (United States)

    Dalvi, Rishikesh S; Das, Tilak; Debnath, Dipesh; Yengkokpam, Sona; Baruah, Kartik; Tiwari, Lalchand R; Pal, Asim K

    2017-04-01

    We investigated the metabolic and cellular stress responses in an endemic catfish Horabagrus brachysoma acclimated to ambient (26°C), 31, 33 and 36°C for 30 days. After acclimation, fish were sampled to investigate changes in the levels of blood glucose, tissue glycogen and ascorbic acid, activities of enzymes involved in glycolysis (LDH), citric acid cycle (MDH), gluconeogenesis (FBPase and G6Pase), pentose phosphate pathway (G6PDH), protein metabolism (AST and ALT), phosphate metabolism (ACP and ALP) and energy metabolism (ATPase), and HSP70 levels in various tissues. Acclimation to higher temperatures (33 and 36°C) significantly increased activities of LDH, MDH, ALP, ACP, AST, ALT and ATPase and blood glucose levels, whereas decreased the G6PDH enzyme activity and, tissue glycogen and ascorbic acid. Results indicated an overall increase in the carbohydrate, protein and lipid metabolism implying increased metabolic demands for maintaining homeostasis in fish acclimated to higher temperatures (33 and 36°C). We observed tissue specific response of HSP70 in H. brachysoma, with significant increase in gill and liver at 33 and 36°C, and in brain and muscle at 36°C, enabling cellular protection at higher acclimation temperatures. In conclusion, H. brachysoma adjusted metabolic and cellular responses to withstand increased temperatures, however, these responses suggest that the fish was under stress at 33°C or higher temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Metabolic response of Agrobacterium tumefaciens 5A to arsenite.

    Science.gov (United States)

    Tokmina-Lukaszewska, Monika; Shi, Zunji; Tripet, Brian; McDermott, Timothy R; Copié, Valérie; Bothner, Brian; Wang, Gejiao

    2017-02-01

    Wide-spread abundance in soil and water, coupled with high toxicity have put arsenic at the top of the list of environmental contaminants. Early studies demonstrated that both concentration and the valence state of inorganic arsenic (arsenite, As(III) vs. arsenate As(V)) can be modulated by microbes. Using genetics, transcriptomic and proteomic techniques, microbe-arsenic detoxification, respiratory As(V) reduction and As(III) oxidation have since been examined. The effect of arsenic exposure on whole-cell intracellular microbial metabolism, however, has not been extensively studied. We combined LC-MS and (1) H NMR to quantify metabolic changes in Agrobacterium tumefaciens (strain 5A) upon exposure to sub-lethal concentrations of As(III). Metabolomics analysis reveals global differences in metabolite concentrations between control and As(III) exposure groups, with significant perturbations to intermediates shuttling into and cycling within the TCA cycle. These data are most consistent with the disruption of two key TCA cycle enzymes, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Glycolysis also appeared altered following As(III) stress, with carbon accumulating as complex saccharides. These observations suggest that an important consequence of As(III) contamination in nature will be to alter microbial carbon metabolism at the microbial community level and thus has the potential to foundationally impact all biogeochemical cycles in the environment. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux

    OpenAIRE

    Grüne, Frank; Kazmaier, Stephan; Sonntag, Barbara; Stolker, Robert; Weyland, Andreas

    2014-01-01

    textabstractBACKGROUND:: Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. METHODS:: Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Mea...

  7. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: 1H-MRS study.

    Science.gov (United States)

    Artzi, Moran; Liberman, Gilad; Vaisman, Nachum; Bokstein, Felix; Vitinshtein, Faina; Aizenstein, Orna; Ben Bashat, Dafna

    2017-04-01

    Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy (1H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and 1H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra-three within the NAWM and one in the lesion area -4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD. 1H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.

  8. Chronic myeloid leukemia patients sensitive and resistant to imatinib treatment show different metabolic responses.

    Directory of Open Access Journals (Sweden)

    Jiye A

    Full Text Available The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML. However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML and patients resistant to imatinib (RCML had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA. In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.

  9. Systematic survey of the design, statistical analysis, and reporting of studies published in the 2008 volume of the Journal of Cerebral Blood Flow and Metabolism.

    Science.gov (United States)

    Vesterinen, Hanna M; Vesterinen, Hanna V; Egan, Kieren; Deister, Amelie; Schlattmann, Peter; Macleod, Malcolm R; Dirnagl, Ulrich

    2011-04-01

    Translating experimental findings into clinically effective therapies is one of the major bottlenecks of modern medicine. As this has been particularly true for cerebrovascular research, attention has turned to the quality and validity of experimental cerebrovascular studies. We set out to assess the study design, statistical analyses, and reporting of cerebrovascular research. We assessed all original articles published in the Journal of Cerebral Blood Flow and Metabolism during the year 2008 against a checklist designed to capture the key attributes relating to study design, statistical analyses, and reporting. A total of 156 original publications were included (animal, in vitro, human). Few studies reported a primary research hypothesis, statement of purpose, or measures to safeguard internal validity (such as randomization, blinding, exclusion or inclusion criteria). Many studies lacked sufficient information regarding methods and results to form a reasonable judgment about their validity. In nearly 20% of studies, statistical tests were either not appropriate or information to allow assessment of appropriateness was lacking. This study identifies a number of factors that should be addressed if the quality of research in basic and translational biomedicine is to be improved. We support the widespread implementation of the ARRIVE (Animal Research Reporting In Vivo Experiments) statement for the reporting of experimental studies in biomedicine, for improving training in proper study design and analysis, and that reviewers and editors adopt a more constructively critical approach in the assessment of manuscripts for publication.

  10. Role of endogenous ENaC and TRP channels in the myogenic response of rat posterior cerebral arteries.

    Directory of Open Access Journals (Sweden)

    Eok-Cheon Kim

    Full Text Available Mechanogated ion channels are predicted to mediate pressure-induced myogenic vasoconstriction in small resistance arteries. Recent findings have indicated that transient receptor potential (TRP channels and epithelial sodium channels (ENaC are involved in mechanotransduction. The purpose of this study was to investigate the role of TRP channels and ENaC in the myogenic response. Our previous study suggested that ENaC could be a component of the mechanosensitive ion channels in rat posterior cerebral arteries (PCA. However, the specific ion channel proteins mediating myogenic constriction are unknown. Here we found, for the first time, that ENaC interacted with TRPM4 but not with TRPC6 using immunoprecipitation and confocal microscopy.Treatment with a specific βENaC inhibitor, amiloride, a specific TRPM4 inhibitor, 9-phenanthrol, and a TRPC6 inhibitor, SKF96365, resulted in inhibition of the pressure-induced myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with small interfering RNA of βENaC, TRPM4, and TRPC6. Co-treatment with amiloride and 9-phenanthrol showed a similar inhibitory effect on myogenic contraction compared to single treatment with amiloride or 9-phenanthrol. The myogenic response was not affected by 9-phenanthrol or amiloride treatment in PCA transfected with βENaC or TRPM4 siRNA, respectively. However, pressure-induced myogenic response was fully inhibited by co-treatment with amiloride, 9-phenanthrol, and SKF96365, and by treatment with SKF96365 in PCA transfected with βENaC siRNA.Our results suggest that ENaC, TRPM4, and TRPC6 play important roles in the pressure-induced myogenic response, and that ENaC and TRPM4 interact in rat PCA.

  11. Cerebral malaria Malaria cerebral

    Directory of Open Access Journals (Sweden)

    Silvia Blair Trujillo

    2003-03-01

    Full Text Available Is the most common complication of P. falciparum malaria; nearly 90% of people who have suffered CM can recover without neurological problems. Currently there are four hypotheses that explain pathogenesis of CM: cytoadherence and sequestering of parasitized red blood cells to cerebral capillaries; rosette formation and parasitized red blood cells agglutination; production of cytokines and activation of second messengers and opening of the blood-brain barrier. However the main question remains to be answered; how the host-parasite interaction in the vascular space interferes transiently with cerebral function? Recently, the beta amyloid precursor peptide has been employed as marker of neural injury in CM. It is expected that the beta amyloid precursor peptide will help to understand the pathogenesis of CM in complicated patients of endemic areas of Colombia. La malaria Cerebral (MC es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1 citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2 formación de rosetas y aglutinación de glóbulos rojos parasitados; 3 producción de citoquinas y activación de segundos mensajeros y, 4 apertura de la barrera hematoencefálica. Sin embargo, queda un interrogante sin resolver aún: ¿qué proceso se lleva a cabo para que el parásito, desde el espacio microvascular, pueda interferir transitoriamente con la función cerebral? Recientemente se ha utilizado el precursor de la proteína b-Amiloide como un marcador de daño neuronal en MC; este precursor será de gran ayuda en futuras investigaciones realizadas en nuestro medio que aporten información para comprender la patogénesis de la MC.

