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Sample records for cerebral metabolic increase

  1. 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......-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...

  2. Complementary acupuncture treatment increases cerebral metabolism in patients with Parkinson's disease.

    Science.gov (United States)

    Huang, Yong; Jiang, Xuemei; Zhuo, Ying; Tang, Anwu; Wik, Gustav

    2009-01-01

    We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.

  3. 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 L

    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...... ammonia concentration and cerebral metabolic rate of blood ammonia (CMRA). We addressed these questions in a paired study design by investigating patients with cirrhosis during and after recovery from an acute episode of HE type C. CMRO(2), CBF, and CMRA were measured by dynamic positron emission...

  4. Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep.

    Science.gov (United States)

    Blood, Arlin B; Hunter, Christian J; Power, Gordon G

    2003-12-15

    Exposure of the fetal sheep to moderate to severe hypoxic stress results in both increased cortical blood flow and decreased metabolic rate. Using intravenous infusion of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist that is permeable to the blood brain barrier, we examine the role of adenosine A1 receptors in mediating cortical blood flow and metabolic responses to moderate hypoxia. The effects of DPCPX blockade are compared to controls as well as animals receiving intravenous 8-(p-sulfophenyl)-theophylline) (8-SPT), a non-selective adenosine receptor antagonist which has been found to be blood brain barrier impermeable. Laser Doppler flow probes, tissue PO2, and thermocouples were implanted in the cerebral cortices of near-term fetal sheep. Catheters were placed in the brachial artery and sagittal sinus vein for collection of samples for blood gas analysis. Three to seven days later responses to a 30-min period of fetal hypoxemia (arterial PO2 10-12 mmHg) were studied with administration of 8-SPT, DPCPX, or vehicle. Cerebral metabolic rate was determined by calculation of both brain heat production and oxygen consumption. In response to hypoxia, control experiments demonstrated a 42 +/- 7 % decrease in cortical heat production and a 35 +/- 10 % reduction in oxygen consumption. In contrast, DPCPX infusion during hypoxia resulted in no significant change in brain heat production or oxygen consumption, suggesting the adenosine A1 receptor is involved in lowering metabolic rate during hypoxia. The decrease in cerebral metabolic rate was not altered by 8-SPT infusion, suggesting that the response is not mediated by adenosine receptors located outside the blood brain barrier. In response to hypoxia, control experiments demonstrated a 35 +/- 7 % increase in cortical blood flow. DPCPX infusion did not change this increase in cortical blood flow, however 8-SPT infusion attenuated increases in flow, indicating that hypoxic

  5. Increased interictal cerebral glucose metabolism in a cortical-subcortical network in drug naive patients with cryptogenic temporal lobe epilepsy.

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    Franceschi, M; Lucignani, G; Del Sole, A; Grana, C; Bressi, S; Minicucci, F; Messa, C; Canevini, M P; Fazio, F

    1995-01-01

    Positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) has been used to assess the pattern of cerebral metabolism in different types of epilepsies. However, PET with [18F]FDG has never been used to evaluate drug naive patients with cryptogenic temporal lobe epilepsy, in whom the mechanism of origin and diffusion of the epileptic discharge may differ from that underlying other epilepsies. In a group of patients with cryptogenic temporal lobe epilepsy, never treated with antiepileptic drugs, evidence has been found of significant interictal glucose hypermetabolism in a bilateral neural network including the temporal lobes, thalami, basal ganglia, and cingular cortices. The metabolism in these areas and frontal lateral cortex enables the correct classification of all patients with temporal lobe epilepsy and controls by discriminant function analysis. Other cortical areas--namely, frontal basal and lateral, temporal mesial, and cerebellar cortices--had bilateral increases of glucose metabolism ranging from 10 to 15% of normal controls, although lacking stringent statistical significance. This metabolic pattern could represent a pathophysiological state of hyperactivity predisposing to epileptic discharge generation or diffusion, or else a network of inhibitory circuits activated to prevent the diffusion of the epileptic discharge. PMID:7561924

  6. 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

    2014-01-01

    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 [18F] 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. PMID:25463973

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

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    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...

  8. Cerebral metabolic adaptation and ketone metabolism after brain injury

    Science.gov (United States)

    Prins, Mayumi L

    2010-01-01

    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the ‘post-weaned/adult’ brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain’s capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation. PMID:17684514

  9. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N

    2010-01-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral...... abolished by glycopyrrolate (P perfusion without affecting the cerebral metabolic rate for oxygen....

  10. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

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    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy.

  11. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    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...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  12. Cerebral vascular control and metabolism in heat stress

    DEFF Research Database (Denmark)

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

    2015-01-01

    implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced...... is in turn the primary mechanism for impaired tolerance to orthostatic challenges. Any reduction in CBF attenuates the brain's convective heat loss, while the hyperthermic-induced increase in metabolic rate increases the cerebral heat gain. This paradoxical uncoupling of CBF to metabolism increases brain...

  13. 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...

  14. Cerebral blood flow and metabolism during sleep.

    Science.gov (United States)

    Madsen, P L; 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 data indicate that global levels of CBF and CMR are about the same during REM sleep as in wakefulness. On the regional level, deep sleep seems to be associated with a uniform decrease in regional CBF and CMR. Investigations concerning regional CBF and CMR during REM sleep are few but data from recent investigations seem to identify site-specific changes in regional CBF and CMR during REM sleep. CBF and CMR are reflections of cerebral synaptic activity and the magnitude of reduction in these variables associated with deep sleep indicates that overall cerebral synaptic activity is reduced to approximately one-half the level associated with wakefulness, while cerebral synaptic activity levels during REM sleep are similar to wakefulness. However, even though the new understanding of CBF and CMR during sleep provides significant and important information of the brain's mode of working during sleep, it does not at its current state identify the physiological processes involved in sleep or the physiological role of sleep.

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

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

    2008-01-01

    .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...

  16. 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.

  17. 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

    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 classi......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......). 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...

  18. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N

    2010-01-01

    ) (P mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate....... Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V(mean) (approximately 16%; P increase in MCA V(mean) during cycling (approximately 15%; P ...Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral...

  19. Cerebral ketone metabolism during development and injury.

    Science.gov (United States)

    Prins, Mayumi L

    2012-07-01

    Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions. Published by Elsevier B.V.