  12. Dealing with hunger: Metabolic stress responses in tumors

    Directory of Open Access Journals (Sweden)

    Michael A Reid

    2013-01-01

    Full Text Available Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  13. Dealing with hunger: Metabolic stress responses in tumors.

    Science.gov (United States)

    Reid, Michael A; Kong, Mei

    2013-09-30

    Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  14. Acquired cerebral dyschromatopsia.

    Science.gov (United States)

    Green, G J; Lessell, S

    1977-01-01

    Color blindness developed in five patients apparently because of lesions in the posterior portions of both cerebral hemispheres. Three of them also had symptoms of prosopagnosia. The lesions were neoplastic in two and vascular in three of the patients. It would appear that bilateral, inferior, occipital lobe lesions may be responsible both for acquired cerebral dyschromatopsia and prosopagnosia. Evidence from experimental investigations in primates suggests that the areas of the cerebral hemispheres analogous to those involved in these patients, may be specialized for the processing of colored stimuli.

  15. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Chu Ketan

    2012-04-01

    Full Text Available Abstract Background Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R injury. The P2X7 receptor (P2X7R has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Methods Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG, adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL. In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. Results The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg and A-0438079 (3 μg, and a low dosage of OxATP (1 μg significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Conclusions Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of

  16. Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.

    Science.gov (United States)

    Kaakinen, Timo; Heikkinen, Janne; Dahlbacka, Sebastian; Alaoja, Hanna; Laurila, Päivi; Kiviluoma, Kai; Salomäki, Timo; Romsi, Pekka; Tuominen, Hannu; Biancari, Fausto; Lepola, Pasi; Nuutinen, Matti; Juvonen, Tatu

    2006-01-01

    Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049). The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

  17. In-vitro investigation of the hemodynamic responses of the cerebral, coronary and renal circulations with a rotary blood pump installed in the descending aorta.

    Science.gov (United States)

    Rezaienia, M A; Paul, G; Avital, E J; Mozafari, S; Rothman, M; Korakianitis, T

    2017-02-01

    This study investigates the hemodynamic responses of the cardiovascular system when a rotary blood pump is operating in the descending aorta, with a focus on the cerebral, coronary and renal autoregulation, using our in-house cardiovascular emulator. Several improvements have been made from our previous studies. A novel coronary system was developed to replicate the native coronary perfusion. Three pinch valves actuated by stepper motors were used to simulate the regional autoregulation systems of the native cerebral, coronary and renal circulations. A rotary pump was installed in the descending aorta, in series with the heart, and the hemodynamic responses of the cardiovascular system were investigated with a focus on cerebral, coronary and renal circulation over a wide range of pump rotor speeds. Experiments were performed twice, once with the autoregulation systems active and once with the autoregulation systems inactive, to reflect that there will be some impairment of autoregulatory systems in a patient with heart failure. It was shown that by increasing the rotor speed to 3000 rpm, the cardiac output was improved from 2.9 to 4.1 L/min as a result of an afterload reduction induced by the pressure drop upstream of the pump. The magnitudes of changes in perfusion in the cerebral, coronary and renal circulations were recorded with regional autoregulation systems active and inactive. Copyright © 2016. Published by Elsevier Ltd.

  18. Effects of Dopamine Infusion on Cerebral Blood Flow, Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

    National Research Council Canada - National Science Library

    Park, Won Soon; Chang, Yun Sil; Shim, Jae Won; Kim, Mi Jung; Ko, Sun Young; Kim, Sung Shin; Hwang, Jong Hee; Choi, Chang Won; Lee, Munhyang

    2003-01-01

    .... The decreased cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain damage, were significantly attenuated by dopamine infusion...

  19. Cerebral hemodynamic responses to seizure in the mouse brain: simultaneous near-infrared spectroscopy-electroencephalography study

    Science.gov (United States)

    Lee, Seungduk; Lee, Mina; Koh, Dalkwon; Kim, Beop-Min; Choi, Jee Hyun

    2010-05-01

    We applied near-infrared spectroscopy (NIRS) and electroencephalography (EEG) simultaneously on the mouse brain and investigated the hemodynamic response to epileptic episodes under pharmacologically driven seizure. γ-butyrolactone (GBL) and 4-aminopyridine (4-AP) were applied to induce absence and tonic-clonic seizures, respectively. The epileptic episodes were identified from the single-channel EEG, and the corresponding hemodynamic changes in different regions of the brain were characterized by multichannel frequency-domain NIRS. Our results are the following: (i) the oxyhemoglobin level increases in the case of GBL-treated mice but not 4-AP-treated mice compared to the predrug state; (ii) the dominant response to each absence seizure is a decrease in deoxyhemolobin; (iii) the phase shift between oxy- and deoxyhemoglobin reduces in GBL-treated mice but no 4-AP-treated mice; and (iv) the spatial correlation of hemodynamics increased significantly in 4-AP-treated mice but not in GBL-treated mice. Our results shows that spatiotemporal tracking of cerebral hemodynamics using NIRS can be successfully applied to the mouse brain in conjunction with electrophysiological recording, which will support the study of molecular, cellular, and network origin of neurovascular coupling in vivo.

  20. Kinematic and EMG Responses to Pelvis and Leg Assistance Force during Treadmill Walking in Children with Cerebral Palsy

    Science.gov (United States)

    Kim, Janis; Arora, Pooja; Zhang, Yunhui

    2016-01-01

    Treadmill training has been used for improving locomotor function in children with cerebral palsy (CP), but the functional gains are relatively small, suggesting a need to improve current paradigms. The understanding of the kinematic and EMG responses to forces applied to the body of subjects during treadmill walking is crucial for improving current paradigms. The objective of this study was to determine the kinematics and EMG responses to the pelvis and/or leg assistance force. Ten children with spastic CP were recruited to participate in this study. A controlled assistance force was applied to the pelvis and/or legs during stance and swing phase of gait through a custom designed robotic system during walking. Muscle activities and spatial-temporal gait parameters were measured at different loading conditions during walking. In addition, the spatial-temporal gait parameters during overground walking before and after treadmill training were also collected. Applying pelvis assistance improved step height and applying leg assistance improved step length during walking, but applying leg assistance also reduced muscle activation of ankle flexor during the swing phase of gait. In addition, step length and self-selected walking speed significantly improved after one session of treadmill training with combined pelvis and leg assistance. PMID:27651955

  1. High-Resolution Radioluminescence Microscopy for the Study of Prostate Tissue Slice Cell Metabolism and Monitoring of Treatment Response

    Science.gov (United States)

    2015-09-01

    et al. (1982). Glucose utilization of cerebral gliomas measured by 18F-fluorodeoxyglucose and positron emission tomography. Neurol. 32(12):1323...a few cells) image of the local metabolism in prostate cancer tissue slice cultures (TSCs). Our hypothesis is that the local glucose concentration in...the prostate tissue in such a way that cancer cells use more glucose than normal cells [1,2]. This effect is exploited in positron emission

  2. Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux

    NARCIS (Netherlands)

    F. Grüne (Frank); S. Kazmaier (Stephan); B. Sonntag (Barbara); R.J. Stolker (Robert); A. Weyland (Andreas)

    2014-01-01

    textabstractBACKGROUND:: Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair

  3. Patient-specific determinants of responsiveness to robot-enhanced treadmill therapy in children and adolescents with cerebral palsy.

    Science.gov (United States)

    Schroeder, Andreas Sebastian; Von Kries, Rüdiger; Riedel, Christina; Homburg, Maria; Auffermann, Helene; Blaschek, Astrid; Jahn, Klaus; Heinen, Florian; Borggraefe, Ingo; Berweck, Steffen

    2014-12-01

    The aim of the study was to evaluate patient-specific determinants of responsiveness to robot-enhanced repetitive treadmill therapy (ROBERT) in patients with early-developed movement disorders. Patients were treated over 12 sessions during a 3-week period. Gross Motor Function Measure-66 (GMFM-66) scores 1 day before ROBERT were compared with scores recorded 1 day after ROBERT. The association of GMFM-66 baseline score, age, sex, aetiology, and add-on botulinum toxin therapy to response to treatment was assessed. Eighty-three patients aged between 4 and 18 years (48 males, 35 females; mean age 10y 8mo, SD 6y 1mo; Gross Motor Function Classification System level I [n=12], II [n=21], III [n=35], IV [n=10], and V [n=1]) were each treated for a total of 7.2 (SD 1.9) treadmill walking hours. Aetiology was bilateral spastic cerebral palsy (BS-CP; n=69), unilateral CP (n=3), ataxic CP (n=3), hereditary spastic paraparesis (n=6), and genetic syndrome including spasticity (n=2). Meaningful improvements were observed in GMFM-66 (+2.5; 95% CI 2.0-3.0), GMFM-D (+5.2; 95% CI 3.6-6.8), and GMFM-E (+4.0; 95% CI 2.8-5.3). There was a high inter-individual variability in treatment response. After multivariable adjustment, the improvements in GMFM-66 and GMFM-E scores were positively associated with the GMFM-66 baseline score. The effect on GMFM-D improvement was inversely associated with age. Gross motor abilities at baseline and age were identified as relevant determinants for the high degree of interpersonal variability in response to ROBERT. © 2014 Mac Keith Press.

  4. Variations in metabolic responses to meal challenges differing in glycemic index in healthy women: Is it meaningful?

    Science.gov (United States)

    Background: Metabolic phenotyping has potential utility as a diagnostic tool. While clinical parameters are commonly used in disease diagnosis, tools that enhance diagnosis of metabolic dysfunctions are needed. Objective: To identify typical and atypical metabolite temporal patterns in response t...

  5. Variation in metabolic responses to meal challenges differing in glycemic index in healthy women: Is it meaningful?

    Science.gov (United States)

    Background: Metabolic phenotyping has potential utility as a diagnostic tool. While clinical parameters are commonly used in disease diagnosis, tools that enhance diagnosis of metabolic dysfunctions are needed. Objective: To identify typical and atypical metabolite temporal patterns in response to ...

  6. Response to Cardiac Resynchronization Therapy: The Muscular Metabolic Pathway

    Directory of Open Access Journals (Sweden)

    Jérémie Jaussaud

    2011-01-01

    245±140 seconds (=.01. Peak VO2, VE/VCO2, peak circulatory power and NYHA were improved after CRT (13±4 to16±5 ml/kg/min (<.05, 45±16 to 39±13 (<.01, 1805±844 to 2225±1171 mmHg.ml/kg/min (<.01 and 3±0.35 to 1.88±0.4 (=.01. In addition, left ventricular ejection fraction and end-systolic volumes were improved from 24±8 to 29±7% (<.01 and from 157±69 to 122±55 ml (<.01. Conclusion. We suggest that CRT leads to an increase in oxidative muscular metabolism and postponed anaerobic threshold reducing exaggerated hyperventilation during exercise.

  7. Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

    DEFF Research Database (Denmark)

    Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

    2016-01-01

    OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release...... of stress hormones. We compared the metabolic effects of LPS in hypopituitary patients (HP) (in the absence of pituitary stress hormone responses) and healthy control subjects (CTR) (with normal pituitary stress hormone responses). DESIGN: Single blind randomized. METHODS: We compared effects of LPS...

  8. Metabolic responses of the South American ornate horned frog (Ceratophrys ornata) to estivation.

    Science.gov (United States)

    Groom, Derrick J E; Kuchel, Louise; Richards, Jeffrey G

    2013-01-01

    We examined the metabolic responses of the South American frog, Ceratophrys ornata, to laboratory-induced estivation. Whole-animal and mass-specific oxygen consumption rates (VO(2)) did not change during fasting or 56days of estivation, despite observing significant decreases in body mass. The maintenance of mass-specific metabolic rate at routine levels during estivation suggests that metabolic rate suppression is not a major response to estivation in this species. There was a significant decline in liver glycogen and a loss of adipose tissue mass during estivation, suggesting that both carbohydrate and lipid pathways are used to fuel metabolism during estivation. The activity of pyruvate dehydrogenase, an important regulator of carbohydrate oxidation, and carnitine palmitoyltransferase and 3-hydroxyacyl-CoA dehydrogenase, regulators of lipid oxidation, showed no significant change in activity in liver, heart, and muscle between estivating and active frogs. There was an increase in plasma osmolality, which is characteristic of estivating animals. Overall, our metabolic analysis of estivation in C. ornata indicates that this species does not employ a dramatic suppression metabolic rate to survive dehydration stress and that both endogenous carbohydrates and lipids are used as metabolic fuels. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Alterations in local cerebral metabolic rates for glucose (LCMRGlc) in childhood epilepsies as determined with FDG and PET

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Chugani, H.T.; Mazziotta, J.C.; Engel, Jr.

    1985-05-01

    The authors investigated LCMRGlc in Lennox-Gastant Syndrome (LGS) (n=15), infantile spasm (IS) (n=14) and Sturge-Weber Syndrome (SWS) (n=5). In children with LGS, 3 distinct metabolic patterns are seen interically: 1) unilateral focal hypometabolism in frontal or temporal lobes, 2) unilateral diffuse hypometabolism, and 3) bilateral diffuse hypometabolism. Therapeutic implications of this classification are: surgical resection in focal (i.e., as for partial epilepsy), corpus callosotomy in diffuse unilateral, and elimination of surgery for those with bilateral diffuse hypometabolism. Babies with idiopathic IS showed symmetrical hypometabolism of lenticular nuclei and midbrain/brain stem compared to cortex and is characterized by slightly better prognosis. In contrast, babies with symtomatic IS had additional CMRGlc disturbances such as bilateral assymetric and multi focal hypometabolism in infant with neurofibromatosis; right parieto-occipital hypometabolims in infant with tuberous sclerosis; intense hypermetabolism of hypothalamus (34.5 vs 3.18 ..mu..moles/-min/100g in other regions) in another where x-ray CT showed only obstructive hydrocephalus. Findings support classical notion of subcortical involvement in this disorder. In SWS, PET showed marked hypometabolism in affected hemisphere in older children, while a 9 month old showed increased LCMRGlc unilaterally (40-50 vs 28-44 ..mu.. moles/min/100g contralateral) with cross cerebellar hypermetabolism (48-50 vs 27-31 ..mu.. moles/min/100g) with no behavioral or EEG evidence of seizure during study. PET studies of LCMRGlc appear sensitive and useful in classifying heterogeneous syndromes into subtypes regarding differential therapy and prognosis, and provide more comprehensive identification of sites of disturbance for investigating mechanisms of these disorders.

  10. Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine

    DEFF Research Database (Denmark)

    Friberg, L; Olesen, Jes; Lassen, N A

    1994-01-01

    The aura phase of migraine is associated with focal blood flow changes, but it has been largely unknown whether these changes are correlated to changes in the cerebral metabolism.......The aura phase of migraine is associated with focal blood flow changes, but it has been largely unknown whether these changes are correlated to changes in the cerebral metabolism....

  11. Metabolic and adaptive immune responses induced in mice infected ...

    African Journals Online (AJOL)

    Tissue-dwelling helminths are known to induce intestinal and systemic inflammation accompanied with host compensatory mechanisms to counter balance ... Furthermore, we showed for the first time that non-encapsulated T. zimbabwensis parasite plays a role in immunomodulating host Th1/Th17 type responses during ...

  12. Metabolic responses of alfalfa (Medicago Sativa L.) leaves to low ...

    African Journals Online (AJOL)

    user

    2011-02-14

    Feb 14, 2011 ... Aranjuelo I, Irigoyen JJ, Perez P, Martinez-Carrasco R, Sanchez-Diaz. M (2006). Response of nodulated alfalfa to water supply, temperature and elevated CO2: productivity and water relations. Environ. Exp. Bot. 55: 130-141. Aranjuelo I, Irigoyen JJ, Sanchez-Diaz M (2007). Effect of elevated temperature ...

  13. Probing soil C metabolism in response to temperature: results from experiments and modeling

    Science.gov (United States)

    Dijkstra, P.; Dalder, J.; Blankinship, J.; Selmants, P. C.; Schwartz, E.; Koch, G. W.; Hart, S.; Hungate, B. A.

    2010-12-01

    C use efficiency (CUE) is one of the least understood aspects of soil C cycling, has a very large effect on soil respiration and C sequestration, and decreases with elevated temperature. CUE is directly related to substrate partitioning over energy production and biosynthesis. The production of energy and metabolic precursors occurs in well-known processes such as glycolysis and Krebs cycle. We have developed a new stable isotope approach using position-specific 13C-labeled metabolic tracers to measure these fundamental metabolic processes in intact soil communities (1). We use this new approach, combined with models of soil metabolic flux patterns, to analyze the response of microbial energy production, biosynthesis, and CUE to temperature. The method consists of adding small but precise amounts of position-specific 13C -labeled metabolic tracers to parallel soil incubations, in this case 1-13C and 2,3-13C pyruvate and 1-13C and U-13C glucose. The measurement of CO2 released from the labeled tracers is used to calculate the C flux rates through various metabolic pathways. A simplified metabolic model consisting of 23 reactions is iteratively solved using results of the metabolic tracer experiments and information on microbial precursor demand under different temperatures. This new method enables direct study of fundamental aspects of microbial energy production, C use efficiency, and soil organic matter formation in response to temperature. (1) Dijkstra P, Blankinship JC, Selmants PC, Hart SC, Koch GW, Schwarz E and Hungate BA. Probing metabolic flux patterns of soil microbial communities using parallel position-specific tracer labeling. Soil Biology and Biochemistry (accepted)

  14. The Response to 2-Aminoacrylate Differs in Escherichia coli and Salmonella enterica, despite Shared Metabolic Components.