  20. 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 cer

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

    DEFF Research Database (Denmark)

    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......, but increases during cycling exercise. The increase in CMRO(2) is unaffected by beta-adrenergic blockade even though CBF is reduced suggesting that cerebral oxygenation becomes critical and a limited cerebral mitochondrial oxygen tension may induce fatigue. Also, sympathetic activity may drive cerebral non...

  2. Correlation between cerebral oxygen metabolism and cerebral blood flow simultaneously measured before and after acetazolamide administration

    Science.gov (United States)

    Yamaguchi, Hiroichiro; Yamauchi, Hideto; Hazama, Shiro; Hamamoto, Hirotsugu; Inoue, Nobuhiro

    1999-10-01

    The cerebral circulation and metabolism of ten preoperative cardiac surgery patients were assessed. Alterations in regional cerebral blood flow (rCBF), measured by 123I-N- isopropyl-p-iodo-amphetamine single-photon emission computed tomography, and in cerebral oxygen metabolism, simultaneously detected by near-infrared spectroscopy (NIRS) before and after acetazolamide administration, were investigated. The rCBF (ml/min/100 g) increased significantly from 40.21 +/- 7.65 to 56.24 +/- 13.69 (p equals 0.001), and a significant increase in oxyhemoglobin (Oxy-Hb) of 13.9% (p equals 0.0022) and total hemoglobin (Total-Hb) of 5.7% (0.0047) along with a significant decrease in deoxyhemoglobin (Deoxy-Hb) of 8.9% (p equals 0.0414) were observed concomitantly. Thus, the Oxy-Hb/Total- Hb ratio (%Oxy-Hb) rose significantly from 67.26 +/- 9.82% to 72.98 +/- 8.09% (p equals 0.0022). Examination of the relationships between individual parameters showed that the percentage changes in rCBF and Oxy-Hb were significantly correlated (r equals 0.758, p equals 0.011). The percentage changes in rCBF and %Oxy-Hb were also correlated significantly (r equals 0.740, p equals 0.014). In conclusion, this evidence suggested that NIRS is able to detect relative changes in cerebral hemodynamics and reflect luxury perfusion induced by acetazolamide.

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

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    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...

  4. PET measurements of cerebral metabolism corrected for CSF contributions

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    Chawluk, J.; Alavi, A.; Dann, R.; Kushner, M.J.; Hurtig, H.; Zimmerman, R.A.; Reivich, M.

    1984-01-01

    Thirty-three subjects have been studied with PET and anatomic imaging (proton-NMR and/or CT) in order to determine the effect of cerebral atrophy on calculations of metabolic rates. Subgroups of neurologic disease investigated include stroke, brain tumor, epilepsy, psychosis, and dementia. Anatomic images were digitized through a Vidicon camera and analyzed volumetrically. Relative areas for ventricles, sulci, and brain tissue were calculated. Preliminary analysis suggests that ventricular volumes as determined by NMR and CT are similar, while sulcal volumes are larger on NMR scans. Metabolic rates (18F-FDG) were calculated before and after correction for CSF spaces, with initial focus upon dementia and normal aging. Correction for atrophy led to a greater increase (%) in global metabolic rates in demented individuals (18.2 +- 5.3) compared to elderly controls (8.3 +- 3.0,p < .05). A trend towards significantly lower glucose metabolism in demented subjects before CSF correction was not seen following correction for atrophy. These data suggest that volumetric analysis of NMR images may more accurately reflect the degree of cerebral atrophy, since NMR does not suffer from beam hardening artifact due to bone-parenchyma juxtapositions. Furthermore, appropriate correction for CSF spaces should be employed if current resolution PET scanners are to accurately measure residual brain tissue metabolism in various pathological states.

  5. Methylene blue as a cerebral metabolic and hemodynamic enhancer.

    Directory of Open Access Journals (Sweden)

    Ai-Ling Lin

    Full Text Available By restoring mitochondrial function, methylene blue (MB is an effective neuroprotectant in many neurological disorders (e.g., Parkinson's and Alzheimer's diseases. MB has also been proposed as a brain metabolic enhancer because of its action on mitochondrial cytochrome c oxidase. We used in vitro and in vivo approaches to determine how MB affects brain metabolism and hemodynamics. For in vitro, we evaluated the effect of MB on brain mitochondrial function, oxygen consumption, and glucose uptake. For in vivo, we applied neuroimaging and intravenous measurements to determine MB's effect on glucose uptake, cerebral blood flow (CBF, and cerebral metabolic rate of oxygen (CMRO(2 under normoxic and hypoxic conditions in rats. MB significantly increases mitochondrial complex I-III activity in isolated mitochondria and enhances oxygen consumption and glucose uptake in HT-22 cells. Using positron emission tomography and magnetic resonance imaging (MRI, we observed significant increases in brain glucose uptake, CBF, and CMRO(2 under both normoxic and hypoxic conditions. Further, MRI revealed that MB dramatically increased CBF in the hippocampus and in the cingulate, motor, and frontoparietal cortices, areas of the brain affected by Alzheimer's and Parkinson's diseases. Our results suggest that MB can enhance brain metabolism and hemodynamics, and multimetric neuroimaging systems offer a noninvasive, nondestructive way to evaluate treatment efficacy.

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

    DEFF Research Database (Denmark)

    Rasmussen, P; Foged, E. M.; Krogh-Madsen, R

    2010-01-01

    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

  7. The effect of herbs on cerebral energy metabolism in cerebral ischemia-reperfusion mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Vascular dementia is one of the most familiar types of senile dementia. Over the past few years, the research on the damage of cerebral tissues after ischemia has become a focus. The factors and mechanism of cerebral tissue damage after ischemia are very complex. The handicap of energy metabolism is regarded as the beginning factor which leads to the damage of neurons, but its dynamic changes in ischemic area and its role during the process of neuronal damage are not very clear. There are few civil reports on using 31 P nuclear magnetic resonance instrument to explore the changes of cerebral energy metabolism in intravital animals. After exploring the influence of herbs on cerebral energy metabolism in ischemia-reperfusion mice, we came to the conclusion that herbs can improve the cerebral energy metabolism in ischemia-reperfusion mice.

  8. 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).

  9. 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 ...

  10. 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...

  11. 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.

  12. 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...

  13. 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

    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...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation...

  14. 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....

  15. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

    OpenAIRE

    2016-01-01

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography...

  16. 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...... (CMR) of oxygen (O(2)), glucose (glu), and lactate (lac), in patients with ABM and compare the results to those obtained in healthy volunteers. METHODS: We studied 19 patients (17 of whom were sedated) with ABM and eight healthy volunteers (controls). CBF was measured during baseline ventilation...... to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients...

  17. Cerebral blood flow and oxidative metabolism during human endotoxemia

    DEFF Research Database (Denmark)

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

    2002-01-01

    The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines...... 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...

  18. [Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography].

    Science.gov (United States)

    Franck, G; Salmon, E; Poirrier, R; Sadzot, B; Franco, G

    1987-03-01

    Measurements of regional cerebral glucose uptake by the 18F-fluorodeoxyglucose technique (18FDG) and positron emission tomography (PET) along with polygraph recordings were made serially during relaxed wakefulness and different stages of nocturnal sleep in two right-handed normal volunteers. During stage III-IV sleep, values declined diffusely in both hemispheric regions (-31%), thalamus (-33%), cerebellum (-33%) and brain stem (-25%). During paradoxical sleep regional values increased diffusely compared with slow wave sleep. Compared to wakefulness, regional metabolic values seemed to increase but the results were more variable from one volunteer to the other. These preliminary data indicate important regional alterations in cerebral metabolism between sleep states.

  19. Increased cerebral water content in hemodialysis patients.

    Directory of Open Access Journals (Sweden)

    Kathrin Reetz

    Full Text Available Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD on a dialysis-free day and after hemodialysis (2.4±2.2 hours, and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content.

  20. Effects of 1 MAC desflurane on cerebral metabolism, blood flow and carbon dioxide reactivity in humans.

    Science.gov (United States)

    Mielck, F; Stephan, H; Buhre, W; Weyland, A; Sonntag, H

    1998-08-01

    We investigated the cerebral haemodynamic effects of 1 MAC desflurane anaesthesia in nine male patients scheduled for elective coronary bypass grafting. For the measurement of cerebral blood flow (CBF) a modified Kety-Schmidt saturation technique with argon as inert tracer gas was used. Measurements of CBF were made before induction of anaesthesia and 30 min after induction under normocapnic, hypocapnic and hypercapnic conditions in sequence. Changes in mean arterial pressure after induction of anaesthesia and during the course of the study were minimized using norepinephrine infusion. In comparison with the awake state under normocapnic conditions, desflurane reduced mean cerebral metabolic rate of oxygen (CMRO2) by 51% and mean cerebral metabolic rate of glucose (CMRglc) by 35%. Concomitantly, CBF was significantly reduced by 22%; jugular venous oxygen saturation (SjvO2) increased from 58 to 74%. Hypo- and hypercapnia caused a 22% decrease and a 178% increase in CBF, respectively. These findings may be interpreted as the result of two opposing mechanisms: cerebral vasoconstriction induced by a reduction of cerebral metabolism and a direct vasodilator effect of desflurane. CBF alterations under variation of PaCO2 indicate that cerebrovascular carbon dioxide reactivity is not impaired by application of 1 MAC desflurane.

  1. Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors.

    Science.gov (United States)

    Gonzales, Rayna J; Ansar, Saema; Duckles, Sue P; Krause, Diana N

    2007-11-01

    Tissues from males can be regulated by a balance of androgenic and estrogenic effects because of local metabolism of testosterone and expression of relevant steroid hormone receptors. As a critical first step to understanding sex hormone influences in the cerebral circulation of males, we investigated the presence of enzymes that metabolize testosterone to active products and their respective receptors. We found that cerebral blood vessels from male rats express 5alpha-reductase type 2 and aromatase, enzymes responsible for conversion of testosterone into dihydrotestosterone (DHT) and 17beta-estradiol, respectively. Protein levels of these enzymes, however, were not modulated by long-term in vivo hormone treatment. We also showed the presence of receptors for both androgens (AR) and estrogens (ER) from male cerebral vessels. Western blot analysis showed bands corresponding to the full-length AR (110 kDa) and ERalpha (66 kDa). Long-term in vivo treatment of orchiectomized rats with testosterone or DHT, but not estrogen, increased AR levels in cerebral vessels. In contrast, ERalpha protein levels were increased after in vivo treatment with estrogen but not testosterone. Fluorescent immunostaining revealed ERalpha, AR, and 5alpha-reductase type 2 in both the endothelial and smooth muscle layers of cerebral arteries, whereas aromatase staining was solely localized to the endothelium. Thus, cerebral vessels from males are target tissues for both androgens and estrogen. Furthermore, local metabolism of testosterone might balance opposing androgenic and estrogenic influences on cerebrovascular as well as brain function in males.

  2. 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-(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. Significant increased metabolism of [1,2-(13)C]acetate and [U-(13)C]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.

  3. Increased intrathoracic pressure affects cerebral oxygenation following cardiac surgery

    DEFF Research Database (Denmark)

    Pedersen, Lars M; Nielsen, Jonas; Østergaard, Morten

    2012-01-01

    Cerebral oximetry reflects circulatory stability during surgery. We evaluated whether frontal lobe oxygenation is influenced by a transient increase in intrathoracic pressure as induced by a lung recruitment manoeuvre.......Cerebral oximetry reflects circulatory stability during surgery. We evaluated whether frontal lobe oxygenation is influenced by a transient increase in intrathoracic pressure as induced by a lung recruitment manoeuvre....