    Science.gov (United States)

    Borchert, Andrew J; Downs, Diana M

    2017-07-15

    The metabolic network of an organism includes the sum total of the biochemical reactions present. In microbes, this network has an impeccable ability to sense and respond to perturbations caused by internal or external stimuli. The metabolic potential (i.e., network structure) of an organism is often drawn from the genome sequence, based on the presence of enzymes deemed to indicate specific pathways. Escherichia coli and Salmonella enterica are members of the Enterobacteriaceae family of Gram-negative bacteria that share the majority of their metabolic components and regulatory machinery as the "core genome." In S. enterica, the ability of the enamine intermediate 2-aminoacrylate (2AA) to inactivate a number of pyridoxal 5'-phosphate (PLP)-dependent enzymes has been established in vivo In this study, 2AA metabolism and the consequences of its accumulation were investigated in E. coli The data showed that despite the conservation of all relevant enzymes, S. enterica and E. coli differed in both the generation and detrimental consequences of 2AA. In total, these findings suggest that the structure of the metabolic network surrounding the generation and response to endogenous 2AA stress differs between S. enterica and E. coliIMPORTANCE This work compared the metabolic networks surrounding the endogenous stressor 2-aminoacrylate in two closely related members of the Enterobacteriaceae The data showed that despite the conservation of all relevant enzymes in this metabolic node, the two closely related organisms diverged in their metabolic network structures. This work highlights how a set of conserved components can generate distinct network architectures and how this can impact the physiology of an organism. This work defines a model to expand our understanding of the 2-aminoacrylate stress response and the differences in metabolic structures and cellular milieus between S. enterica and E. coli. Copyright © 2017 American Society for Microbiology.

  15. Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Mostajeran, Maryam; Edvinsson, Lars

    2017-01-01

    receptor changes to be one of the injurious mechanisms occurring after stroke but mostly in healthy rats. The aim of this study was to investigate if hypertension has an effect on vasoconstrictive receptor responses to endothelin 1, sarafotoxin 6c and angiotensin II after stroke by inducing transient...

  16. Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Gulbenkian, Sergio; Engel, Ulla

    2004-01-01

    -hydroxytryptamine (5-HT) and the relaxant responses induced by acetylcholine (ACh), VIP and pituitary adenylate cyclase activating peptide-27 (PACAP) as well as CGRP and SP were compared in vitro. In conclusion, there was no major difference in innervation pattern or vasomotor sensitivity (pEC50 and pIC50 values...

  17. Metabolic reprogramming and apoptosis sensitivity: Defining the contours of a T cell response.

    Science.gov (United States)

    Voss, Kelsey; Larsen, Sasha E; Snow, Andrew L

    2017-11-01

    An effective adaptive immune response hinges on the rapid clonal expansion of T cells in response to antigen. The sensitivity of these T cells to programmed cell death (i.e. apoptosis) is carefully calibrated at various stages to ensure a robust yet measured reaction that resolves without inflicting unintended damage to host tissues. To meet bioenergetic demands associated with vigorous proliferation, acquisition of effector functions, and memory formation, T cells also undergo dynamic changes in their metabolism at every stage of this response. In this review, we focus on relatively recent studies that illuminate intimate links between metabolic programs and apoptosis sensitivity in T cells. We then examine how these connections ultimately influence T cell survival and function within the metabolically taxing environs of the tumor microenvironment. Published by Elsevier B.V.

  18. Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection.

    Science.gov (United States)

    Lamour, Sabrina D; Veselkov, Kirill A; Posma, Joram M; Giraud, Emilie; Rogers, Matthew E; Croft, Simon; Marchesi, Julian R; Holmes, Elaine; Seifert, Karin; Saric, Jasmina

    2015-01-02

    Parasitic infections such as leishmaniasis induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models. We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases.

  19. [Metabolic and immune response to spinal vs intravenous morphine for analgesia after radical prostatectomy].

    Science.gov (United States)

    Longás Valién, J; Abengochea Beisty, J M; Martínez Ubieto, J R; Giron Mombiela, J A; Rodríguez Zazo, A; Cuartero Lobera, J

    2005-12-01

    To study differences between the endocrine-metabolic and immune cell responses to spinal or intravenous administration of morphine for analgesia after radical prostatectomy. Prospective study of 60 patients randomized to 2 groups: in group A (n=30) morphine for postoperative analgesia was infused intravenously and in group B (n=30) morphine was infused into the spinal canal. Changes in leukocyte populations and lymphocyte subpopulations in peripheral blood and blood from surgical drains (local) were analyzed to study immune cell response to morphine administration. Cortisol, corticotropin, growth hormone, glucose, and immunoglobulin levels in peripheral blood were measured as indicators of metabolic and humoral immune responses. Both groups developed lymphopenia in peripheral blood. The group treated with spinal morphine had significantly lower CD4+ cell counts in peripheral blood Presponse in either group. Significant differences were found in natural killer and CD4+ cell counts both locally and in peripheral blood Pimmune response suppression in both groups; however, it was more marked in the group treated with spinal morphine and the difference was significant Pmetabolic response was greater in the group treated with intravenous morphine. Patients who received morphine by spinal infusion had a less marked endocrine-metabolic response. Although local cell responses were similar in the 2 groups, the response in peripheral blood was different, possibly reflecting different mechanisms of central modulation of the inflammatory response to stress.

  20. In vivo measurements of cerebral metabolic abnormalities by proton spectroscopy after a transient ischemic attack revealing an internal carotid stenosis > 70%; Anomalies metaboliques cerebrales mesurees in vivo par la spectroscopie du proton dans les accidents ischemiques transitoires revelant une stenose de la carotide interne superieure a 70%

    Energy Technology Data Exchange (ETDEWEB)

    Giroud, M.; Becker, F.; Lemesle, M.; Walker, P.; Guy, F.; Martin, D.; Baudouin, N.; Brunotte, F.; Dumas, R. [Centre Hospitalier Universitaire, 21 -Dijon (France)

    1996-06-01

    Aims: The aim of this work is to look for cerebral metabolic abnormalities within the first 3 days after a transient ischemic attack revealing an internal carotid stenosis > 70 %. Methods: Five patients with a transient ischemic attack lasting between 30 and 180 minutes, affecting sensory and motor brachio-facial territory, with or without aphasia. Were studied. A CT-scan, an EEG, a cervical Doppler ultrasound, a standard arteriography, a magnetic resonance imaging and a proton spectroscopy were performed within the cerebral area affected by the transient ischemic attack. We measured 2 markers: N-acetyl-aspartate, the marker of the neuronal mass, and lactate, the marker of anaerobe metabolism. In each case, a contralateral internal stenosis was diagnosed by cervical Doppler ultrasound and standard arteriography. No cerebral infarction was observed. Results: With the affected cerebral area defined according to clinical and EEG features, proton spectroscopy showed a significant rise of lactate, without any change in N-acetyl-aspartate levels. Conclusions: Within the first 3 days after a transient ischemic attack, there is a significant risk of lactate inside the affected cerebral area. This change may reflect a localized and transient hypoperfusion, but long enough to induce a rise of lactate but not sufficient to produce a cerebral infarct. This area is probably at risk to induce cerebral infarct. This data lead us to study the metabolic change induced by the asymptomatic internal carotid stenosis. (authors). 18 refs.

  1. Deep Ocean Mineral Supplementation Enhances the Cerebral Hemodynamic Response during Exercise and Decreases Inflammation Postexercise in Men at Two Age Levels

    Directory of Open Access Journals (Sweden)

    Ching-Yin Wei

    2017-12-01

    Full Text Available Background: Previous studies have consistently shown that oral supplementation of deep ocean minerals (DOM improves vascular function in animals and enhances muscle power output in exercising humans.Purpose: To examine the effects of DOM supplementation on the cerebral hemodynamic response during physical exertion in young and middle-aged men.Design: Double-blind placebo-controlled crossover studies were conducted in young (N = 12, aged 21.2 ± 0.4 years and middle-aged men (N = 9, aged 46.8 ± 1.4 years. The counter-balanced trials of DOM and Placebo were separated by a 2-week washout period. DOM and Placebo were orally supplemented in drinks before, during, and after cycling exercise. DOM comprises desalinated minerals and trace elements from seawater collected ~618 m below the earth's surface.Methods: Cerebral hemodynamic response (tissue hemoglobin was measured during cycling at 75% VO2max using near infrared spectroscopy (NIRS.Results: Cycling time to exhaustion at 75% VO2max and the associated plasma lactate response were similar between the Placebo and DOM trials for both age groups. In contrast, DOM significantly elevated cerebral hemoglobin levels in young men and, to a greater extent, in middle-aged men compared with Placebo. An increased neutrophil to lymphocyte ratio (NLR was observed in middle-aged men, 2 h after exhaustive cycling, but was attenuated by DOM.Conclusion: Our data suggest that minerals and trace elements from deep oceans possess great promise in developing supplements to increase the cerebral hemodynamic response against a physical challenge and during post-exercise recovery for middle-aged men.