  4. Cerebral glucose metabolism in patients with spasmodic torticollis

    NARCIS (Netherlands)

    MagyarLehmann, S; Antonini, A; Roelcke, U; Maguire, RP; Missimer, J; Leenders, KL

    1997-01-01

    The pathophysiology of spasmodic torticollis is not clear. Basal ganglia dysfunction has been suggested to underlie this clinical syndrome. We studied resting cerebral glucose metabolism in 10 spasmodic torticollis patients and 10 healthy controls by using positron-emission tomography and [F-18]2-fl

  5. Time-dependent changes in cerebral blood flow after acetazolamide loading into patients with hemodynamic cerebral ischemia. Relationship to cerebral oxygen metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masakazu [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2001-10-01

    The aim of this study was to clarify the relationship between time-dependent changes in cerebral blood flow (CBF) after acetazolamide loading and cerebral oxygen metabolism (CMRO{sub 2}). The subjects consisted of 30 patients with severe stenosis or occlusion of either internal carotid, middle cerebral, or vertebro-basilar artery. Regional CBF was measured at the resting state and 6, 16 and 30 minutes after intravenous administration of 1 gram of acetazolamide using the positron emission tomography in combination with the [{sup 15}O] H{sub 2}O bolus-injection method. Prior to CBF study, regional cerebral oxygen extraction fraction (OEF) was measured using the [{sup 15}O] O{sub 2} inhalation method. Regional CMRO{sub 2} was calculated based on CBF and OEF. According to the time-dependent changes in CBF responses to acetazolamide loading, the CBF responses are classified into good response type, paradoxical response type, and poor response type. Good response type (CBF increase rate more than 20% 6 minutes after acetazolamide loading), paradoxical response type (decrease of CBF 6 minutes after acetazolamide loading) and poor response type (CBF increase rate less than 20% 6 minutes after acetazolamide loading) were identified in 39, 11 and 10 areas, respectively. Brain areas with good response type showed normal OEF and normal CMRO{sub 2}. Brain areas with paradoxical response type showed increased OEF and normal CMRO{sub 2}. Brain areas with poor response type showed normal OEF and decreased CMRO{sub 2}. In view of these findings, the writer concludes that sequential measurement of cerebral blood flow (CBF) after acetazolamide loading enables one to know the regional cerebral oxygen metabolic state in patients with hemodynamic ischemia, and CBF should be measured at an early stage after the administration of acetazolamide to accurately detect misery perfusion. (author)

  6. Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

    Institute of Scientific and Technical Information of China (English)

    Yong Wook Kim; Hyoung Seop Kim; Young-Sil An; Sang Hee Im

    2010-01-01

    Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (Pcorrected <0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (Pcorrected <0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (Puncorrected <0.005).Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  8. 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

    (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG). RESULTS: The global cortical CMRglc decreased with time (p... and parietal cortical areas. There was a statistically significant increase of disability (pEDSS. CONCLUSIONS: Global cortical cerebral metabolism in MS is decreased significantly during a 2...

  9. 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.......05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis...

  10. 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.

  11. Influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Hui Lu; Ning-Ning Cui; Bin-Cheng Wang

    2016-01-01

    Objective:To study the influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease. Methods:A total of 58 patients with ischemic cerebrovascular disease in our hospital from April 2015 to January 2016 were selected as the study object, and 58 patients were randomly divided into two groups, 29 patients in control group were treated with routine treatment, 29 patients in observation group were treated with remote ischemic preconditioning on the basic treatment of control group, then the cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment and at first, third and sixth month after the treatment were respectively detected and compared.Results:The cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment all showed no significant differences (allP>0.05), while the cerebral oxygen metabolism and cerebral blood flow indexes of observation group at first, third and sixth month after the treatment were all significantly better than those before the treatment, and the results were all significantly better than those of control group at the same time too (allP>0.05).Conclusions: The influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease are better, and its application value for the patients with ischemic cerebrovascular disease is higher.

  12. 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).

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

    Science.gov (United States)

    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%Wmax), moderate (50%Wmax), high (75%Wmax) and exhaustive (100%Wmax) workloads. Mean middle cerebral artery blood velocity (MCA Vmean), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide () were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O2), glucose and lactate across the brain. The molar ratio between cerebral uptake of O2 versus carbohydrate (O2–carbohydrate index; O2/[glucose +1/2 lactate]; OCI), the cerebral metabolic rate of O2 (CMRO2) and changes in mitochondrial O2 tension () were calculated. 100%Wmax was ∼33% lower in the older group. Exercise increased MAP and CO in both groups (P exercise intensity (P exercise at ≥75%Wmax. Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals. PMID:23230234

  14. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic

    OpenAIRE

    Powers, William. J.; Videen, Tom O.; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S.

    2011-01-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO2, CMRglc, and other covariates as predictors of resting ...

  15. 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)

  16. 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)

  17. The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

    Science.gov (United States)

    Prins, Mayumi L; Matsumoto, Joyce H

    2014-12-01

    The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. Does the risk of cerebral palsy increase or decrease with increasing gestational age?

    Directory of Open Access Journals (Sweden)

    Murphy-Kaulbeck Lynn

    2003-12-01

    Full Text Available Abstract Background It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. Methods We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. Results Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at Conclusions The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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...... 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 ...-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...

  1. How Energy Metabolism Supports Cerebral Function: Insights from (13)C Magnetic Resonance Studies In vivo.

    Science.gov (United States)

    Sonnay, Sarah; Gruetter, Rolf; Duarte, João M N

    2017-01-01

    Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS), several groups have worked on assessing cerebral metabolism in vivo. In this context, (1)H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. (1)H-[(13)C] MRS, i.e., indirect detection of signals from (13)C-coupled (1)H, together with infusion of (13)C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of (13)C isotopomers), the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct (13)C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

  2. How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

    Directory of Open Access Journals (Sweden)

    Sarah Sonnay

    2017-05-01

    Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

  3. 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.

  4. Increase of cerebral blood flow at high altitude

    DEFF Research Database (Denmark)

    Lassen, N A

    1992-01-01

    CBF increases with acute hypoxia despite the opposing vasoconstrictor effects of the drop in pCO2 caused by hyperventilation. Maintaining normocapnia by adding CO2 the hypoxic CBF responsiveness about doubles. As we have shown recently by this test, the hypoxic CBF response is not blunted but rat...... vasodilatation cannot explain the usual (mild) form of AMS. But it may well be involved in the pathogenesis of the rare but severe cerebral form of AMS, as prolonged increased capillary pressure in vasodilated areas could lead to vasogenic cerebral edema....

  5. Is there any association between cerebral vasoconstriction/vasodilatation and microdialysis Lactate to Pyruvate ratio increase?