  2. Contractile responses to ergotamine and dihydroergotamine in the perfused middle cerebral artery of rat

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Nilsson, Elisabeth; Edvinsson, Lars

    2007-01-01

    , with pEC(50) values of 7.6+/-0.2 for ergotamine and 8.4+/-0.5 for DHE. The responses were blocked by the 5-HT(2A) receptor antagonist ketanserin (concentration 10(-12) to 10(-5) M) and partially with the 5-HT(1B) receptor antagonist BRL-11557PM-B. The 5-HT(1D) receptor antagonist SB-224289-A had...... no significant effect. Using a myograph technique, isolated ring segments of the MCA with intact endothelium were mounted on two metal wires. Neither agonist caused relaxation of resting vessels, however, they both responded by weak contractile responses (26+/-3% of submaximal contractile capacity relative to 60...

  3. Frontal cerebral oxygen response as an indicator of initial attention effort during perceptual learning.

    Science.gov (United States)

    Ong, Michael; Russell, Paul N; Helton, William S

    2013-09-01

    Perceptual learning is critical in many settings. In the present study, we investigated the role of individual differences in attention effort in perceptual learning by having participants learn to detect rare cryptic figures. We employed both functional near-infrared spectroscopy measures of frontal cortical activity and self-reports of pre-task motivation in order to assess individual differences in attention effort. We also manipulated performance feedback and the amount of background information provided to the participants regarding the task. Twelve men and 28 women participated in the experiment. Performance metrics were indicative of perceptual learning occurring. Overall performance on the task was correlated significantly with pre-task levels of self-reported motivation and the rate of learning was correlated with initial oxygen response in the frontal cortex. The initial spike in frontal oxygen response declined with time on task, perhaps due to shifts towards automaticity. The results suggest perceptual learning is influenced by individual differences in attention effort.

  4. Pregnancy and pharmacogenomics in the context of drug metabolism and response.

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    Helldén, Anders; Madadi, Parvaz

    2013-11-01

    It is well-known that profound physiological and biochemical changes occur throughout the course of pregnancy. At the same time, the role of pharmacogenomics in modulating the metabolism and response profile to numerous medications has been elucidated. Yet, the clinical impact of pharmacogenomics during pregnancy is less well understood. We present an overview of factors modulating the pharmacokinetics and pharmacodynamics of medications throughout the time span of pregnancy while providing insights on how pharmacogenomics may contribute to interindividual variability in drug metabolism and response amongst pregnant women.

  5. Influence of the serotonin transporter promoter gene and shyness on children's cerebral responses to facial expressions.

    Science.gov (United States)

    Battaglia, Marco; Ogliari, Anna; Zanoni, Annalisa; Citterio, Alessandra; Pozzoli, Uberto; Giorda, Roberto; Maffei, Cesare; Marino, Cecilia

    2005-01-01

    Childhood shyness can predate social anxiety disorder and may be associated with biased discrimination of facial expressions of emotions. To determine whether childhood shyness, or the serotonin transporter promoter polymorphism genotype, can predict participants' visual event-related potentials in response to expressions of children of similar ages. Study group drawn from an inception cohort of 149 subjects characterized 1 year before the present study by their degree of shyness. Third- and fourth-grade schoolchildren. Forty-nine of the inception cohort children, randomly selected. Latencies and amplitudes of the N400 waveform in response to happy, neutral, and angry expressions. Shyness predicted significantly smaller N400 amplitudes in response to anger (at Pz: P Shyness was significantly different across the 3 genotypes, the SS genotype being associated with higher shyness levels (analysis of variance: F(2,42) = 4.47, P shyness or have 1 or 2 copies of the short allele of the serotonin transporter promoter gene appear to have a different pattern of processing affective stimuli of interpersonal hostility.

  6. Response inhibition is modulated by functional cerebral asymmetries for facial expression perception

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    Sebastian eOcklenburg

    2013-11-01

    Full Text Available The efficacy of executive functions is critically modulated by information processing in earlier cognitive stages. For example, initial processing of verbal stimuli in the language-dominant left-hemisphere leads to more efficient response inhibition than initial processing of verbal stimuli in the non-dominant right hemisphere. However, it is unclear whether this organizational principle is specific for the language system, or a general principle that also applies to other types of lateralized cognition. To answer this question, we investigated the neurophysiological correlates of early attentional processes, facial expression perception and response inhibition during tachistoscopic presentation of facial ‘Go’ and ‘Nogo’ stimuli in the left and the right visual field. Participants committed fewer false alarms after Nogo-stimulus presentation in the left compared to the right visual field. This right-hemispheric asymmetry on the behavioral level was also reflected in the neurophysiological correlates of face perception, specifically in a right-sided asymmetry in the N170 amplitude. Moreover, the right-hemispheric dominance for facial expression processing also affected event-related potentials typically related to response inhibition, namely the Nogo-N2 and Nogo-P3. These findings show that an effect of hemispheric asymmetries in early information processing on the efficacy of higher cognitive functions is not limited to left-hemispheric language functions, but can be generalized to predominantly right-hemispheric functions.

  7. [Response of arbuscular mycorrhizal fungal lipid metabolism to symbiotic signals in mycorrhiza].

    Science.gov (United States)

    Tian, Lei; Li, Yuanjing; Tian, Chunjie

    2016-01-04

    Arbuscular mycorrhizal (AM) fungi play an important role in energy flow and nutrient cycling, besides their wide distribution in the cosystem. With a long co-evolution, AM fungi and host plant have formed a symbiotic relationship, and fungal lipid metabolism may be the key point to find the symbiotic mechanism in arbusculart mycorrhiza. Here, we reviewed the most recent progress on the interaction between AM fungal lipid metabolism and symbiotic signaling networks, especially the response of AM fungal lipid metabolism to symbiotic signals. Furthermore, we discussed the response of AM fungal lipid storage and release to symbiotic or non-symbiotic status, and the correlation between fungal lipid metabolism and nutrient transfer in mycorrhiza. In addition, we explored the feedback of the lipolysis process to molecular signals during the establishment of symbiosis, and the corresponding material conversion and energy metabolism besides the crosstalk of fungal lipid metabolism and signaling networks. This review will help understand symbiotic mechanism of arbuscular mycorrhiza fungi and further application in ecosystem.

  8. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators.

    Science.gov (United States)

    Bedinger, Daniel H; Adams, Sean H

    2015-11-05

    Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic and mitogenic responses to insulin are regulated by divergent post-receptor signaling mechanisms downstream from the activated insulin receptor (IR). However, the anabolic and growth-promoting properties of insulin require tissue-specific inter-relationships between the two pathways, and the nature and scope of insulin-regulated processes vary greatly across tissues. Understanding the nuances of this interplay between metabolic and growth-regulating properties of insulin would have important implications for development of novel insulin and IR modulator therapies that stimulate insulin receptor activation in both pathway- and tissue-specific manners. This review will provide a unique perspective focusing on the roles of "metabolic" and "mitogenic" actions of insulin signaling in various tissues, and how these networks should be considered when evaluating selective pharmacologic approaches to prevent or treat metabolic disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Organization of sensory discrimination and response selection in choice and nonchoice conditions: a study using cerebral evoked potentials in normal humans.

    Science.gov (United States)

    Goodin, D S; Aminoff, M J; Shefrin, S L

    1990-10-01

    1. It has been suggested that the long-latency "event-related" cerebral evoked potentials (ERPs) reflect certain aspects of the neural processing underlying sensory discrimination in a two-choice reaction time task. The present paper examines the hypothesis that the coupling of these ERPs to sensory discrimination is variable and that the discrimination process is completed at different points during the course of cerebral processing, depending on the actual requirements of the task. 2. We recorded the cerebral evoked potentials and electromyogram (EMG) of the responding muscle in five different reaction time tasks, each requiring sensory discrimination and response selection of varying complexity. In the Choice condition two stimuli were presented, and two separate responses were required. In the two Go-No Go conditions two stimuli were presented, but a response was required to only one or the other of the stimuli. In the two Simple conditions only one stimulus was presented, and one response was required. 3. Under both Choice and Go-No Go conditions, the frequency histogram of the onset latency of the compound muscle action potential for the response to the frequent tone showed a bimodal distribution without overlap, suggesting that there were two distinct types of responder: fast and slow. The comparable histograms for the onset latency of the response to the rare tone also showed a bimodal distribution, but the mean onset latency was prolonged relative to the response to the frequent tone, and the mean separation was less so that the two distributions overlapped each other. 4. Despite the marked difference in response latencies between the fast and slow responders, there was no appreciable difference in cerebral evoked responses between the two groups. Moreover, in response to the frequent tone, all slow responders and, likewise, all fast responders had similar onset latencies of the averaged EMG activity regardless of condition. Nonetheless, fast or slow

  10. Alcohol sensitizes cerebral responses to the odors of alcoholic drinks: an fMRI study.

    Science.gov (United States)

    Bragulat, Veronique; Dzemidzic, Mario; Talavage, Thomas; Davidson, Dena; O'Connor, Sean J; Kareken, David A

    2008-07-01

    Small, priming doses of alcohol enhance desire to drink, and thus play a role in the loss of control of alcohol consumption. Using functional magnetic resonance imaging (fMRI), we previously showed that alcoholic drink odors (AO; subjects' drinks of choice) induce greater nucleus accumbens (NAc) activity than non-appetitive odors (NApO; grass, leather) in subjects at risk for alcoholism. Here we hypothesized that priming exposure to alcohol would enhance responses to AO in the NAc and orbitofrontal cortex in comparison to NApO (grass, leather) and to the appetitive control odors (ApCO) of chocolate and grape. Ten hazardous drinkers (mean age = 22.7; SD = 2.9, average drinks per drinking day = 5.9, SD = 2.3; drinking days/90 days = 50.4, SD = 13.7) were scanned on a 1.5 T GE Signa MR scanner during intravenous infusion of lactated Ringer's or 6% ethanol in lactated Ringer's that was pharmacokinetically modeled to achieve a constant breath alcohol concentration (BrAC) of 50 mg% throughout imaging. During scanning, subjects sniffed AO, NApO, and ApCO. Alcohol infusion enhanced the contrast between AO and NApO in the NAc, and in orbitofrontal, medial frontal, and precuneus/posterior cingulate regions. The contrast between AO and appetitive control odors (ApCO; chocolate and grape) was similarly larger in the orbital, medial frontal, precuneus, and posterior cingulate/retrosplenial areas, with the most robust finding being a potentiated response in the posterior cingulate/retrosplenial area. The orbital region is similar to an area previously shown to manifest satiety-related decreases in activity induced by food cues. The results suggest that priming exposure to alcohol renders a limbic network more responsive to alcohol cues, potentially enhancing desire to drink.

  11. Cytolytic T lymphocyte responses to metabolically inactivated stimulator cells. I. Metabolic inactivation impairs both CD and LD antigen signals

    Energy Technology Data Exchange (ETDEWEB)

    Kelso, A.; Boyle, W.

    1982-03-01

    The effects of metabolic inactivation of spleen cells on antigen presentation to precursors of alloreactive cytolytic T lymphocytes (T/sub c/) were examined. By serological methods, populations inactivated by ultraviolet irradiation, glutaraldehyde fixation or plasma membrane isolation were found to retain normal levels of H-2K/D and Ia antigens. However, comparison of the antigen doses required to stimulate secondary T/sub c/ responses in mixed leukocyte culture showed that the inactivated preparations were approximately 10-fold less immunogenic than X-irradiated spleen cells. Their total inability to stimulate primary cytolytic responses pointed to at least a 100-fold impairment of immunogenicity for unprimed T/sub c/ precursors in the case of uv-irradiated and glutaraldehyde-treated stimulator cells, and at least a 10-fold impairment for membrane fragments. Experiments showing that the capacity of cell monolayers to absorb precursor T/sub c/ from unprimed spleen populations was reduced following uv-irradiation or glutaraldehyde treatment provided direct evidence that this loss of immunogenicity was due in part to suboptimal antigen presentation to precursor T/sub c/. It is concluded that, in addition to the traditional view that these treatments damage the ''LD'' signal to helper T lymphocytes, metabolic inactivation also impairs recognition of ''CD'' determinants by precursor T/sub c/.

  12. Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy

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    Cao Maria D

    2012-01-01

    Full Text Available Abstract Background Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC, relating these changes to clinical treatment response and long-term survival. Methods Patients (n = 89 participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy. Biopsies were excised pre- and post-treatment, and analyzed by high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS. The metabolite profiles were examined by paired and unpaired multivariate methods and findings of important metabolites were confirmed by spectral integration of the metabolite peaks. Results All patients had a significant metabolic response to NAC, and pre- and post-treatment spectra could be discriminated with 87.9%/68.9% classification accuracy by paired/unpaired partial least squares discriminant analysis (PLS-DA (p p = 0.004 after treatment, while survivors (≥ 5 years experienced a decrease in the levels of glycine (p = 0.047 and choline-containing compounds (p ≤ 0.013 and an increase in glucose (p = 0.002 levels. The metabolic responses were not related to clinical treatment response. Conclusions The differences in tumor metabolic response to NAC were associated with breast cancer survival, but not to clinical response. Monitoring metabolic responses to NAC by HR MAS MRS may provide information about tumor biology related to individual prognosis.

  13. Regional brain metabolic response to lorazepam in alcoholics during early and late alcohol detoxification.

    Science.gov (United States)

    Volkow, N D; Wang, G J; Overall, J E; Hitzemann, R; Fowler, J S; Pappas, N; Frecska, E; Piscani, K

    1997-10-01

    Changes in GABA function have been postulated to be involved in alcohol tolerance, withdrawal and addiction. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission), in alcoholics during early and late withdrawal. Brain metabolism was measured using PET and 2-deoxy-2[18F]fluoro-D-glucose after placebo (baseline) and after lorazepam (30 micrograms/kg intravenously) in 10 alcoholics and 16 controls. In the alcoholics evaluations were performed 2 to 3 weeks after detoxification and were repeated 6 to 8 weeks later. Controls were also evaluated twice at a 6 to 8 weeks interval. While during the initial evaluation metabolism was significantly lower for most brain regions in the alcoholics than in controls in the repeated evaluation the only significant differences were in cingulate and orbitofrontal cortex. Lorazepam-induced decrements in metabolism did not change with protracted alcohol withdrawal and the magnitude of these changes were similar in controls and alcoholics except for a trend towards a blunted response to lorazepam in orbitofrontal cortex in alcoholics during the second evaluation. Abnormalities in orbitofrontal cortex and cingulate gyrus in alcoholics are unlikely to be due to withdrawal since they persist 8 to 11 weeks after detoxification. The fact that there was only a trend of significance for an abnormal response to lorazepam in orbitofrontal cortex indicates that mechanisms other than GABA are involved in the brain metabolic abnormalities observed in alcoholic subjects.

  14. Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism.

    Science.gov (United States)

    Meiser, J; Delcambre, S; Wegner, A; Jäger, C; Ghelfi, J; d'Herouel, A Fouquier; Dong, X; Weindl, D; Stautner, C; Nonnenmacher, Y; Michelucci, A; Popp, O; Giesert, F; Schildknecht, S; Krämer, L; Schneider, J G; Woitalla, D; Wurst, W; Skupin, A; Weisenhorn, D M Vogt; Krüger, R; Leist, M; Hiller, K

    2016-05-01

    The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. The Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans

    DEFF Research Database (Denmark)

    Berg, Ronan M. G.; Plovsing, Ronni R.; Bailey, Damian M.

    2015-01-01

    , noradrenaline administration was associated with a decrease in gain (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P radians; P = 0.58). After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.......81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional...

  16. Empirical Evaluation of Visual Fatigue from Display Alignment Errors Using Cerebral Hemodynamic Responses

    Directory of Open Access Journals (Sweden)

    Hanniebey D. Wiyor

    2013-01-01

    Full Text Available The purpose of this study was to investigate the effect of stereoscopic display alignment errors on visual fatigue and prefrontal cortical tissue hemodynamic responses. We collected hemodynamic data and perceptual ratings of visual fatigue while participants performed visual display tasks on 8 ft × 6 ft NEC LT silver screen with NEC LT 245 DLP projectors. There was statistical significant difference between subjective measures of visual fatigue before air traffic control task (BATC and after air traffic control task (ATC 3, (P<0.05. Statistical significance was observed between left dorsolateral prefrontal cortex oxygenated hemoglobin (l DLPFC-HbO2, left dorsolateral prefrontal cortex deoxygenated hemoglobin (l DLPFC-Hbb, and right dorsolateral prefrontal cortex deoxygenated hemoglobin (r DLPFC-Hbb on stereoscopic alignment errors (P<0.05. Thus, cortical tissue oxygenation requirement in the left hemisphere indicates that the effect of visual fatigue is more pronounced in the left dorsolateral prefrontal cortex.