    Science.gov (United States)

    Asgari, Shadnaz; Vespa, Paul; Hu, Xiao

    2013-08-01

    Although abnormally high Lactate/Pyruvate ratio (LPR) could indicate cerebral ischemia for brain injury patients, there is a debate on what is primary factor responsible for LPR increase. A data analysis experiment is taken to test whether any association between cerebral vasodilatation/vasoconstriction and LPR increase exists. We studied 4,316 microdialysis data samples collected in an average interval of 1.3 h from 30 severe traumatic brain injury (TBI) patients. The LPR increase episodes were automatically identified using a moving time-window of 5 samples. A novel pulse morphological template matching (PMTM) algorithm was applied to the intracranial pressure (ICP) data of the corresponding patients to assess the occurrence of cerebral vasodilatation and vasoconstriction during the identified LPR increase episodes. Several analyses were performed to evaluate the association between cerebral vasoconstriction/vasodilatation and LPR increase. Results revealed that although more than half of the LPR increase episodes are not associated with any detected cerebral vasoconstriction/vasodilatation, when a vaso-change happens in association of LPR increase, it is more likely that this vaso-change is in the form of vasoconstriction rather than vasodilatation. Also for few subjects with dominant number of vasoconstriction episodes, a causality relationship between vasoconstriction and LPR increase were observed (vasoconstriction precedes LPR increase). Using continuous intracranial pressure monitoring and our pulse morphological template matching (PMTM) algorithm could be potentially helpful in teasing out whether culprit cerebral vascular changes precede metabolic crisis for traumatic brain injury patients and hence guiding the management of this condition.

  6. Local cerebral glucose metabolism during controlled hypoxemia in rats.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1979-05-11

    2-Deoxy-[14C]glucose metabolism was examined in brains of hypoxic, normotensive rats by autoradiography, which revealed alternating cortical columns of high and low metabolism. Activity in white matter was increased severalfold over that in adjacent gray matter. The columns were anatomically related to penetrating cortical arteries with areas between arteries demonstrating higher rates of metabolism. The results suggest the presence of interarterial tissue oxygen gradients that influence regional glucose metabolism. The relatively greater sensitivity of white matter metabolism to hypoxia may lead to an understanding of white matter damage in postanoxic leukoencephalopathy.

  7. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Levy, D E; Duffy, T E

    1982-05-01

    Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.

  8. 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

  9. 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

  10. Mental stress and cognitive performance do not increase overall level of cerebral O2 uptake in humans

    DEFF Research Database (Denmark)

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

    1992-01-01

    We measured cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral lactate output during rest, during the execution of mental arithmetic, and during mental stress induced by physical and psychological annoyance. Measurements were performed in healthy volunteers by use...... stress induced a slight but highly significant (P less than 0.002) 6% reduction in global CMRO2. This finding is in contrast to results from earlier investigations and contradicts the generally accepted notion of an association between mental arousal and a diffuse upregulation of cerebral synaptic...... activity. During mental arithmetic and mental stress, cerebral lactate output increased by 207 and 344%, respectively, but because of large individual variations in the measured responses, the elevations reached statistical significance only during mental arithmetic....

  11. Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

    Science.gov (United States)

    Sokoloff, Max D; Plegue, Melissa A; Chervin, Ronald D; Barks, John D E; Shellhaas, Renée A

    2015-07-01

    Near-infrared spectroscopy (NIRS) measures oxygen metabolism and is increasingly used for monitoring critically ill neonates. The implications of NIRS-recorded data in this population are poorly understood. We evaluated NIRS monitoring for neonates with seizures. In neonates monitored with video-electroencephalography, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 s. Mean rSO2 was extracted for 1-h blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of three times the duration of the seizure before and after the ictal pattern, as well as during the seizure. Linear mixed models were developed to assess the impact of phenobarbital administration and of seizures on rSO2 and fractional tissue oxygen extraction. For 20 neonates (estimated gestational age: 39.6 ± 1.5 wk), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (P = 0.005), and fractional tissue oxygen extraction declined (P = 0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and postictal phases (baseline 81.2 vs. ictal 77.7 vs. postictal 79.4; P = 0.004). Fractional tissue oxygen extraction was highest during seizures (P = 0.002). Cerebral oxygen metabolism decreases after phenobarbital administration and increases during seizures. These small, but clear, changes in cerebral oxygen metabolism merit assessment for potential clinical impact.

  12. Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

    Institute of Scientific and Technical Information of China (English)

    Li-Hua Zou; Jin-Ping Liu; Hao Zhang; Shu-Bin Wu; Bing-Yang Ji

    2016-01-01

    Background:Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA).However,brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology.Methods:To clarify the metabolomics profiling of ASCP,12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group,n =6) and without (DHCA [D] group,n =6) ASCP according to the random number table.ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery.Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass.The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry.Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites,and then Student's t-test was applied to test for statistical significance between the two groups.Results:Metabolic profiling of brain was distinctive significantly between the two groups (Q2y =0.88 for partial least squares-DA model).In comparing to group D,62 definable metabolites were varied significantly after ASCP,which were mainly related to amino acid metabolism,carbohydrate metabolism,and lipid metabolism.Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway,subdued anaerobic metabolism,and oxidative stress.In addition,L-kynurenine (P =0.0019),5-methoxyindole-3-acetic acid (P =0.0499),and 5-hydroxyindole-3-acetic acid (P =0.0495) in tryptophan metabolism pathways were decreased,and citrulline (P =0.0158) in urea cycle was increased in group DA comparing to group D.Conclusions:The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP

  13. 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).

  14. 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.

  15. EFFECT OF ELECTRO0-SCALP ACUPUNCTURE ON GLUCOSE METABOLISM OF THE CEREBRAL REGIONS INVOLVING MENTAL ACTIVITY IN HEAL THY PEOPLE

    Institute of Scientific and Technical Information of China (English)

    HUANG Yong(黄泳); Win Moe Htut; LI Dong-jiang(李东江); TANG An-wu(唐安戊); LI Qiu-shi(李求实)

    2004-01-01

    Objective: To observe the effect of electro-scalp acupuncture on glucose metabolism of cerebral regions involving mental activity in healthy people. Methods: A total of 6 cases of volunteer healthy subjects (3 males and 3 females) ranging in age from 22 to 36 years were subjected to this study. Changes of cerebral glucose metabolism before and after electro-scalp acupuncture were observed by using positron emission tomography (PET) and semi-quantifying analysis method. Electro-scalp acupuncture stimulation (50 Hz, 2 mA) of Middle Line of Vertex (Dingzhongxian,顶中线,MS5), Middle Line of Forehead (Ezhongxian, 额中线,MS1) and bilateral Lateral Line 1 of Forehead (Epangyixian,额旁一线,MS2) was administered for 30 minutes. Then cerebral regions of interest (ROIs) were chosen and their average glucose metabolism levels (radioactivity of 18 fluorine deoxyglucose ) were analyzed. Results:After administration of electro-scalp acupuncture, the glucose metabolism levels in bilateral frontal lobes and bilateral caudate nuclei, left cingulate gyrus and right cerebellum increased significantly in comparison with those of pre-stimulation (P<0.05). Conclusion:Electro-scalp acupuncture of MS1, MS2 and MS5 can increase the glucose metabolism of certain cerebral regions involving in mental activity in healthy subjects.

  16. 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.

  17. 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.

  18. Influence of rotating magnetic field on cerebral infarction volume, cerebral edema and free radicals metabolism after cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Liu; Zhiqiang Zhang; Lixin Zhang

    2006-01-01

    BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually.OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction,cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University.MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute.METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa's method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2

  19. 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

  20. PET imaging of cerebral perfusion and oxygen metabolism in stroke

    Energy Technology Data Exchange (ETDEWEB)

    Pointon, O.; Yasaka, M.; Berlangieri, S.U.; Newton, M.R.; Thomas, D.L.; Chan, C.G.; Egan, G.F.; Tochon-Danguy, H.J.; O``Keefe, G.; Donnan, G.A.; McKay, W.J. [Austin Hospital, Melbourne, VIC (Australia). Centre for PET and Depts of Nuclear Medicine and Neurology

    1998-03-01

    Full text: Stroke remains a devastating clinical event with few therapeutic options. In patients with acute stroke, we studied the cerebral perfusion and metabolic patterns with {sup 15}O-CO{sub 2} or H{sub 2}O and {sup 15}O-O{sub 2} positron emission tomography and correlated these findings to the clinical background. Forty three patients underwent 45 studies 0-23 days post-stroke (mean 7 days). Fifteen patients showed luxury perfusion (Group A), 10 had matched low perfusion and metabolism (B) and 3 showed mixed pattern including an area of misery perfusion (C). Seventeen showed no relevant abnormality (D) and there were no examples of isolated misery perfusion. Twelve of the 15 in Group A had either haemorrhagic transformation on CT, re-opening on angiography, or a cardioembolic mechanism. In contrast only 5/10 in Group B, 0/3 in Group C and 2/17 in Group D had these features. Although 7/10 in group B had moderate or large size infarcts on CT the incidence of haemorrhagic transformation was low (2/10) and significant carotid stenoses were more common in those studied (5/8) compared with the other groups. Misery perfusion was not seen beyond five days. Thus, luxury perfusion seems to be related to a cardio-embolic mechanism or reperfusion. Matched low perfusion and metabolism was associated with a low rate of haemorrhagic transformation despite a high incidence of moderate to large size infarcts. Misery perfusion is an early phenomenon in the evolution of ischaemic stroke.

  1. EXPLORING THE MECHANISM OF ACUPUNCTURE IN THE TREATMENT OF STROKE FROM CHANGES OF GLUCOSE METABOLISM IN THE CEREBRAL MOTOR CENTER

    Institute of Scientific and Technical Information of China (English)

    石现; 左芳; 关玲

    2004-01-01

    Objective:To observe the effect of acupuncture on cerebral glucose metabolism in stroke patients.Methods:Changes of cerebral glucose metabolism before and after acupuncture stimulation were observed in six cases of stroke patients by using positron emission tomography (PET) scanner. Electroacupuncture (EA,4 Hz, continuous waves and duration of 20 min) was applied to Baihui (百会GV 20) and right Qubin (曲鬓GB 7). 18 Fluorine deoxyglucose (18FDG), a developer (radioactive form of glucose) for showing the levels of the brain functional activity was given to the patients intravenously. SPM software was used to deal with the data of each pixel point by unilateral t-test (Ts: P=0.05), then, the regions showing increase/decrease of the glucose metabolism were obtained.Results:After acupuncture stimulation, significant increase of glucose metabolism was found to be in the first somatic motor cortical region (MI), supplementary motor area (SMA), premotor area (PMC), and the superior parietal lobule (LPs) on the healthy side of the brain; while the decrease of glucose metabolism found in MI, PMC and LPs on the focus side. In addition to the cerebral regions related to the motor function, changes of glucose metabolism were also found in the parietal lobule and basal ganglion area, central parietal gyrus, superior parietal gyrus, putamen, cerebellum, etc..Conclusion:Acupuncture of Qubin (GB 7) and Baihui (GV 20) can activate motor-related cerebral structures in the bilateral cerebral hemisphere and induce excitement reaction of the potentially correlative motor area so as to compensate or assist the injured motor area to play a role in improving motor function in stroke patients.

  2. New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

    Science.gov (United States)

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    2016-06-30

    The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

  3. Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation.

    Science.gov (United States)

    Marowsky, Anne; Haenel, Karen; Bockamp, Ernesto; Heck, Rosario; Rutishauser, Sibylle; Mule, Nandkishor; Kindler, Diana; Rudin, Markus; Arand, Michael

    2016-12-01

    Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. We hypothesized that this evolutionary avoidance is due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. To test this, we generated mEH E404D mice and assessed them for detoxification capacity and vascular dynamics. In liver microsomes from these mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide was four times faster compared to WT liver microsomes, confirming accelerated detoxification. mEH E404D animals also showed faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios were found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism. Because EETs are strong vasodilators in cerebral vasculature, hemodynamics were assessed in mEH E404D and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV0 levels were similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide were reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. These results demonstrate a critical role for mEH E404D in vasodynamics and suggest that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant.

  4. 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)

  5. Simple exercises that significantly increase cerebral blood flow and cerebral oxygenation

    CERN Document Server

    Gersten, Alexander; Raz, Amir; Fried, Robert

    2011-01-01

    We tested the hypothesis that simple exercises may significantly increase cerebral blood flow (CBF) and/or cerebral oxygenation. Eighteen subjects ranging in age from nineteen to thirty nine participated in a four-stage study during which measurements of end tidal CO_2 (EtCO2 - by capnometer) and local brain oxygenation (by near-infrared spectroscopy (NIRS) sensor) were taken. The four stages were 1) baseline, 2) breathing exercises, 3) solving an arithmetic problem, and 4) biofeedback. During the breathing exercises there was a significant increase in EtCO2 indicating a significant increase in global CBF. The increase in global CBF was estimated on the basis of a theoretical model. During the arithmetic and biofeedback tasks there was a significant increase in the local (Fp1) oxygenation, but it varied between the different participants. The results may lead to new clinical applications of CBF and brain oxygenation monitoring and behavioral control. We foresee future more detailed investigations in the contr...