  17. SirT1 regulates energy metabolism and response to caloric restriction in mice.

    Directory of Open Access Journals (Sweden)

    Gino Boily

    Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

  18. Role of Metabolism by Intestinal Bacteria in Arbutin-Induced Suppression of Lymphoproliferative Response in vitro

    Science.gov (United States)

    Kang, Mi Jeong; Ha, Hyun Woo; Kim, Ghee Hwan; Lee, Sang Kyu; Ahn, Young Tae; Kim, Dong Hyun; Jeong, Hye Gwang; Jeong, Tae Cheon

    2012-01-01

    Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures. PMID:24116295

  19. Cerebral hypoxia

    Science.gov (United States)

    ... before, during, or soon after birth such as cerebral palsy Stroke Very low blood pressure Brain cells are very sensitive to a lack of ... of the eye to light Exams and Tests Cerebral hypoxia can usually be diagnosed based on the person's medical history and a physical exam. Tests are done to ...

  20. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.

    2015-04-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

  1. Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

    Directory of Open Access Journals (Sweden)

    Gitte H Hahn

    Full Text Available BACKGROUND: Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. METHODS: Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy, perfusion (laser-Doppler, oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood, and microvascular heterogeneity (side stream dark field video microscopy. RESULTS: Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01 compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001. These physiologic responses were identical between the three vasopressor-inotropes (p>0.05. Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05. Removal of the scalp tissue did not influence the mismatch (p>0.05. CONCLUSION: We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it

  2. Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets.

    Science.gov (United States)

    Hahn, Gitte H; Hyttel-Sorensen, Simon; Petersen, Sandra M; Pryds, Ole; Greisen, Gorm

    2013-01-01

    Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation. Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy). Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05). We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor

  3. Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

    Directory of Open Access Journals (Sweden)

    Erika Meroni

    2018-02-01

    Full Text Available The ketogenic diet (KD is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB. Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2, significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.

  4. Plant 9-lox oxylipin metabolism in response to arbuscular mycorrhiza.

    Science.gov (United States)

    León Morcillo, Rafael Jorge; Ocampo, Juan A; García Garrido, José M

    2012-12-01

    The establishment of an Arbuscular Mycorrhizal symbiotic interaction (MA) is a successful strategy to substantially promote plant growth, development and fitness. Numerous studies have supported the hypothesis that plant hormones play an important role in the recognition and establishment of symbiosis. Particular attention has been devoted to jasmonic acid (JA) and its derivates, the jasmonates, which are believed to play a major role in AM symbiosis. Jasmonates belong to a diverse class of lipid metabolites known as oxylipins that include other biologically active molecules. Recent transcriptional analyses revealed upregulation of the oxylipin pathway during AM symbiosis in mycorrhizal tomato roots and point a key regulatory feature for oxylipins during AM symbiosis in tomato, particularly these derived from the action of 9-lipoxygenases (9-LOX). In this mini-review we highlight recent progress understanding the function of oxylipins in the establishment of the AM symbiosis and hypothesize that the activation of the 9-LOX pathway might be part of the activation of host defense responses which will then contribute to both, the control of AM fungal spread and the increased resistance to fungal pathogens in mycorrhizal plants.

  5. Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects

    NARCIS (Netherlands)

    Kempen, K.P.G.; Saris, W.H.M.; Senden, J.M.G.; Menheere, P.P.C.A.; Blaak, E.E.; van Baak, M.A.

    1994-01-01

    Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects. Kempen KP, Saris WH, Senden JM, Menheere PP, Blaak EE, van Baak MA. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. This study was intended to investigate the

  6. Transcriptomic Changes in Response to Putrescine Production in Metabolically Engineered Corynebacterium glutamicum

    OpenAIRE

    Li, Zhen; Liu, Jian-Zhong

    2017-01-01

    Putrescine is widely used in industrial production of bioplastics, pharmaceuticals, agrochemicals, and surfactants. Although engineered Corynebacterium glutamicum has been successfully used to produce high levels of putrescine, the overall cellular physiological and metabolic changes caused by overproduction of putrescine remains unclear. To reveal the transcriptional changes that occur in response to putrescine production in an engineered C. glutamicum strain, a comparative transcriptomic an...

  7. Effects of drafting on hydrodynamic and metabolic responses in front crawl swimming

    NARCIS (Netherlands)

    Janssen, M.; Wilson, B.D.; Toussaint, H.M.

    2009-01-01

    Purpose: Effects of drafting on the hydrodynamic and metabolic responses of the drafter behind and at the side of a passive and an active lead swimmer were related to the influence of a lead swimmer on the flow field of the draftee. Methods: Passive drag of the draft swimmer was compared for the

  8. Chromium supplementation enhances the metabolic response of steers to lipopolysaccharide (LPS) challenge

    Science.gov (United States)

    The effect of chromium (Cr; KemTRACE®brandChromiumProprionate 0.04%, Kemin Industries) supplementation on the metabolic response to LPS challenge was examined. Steers (n=20; 235±4 kg body weight (BW)) received a premix that added 0 (Con) or 0.2 mg/kg Cr to the total diet (DM (dry matter) basis) for ...

  9. The Pentose Phosphate Pathway Is a Metabolic Redox Sensor and Regulates Transcription During the Antioxidant Response

    NARCIS (Netherlands)

    Kruger, A.; Gruning, N.M.; Wamelink, M.M.C.; Kerick, M.; Kirpy, A.; Parkhomchuk, D.; Bluemlein, K.; Schweiger, M.R.; Soldatov, A.; Lehrach, H.; Jakobs, C.A.J.M.; Ralser, M.

    2011-01-01

    Aims: A shift in primary carbon metabolism is the fastest response to oxidative stress. Induced within seconds, it precedes transcriptional regulation, and produces reducing equivalents in form of NADPH within the pentose phosphate pathway (PPP). Results: Here, we provide evidence for a regulatory

  10. Yeast supplementation altered the metabolic response to a combined viral-bacterial challenge in feedlot heifers

    Science.gov (United States)

    Two treatments were evaluated in feedlot heifers to determine the effects of feeding a yeast supplement on metabolic responses to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (325 +/- 19.2 kg) were selected and randomly assigned to one of two treatments: 1) Contr...

  11. The effect of environmental temperature on immune response and metabolism of the young chicken

    NARCIS (Netherlands)

    Henken, A.M.

    1982-01-01

    The effect of environmental temperature on immune response and metabolism was studied in young chickens. Immunization was performed by injecting intramuscularly 0.5 ml packed SRBC (sheep red blood cells) in both thighs of 32 days old pullets ( WarrenSSL ). The

  12. Metabolic responses at various intensities relative to critical swimming velocity.

    Science.gov (United States)

    Toubekis, Argyris G; Tokmakidis, Savvas P

    2013-06-01

    To avoid any improper training load, the speed of endurance training needs to be regularly adjusted. Both the lactate threshold (LT) velocity and the velocity corresponding to the maximum lactate steady state (MLSS) are valid and reliable indices of swimming aerobic endurance and commonly used for evaluation and training pace adjustment. Alternatively, critical velocity (CV), defined as the velocity that can be maintained without exhaustion and assessed from swimming performance of various distances, is a valid, reliable, and practical index of swimming endurance, although the selection of the proper distances is a determinant factor. Critical velocity may be 3-6 and 8-11% faster compared with MLSS and LT, respectively. Interval swimming at CV will probably show steady-lactate concentration when the CV has been calculated by distances of 3- to 15-minute duration, and this is more evident in adult swimmers, whereas increasing or decreasing lactate concentration may appear in young and children swimmers. Therefore, appropriate corrections should be made to use CV for training pace adjustment. Findings in young and national level adult swimmers suggest that repetitions of distances of 100-400 m, and velocities corresponding to a CV range of 98-102% may be used for pacing aerobic training, training at the MLSS, and possibly training for improvement of VO2max. Calculation of CV from distances of 200-400, 50-100-200-400, or 100-800 m is an easy and practical method to assess aerobic endurance. This review intends to study the physiological responses and the feasibility of using CV for aerobic endurance evaluation and training pace adjustment, to help coaches to prescribe training sets for different age-group swimmers.

  13. Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects

    OpenAIRE

    Kempen, K.P.G.; Saris, W. H. M.; Senden, J.M.G.; Menheere, P.P.C.A.; Blaak, E.E; Baak, M. A.