  6. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome.

    Science.gov (United States)

    Harrell, John W; Schrage, William G

    2014-01-15

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor.

  7. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine Miyama Hospital (Japan)); Doi, C. (Tohoku Univ. School of Literature (Japan). Dept. of Psychology); Yamaguchi, T.; Sasaki, H. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine); Matsui, H.; Yamada, K. (Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Kinomura, S. (Miyama Hospital (Japan) Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Itoh, M. (Tohoku Univ. School of Medicine (Japan). Cyclotron Radioisotope Center)

    1991-08-01

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the {sup 18}-F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.).

  8. Changes in cerebral oxidative metabolism during neonatal seizures following hypoxic ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Subhabrata Mitra

    2016-08-01

    Full Text Available Seizures are common following hypoxic ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain, however the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO] and hemodynamics during recurrent neonatal seizures following hypoxic ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude integrated electro-encephalogram (aEEG. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean EEG voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism.

  9. 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

  10. EFFECT OF ACUPUNCTURE STIMULATION AT SANYINJIAO (SP 6) ON CEREBRAL GLUCOSE METABOLISM IN DYSMENORRHEA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    GONG Ping; ZHANG Ming-min; JIANG Li-ming; WU Zhi-jian; WANG Wei; HUANG Guang-ying

    2006-01-01

    Objective: To study the central mechanism of acupuncture stimulation of Sanyinjiao ( 三阴交 SP6) in relieving dysmenorrhea. Methods: A total of 6 dysmenorrhea volunteer patients were subjected into this study. On the first positron emission tomography (PET) scan examination, they were assigned to pseudoacupuncture group by using the acupuncture needle just to prick the skin of Sanyinjiao (SP 6); while on the second PET scans, they were assigned to acupuncture group by inserting the needle into the same acupoint.18F fluorodeoxyglucose (18F-FDG) PET of the whole brain was performed during pseudo-acupuncture and real acupuncture of Sanyinjiao (SP 6). The acquired PET data were analyzed by using statistical parametric mapping (SPM) software to determine changes of glucose metabolism in different cerebral regions. The patient's pain intensity was rated by using 0- 10 numerical pain intensity scale. Results: After pseudo-acupuncture stimulation of Sanyinjiao (SP 6), no significant changes were found in the pain intensity ( P >0.05), while after real-acupuncture stimulation, the pain intensity declined significantly (P < 0.01 ). Following acupuncture of the right Sanyinjiao (SP 6), multiple cerebral regions involving pain were activated (increase of glucose metabolism), including ipsilateral lenticular nucleus (globus pallidus, putamen), ipsilateral cerebellum and insular lobe, bilateral dorsal thalamus, ipsilateral paracentral lobule, bilateral amygdaloid bodies, contralateral substantia nigra of the midbrain, bilateral second somatosensory (S Ⅱ ) areas, ispsilateral hippocampal gyrus, frontal part of the ipsilateral cingulated gyrus, and bilateral mammary bodies of the hypothalamus. In addition, fewer regions of the cerebral cortex responded with decrease of the glucose metabolism after real acupuncture.

  11. 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...... and the internal jugular bulb. RESULTS: A net cerebral ammonia uptake was only found in patients with FHF (1.62 +/- 0.79 micromol x 100 g(-1) x min(-1)). The cerebral glutamine efflux was higher in patients with FHF than in the healthy subjects and cirrhotics, -6.11 +/- 5.19 vs. -1.93 +/- 1.17 and -1.50 +/- 0...

  12. 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

    capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain......, 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....... Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations Udgivelsesdato: 2008/1...

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

    DEFF Research Database (Denmark)

    Seifert, Thomas; Secher, Niels H

    2011-01-01

    -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......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...

  14. Enhanced metabolic capacity of the frontal cerebral cortex after Pavlovian conditioning.

    Science.gov (United States)

    Bruchey, A K; Gonzalez-Lima, F

    2008-03-18

    While Pavlovian conditioning alters stimulus-evoked metabolic activity in the cerebral cortex, less is known about the effects of Pavlovian conditioning on neuronal metabolic capacity. Pavlovian conditioning may increase prefrontal cortical metabolic capacity, as suggested by evidence of changes in cortical synaptic strengths, and evidence for a shift in memory initially processed in subcortical regions to more distributed prefrontal cortical circuits. Quantitative cytochrome oxidase histochemistry was used to measure cumulative changes in brain metabolic capacity associated with both cued and contextual Pavlovian conditioning in rats. The cued conditioned group received tone-foot-shock pairings to elicit a conditioned freezing response to the tone conditioned stimulus, while the contextually conditioned group received pseudorandom tone-foot-shock pairings in an excitatory context. Untrained control group was handled daily, but did not receive any tone presentations or foot shocks. The cued conditioned group had higher cytochrome oxidase activity in the infralimbic and anterior cingulate cortex, and lower cytochrome oxidase activity in dorsal hippocampus than the other two groups. A significant increase in cytochrome oxidase activity was found in anterior cortical areas (medial, dorsal and lateral frontal cortex; agranular insular cortex; lateral and medial orbital cortex and prelimbic cortex) in both conditioned groups, as compared with the untrained control group. In addition, no differences in cytochrome oxidase activity in the somatosensory regions and the amygdala were detected among all groups. The findings indicate that cued and contextual Pavlovian conditioning induces sustained increases in frontal cortical neuronal metabolic demand resulting in regional enhancement in the metabolic capacity of anterior cortical regions. Enhanced metabolic capacity of these anterior cortical areas after Pavlovian conditioning suggests that the frontal cortex may play a

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

    Science.gov (United States)