    1994-01-01

    Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects. Kempen KP, Saris WH, Senden JM, Menheere PP, Blaak EE, van Baak MA. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. This study was intended to investigate the effects of energy restriction on the acute responses of platelet alpha 2- and lymphocyte beta 2-adrenoceptors to exercise in obese female subjects. Seven obese females were restricted to a low-energ...

  14. Optical metabolic imaging measures early drug response in an allograft murine breast cancer model (Conference Presentation)

    Science.gov (United States)

    Sharick, Joe T.; Cook, Rebecca S.; Skala, Melissa C.

    2017-02-01

    Previous work has shown that cellular-level Optical Metabolic Imaging (OMI) of organoids derived from human breast cancer cell-line xenografts accurately and rapidly predicts in vivo response to therapy. To validate OMI as a predictive measure of treatment response in an immune-competent model, we used the polyomavirus middle-T (PyVmT) transgenic mouse breast cancer model. The PyVmT model includes intra-tumoral heterogeneity and a complex tumor microenvironment that can influence treatment responses. Three-dimensional organoids generated from primary PyVmT tumor tissue were treated with a chemotherapy (paclitaxel) and a PI3K inhibitor (XL147), each alone or in combination. Cellular subpopulations of response were measured using the OMI Index, a composite endpoint of metabolic response comprised of the optical redox ratio (ratio of the fluorescence intensities of metabolic co-enzymes NAD(P)H to FAD) as well as the fluorescence lifetimes of NAD(P)H and FAD. Combination treatment significantly decreased the OMI Index of PyVmT tumor organoids (padaptive immunity. Thus, this method is promising for use in humans to predict long-term treatment responses accurately and rapidly, and could aid in clinical treatment planning.

  15. Larval starvation improves metabolic response to adult starvation in honey bees (Apis mellifera L.).

    Science.gov (United States)

    Wang, Ying; Campbell, Jacob B; Kaftanoglu, Osman; Page, Robert E; Amdam, Gro V; Harrison, Jon F

    2016-04-01

    Environmental changes during development have long-term effects on adult phenotypes in diverse organisms. Some of the effects play important roles in helping organisms adapt to different environments, such as insect polymorphism. Others, especially those resulting from an adverse developmental environment, have a negative effect on adult health and fitness. However, recent studies have shown that those phenotypes influenced by early environmental adversity have adaptive value under certain (anticipatory) conditions that are similar to the developmental environment, though evidence is mostly from morphological and behavioral observations and it is still rare at physiological and molecular levels. In the companion study, we applied a short-term starvation treatment to fifth instar honey bee larvae and measured changes in adult morphology, starvation resistance, hormonal and metabolic physiology and gene expression. Our results suggest that honey bees can adaptively respond to the predicted nutritional stress. In the present study, we further hypothesized that developmental starvation specifically improves the metabolic response of adult bees to starvation instead of globally affecting metabolism under well-fed conditions. Here, we produced adult honey bees that had experienced a short-term larval starvation, then we starved them for 12 h and monitored metabolic rate, blood sugar concentrations and metabolic reserves. We found that the bees that experienced larval starvation were able to shift to other fuels faster and better maintain stable blood sugar levels during starvation. However, developmental nutritional stress did not change metabolic rates or blood sugar levels in adult bees under normal conditions. Overall, our study provides further evidence that early larval starvation specifically improves the metabolic responses to adult starvation in honey bees. © 2016. Published by The Company of Biologists Ltd.

  16. Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer

    Science.gov (United States)

    Dennison, Jennifer B.; Molina, Jennifer R.; Mitra, Shreya; González-Angulo, Ana M.; Balko, Justin M.; Kuba, María G.; Sanders, Melinda E.; Pinto, Joseph A.; Gómez, Henry L.; Arteaga, Carlos L.; Brown, Robert E.; Mills, Gordon B.

    2013-01-01

    Purpose Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer. Methods mRNA microarray data from breast cancer cell lines were used to identify bimodal genes – those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes. Results LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups (odds ratio = 21 for hormone-receptor (HR)-positive/HER2-negative; odds ratio = 10 for triple-negative). Furthermore, high LDHB predicted pathological complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (odds ratio = 4.1, P < .001) and triple-negative (odds ratio = 3.0, P = .003) cancers. For triple-negative tumors without pCR, high LDHB post-treatment also identified proliferative tumors with increased risk of recurrence (hazard ratio = 2.2, P = .006). Conclusions Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50-subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for breast cancer patients receiving neoadjuvant chemotherapy. PMID:23697991

  17. Who is responsible for metabolic screening for mental health clients taking antipsychotic medications?

    Science.gov (United States)

    Ward, Tamara; Wynaden, Dianne; Heslop, Karen

    2018-02-01

    Metabolic syndrome is common in mental health consumer populations, and is linked to cardiovascular disease, stroke and diabetes. Metabolic screening is a way of recognising consumers who are at risk of developing metabolic syndrome but internationally screening rates remain low. A retrospective audit was completed at one Australian public mental health service on the case files of 100 randomly selected consumers to determine nurses level of compliance with metabolic screening policies over a 12 month period. Consumers included in the review were prescribed antipsychotic medications for at least 12 months and had their care in the community coordinated by mental health nurses. Data were entered into an Excel spreadsheet for analysis. Low levels of metabolic screening were identified and these levels decreased over the 12 months under review. No consumers had metabolic screening that recorded all parameters at three monthly intervals over the 12 month period. Only one consumer had every metabolic parameter recorded on the physical health screen tool at baseline assessment. The findings demonstrated that while there is increased awareness of co-morbid physical health issues in this consumer population, the translation of guidelines and policy directives to clinical practice to address this disparity remains low. Improving physical health outcomes is the responsibility of all health professionals, particularly doctors who prescribe and nurses who administer antipsychotic medications regularly to mental health consumers. Moreover, nurses are well placed to demonstrate leadership in reducing the rate of metabolic syndrome through the delivery of holistic care that includes effective screening programs. © 2017 Australian College of Mental Health Nurses Inc.

  18. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  19. Metabolic Responses and Pacing Strategies during Successive Sprint Skiing Time Trials

    DEFF Research Database (Denmark)

    Andersson, Erik; Holmberg, Hans-Christer; Ørtenblad, Niels

    2016-01-01

    PURPOSE: To examine the metabolic responses and pacing strategies during the performance of successive sprint time trials (STTs) in cross-country skiing. METHODS: Ten well-trained male cross-country skiers performed four self-paced 1300-m STTs on a treadmill, each separated by 45 min of recovery...... on the first than second course half. In addition, metabolic rates were substantially higher (~_30%) for uphill than for flat skiing, indicating that pacing was regulated to the terrain. CONCLUSIONS: The fastest STTs were characterized primarily by a greater anaerobic energy production, which also explained 69...

  20. Comparative Proteomics Provides Insights into Metabolic Responses in Rat Liver to Isolated Soy and Meat Proteins.

    Science.gov (United States)

    Song, Shangxin; Hooiveld, Guido J; Zhang, Wei; Li, Mengjie; Zhao, Fan; Zhu, Jing; Xu, Xinglian; Muller, Michael; Li, Chunbao; Zhou, Guanghong

    2016-04-01

    It has been reported that isolated dietary soy and meat proteins have distinct effects on physiology and liver gene expression, but the impact on protein expression responses are unknown. Because these may differ from gene expression responses, we investigated dietary protein-induced changes in liver proteome. Rats were fed for 1 week semisynthetic diets that differed only regarding protein source; casein (reference) was fully replaced by isolated soy, chicken, fish, or pork protein. Changes in liver proteome were measured by iTRAQ labeling and LC-ESI-MS/MS. A robust set totaling 1437 unique proteins was identified and subjected to differential protein analysis and biological interpretation. Compared with casein, all other protein sources reduced the abundance of proteins involved in fatty acid metabolism and Pparα signaling pathway. All dietary proteins, except chicken, increased oxidoreductive transformation reactions but reduced energy and essential amino acid metabolic pathways. Only soy protein increased the metabolism of sulfur-containing and nonessential amino acids. Soy and fish proteins increased translation and mRNA processing, whereas only chicken protein increased TCA cycle but reduced immune responses. These findings were partially in line with previously reported transcriptome results. This study further shows the distinct effects of soy and meat proteins on liver metabolism in rats.

  1. Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia

    Directory of Open Access Journals (Sweden)

    Selena Marini

    2017-08-01

    Full Text Available Patients with liver cirrhosis can develop hyperammonemia and hepatic encephalopathy (HE, accompanied by pronounced daytime sleepiness. Previous studies with healthy volunteers show that experimental increase in blood ammonium levels increases sleepiness and slows the waking electroencephalogram. As ammonium increases a