    Schlünzen, L; Juul, N; Hansen, K V; Gjedde, A; Cold, G E

    2010-05-01

    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. Eight volunteers underwent two dynamic 18F-fluorodeoxyglucose positron emission tomography (PET) scans. One scan assessed conscious-baseline metabolism and the other scan assessed metabolism during 1 minimum alveolar concentration (MAC) sevoflurane anaesthesia. Cardiovascular and respiratory parameters were monitored and bispectral index responses were registered. Statistical parametric maps and conventional regions of interest analysis were used to determine rGMR differences. All subjects were unconsciousness at 1.0 MAC sevoflurane. Cardiovascular and respiratory parameters were constant over time. In the awake state, rGMR ranged from 0.24 to 0.35 mumol/g/min in the selected regions. Compared with the conscious state, total GMR decreased 56% in sevoflurane anaesthesia. In white and grey matter, GMR was averaged 42% and 58% of normal, respectively. Sevoflurane reduced the absolute rGMR in all selected areas by 48-71% of the baseline (P< or = 0.01), with the most significant reductions in the lingual gyrus (71%), occipital lobe in general (68%) and thalamus (63%). No increases in rGMR were observed. Sevoflurane caused a global whole-brain metabolic reduction of GMR in all regions of the human brain, with the most marked metabolic suppression in the lingual gyrus, thalamus and occipital lobe.

  16. 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.

  17. Lactate storm marks cerebral metabolism following brain trauma.

    Science.gov (United States)

    Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

    2014-07-18

    Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure.

  18. 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...... associated with light anesthesia. During REM sleep (dream sleep) CMRO2 was practically the same as in the awake state. Changes in CBF paralleled changes in CMRO2 during both deep and REM sleep....

  19. 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...

  20. Positron emission tomography in cerebrovascular disease: The relationship between regional cerebral blood flow, blood volume and oxygen metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Herold, S.

    1985-03-01

    Positron emission tomography in cerebrovascular disease has demonstrated the importance of the relationship between regional cerebral blood flow and the cerebral metabolic activity. In acute stroke it has been found that within the first hours after the onset of symptoms cerebral blood flow in the affected area is more depressed than cerebral oxygen utilisation. This relative preservation of oxygen utilisation results from an increase in the oxygen extraction ratio far above its normal value. However, the oxygen extraction fraction subsequently falls in the following days indicating the transition from a situation of possibly reversible ischaemia to irreversible infarction. In patients with carotid occlusive disease an increase in the oxygen extraction ratio has been observed only in very few cases. It has been shown, however, that at an earlier stage the relationship between CBF and CBV (as CBF/CBV-ratio) provides a sensitive measure of diminished perfusion pressure which could be helpful for the selection of patients for EC-IC bypass surgery. In patients with sickle cell anaemia it has been found that oxygen delivery to the brain is maintained by an increase in cerebral blood flow, whereas the oxygen extraction ratio is not increased despite the presence of a low oxygen affinity haemoglobin. Preliminary observations in classical migraine suggest an ischaemic situation during the attack.

  1. 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.

  2. 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...

  3. Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

    Science.gov (United States)

    Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

    2013-03-01

    We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

  4. 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 magnet...... & Metabolism advance online publication, 28 March 2012; doi:10.1038/jcbfm.2012.34....

  5. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

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

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  6. Brain metabolic markers reflect susceptibility status in cytokine gene knockout mice with murine cerebral malaria.

    Science.gov (United States)

    Parekh, Sapan B; Bubb, William A; Hunt, Nicholas H; Rae, Caroline

    2006-11-01

    Treatment of cerebral malaria, a complication of the world's most significant parasitic disease, remains problematic due to lack of understanding of its pathogenesis. Metabolic changes, along with cytokine expression alterations and blood cell sequestration in the brain, have previously been reported during severe disease in human infection and mouse models leading to the "cytopathic hypoxia" and "sequestration" theories of pathogenesis. Here, to determine the robustness of the metabolic changes and their relationship to disease development, we investigated changes in cerebral metabolic markers in a mouse model of cerebral malaria (CM) in wildtype (C57BL/6) and cytokine knockout (TNF(-/-), IFNgamma(-/-) and LTalpha(-/-)) mice using multinuclear magnetic resonance spectroscopy. Mice susceptible to CM (wildtype, TNF(-/-)) showed decreased cerebral glucose use, decreased Krebs cycle metabolism and decreased high-energy phosphates. Conversely, mice resistant to CM (IFNgamma(-/-), LTalpha(-/-)) showed little sign of these effects, despite identical levels of parasitemia. Previously reported changes in lactate were shown to be strain dependent. Elevated glutamine and decreased phosphorylation potential emerged as robust metabolic markers of susceptibility, further implicating the trytophan/NAD(+) pathway in disease development. Thus these metabolic changes are firmly linked both to the immune system response to malaria and to the occurrence of pathogenic changes in experimental CM.

  7. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine) (and others)

    1989-11-01

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author).

  8. Metabolic pattern of the acute phase of subarachnoid hemorrhage in a novel porcine model: studies with cerebral microdialysis with high temporal resolution.

    Directory of Open Access Journals (Sweden)

    Christoffer Nyberg

    Full Text Available BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed. OBJECTIVE: To study early cerebral energy changes in an animal model. METHODS: Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate. RESULTS: In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia. CONCLUSION: The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.

  9. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  10. DDT increases hepatic testosterone metabolism in rats.

    Science.gov (United States)

    Sierra-Santoyo, Adolfo; Hernández, Manuel; Albores, Arnulfo; Cebrián, Mariano E

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-14C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2alpha-hydroxytestosterone (OHT), and 16alpha-OHT but higher 6beta-OHT whereas treated females produced less 7alpha-OHT and AD but higher 6beta-OHT and 6alpha-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6beta-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6alpha-/15alpha-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6alpha-/16alpha-OHT and 6-dehydrotestosterone/16alpha-OHT ratios followed a similar tendency, with the ratio 6alpha-/16alpha-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats.

  11. 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.

  12. 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

    . At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery...

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

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Østergaard, Karen;

    2012-01-01

    AIM: Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2...

  14. Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic.

    Science.gov (United States)

    Powers, William J; Videen, Tom O; Markham, Joanne; Walter, Vonn; Perlmutter, Joel S

    2011-05-01

    Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO(2), CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO(2) was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO(2): arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO(2) and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.

  15. 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.

  16. 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

    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...

  17. Program for PET image alignment: Effects on calculated differences in cerebral metabolic rates for glucose

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-12-01

    A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states.

  18. 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.

  19. 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

    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...... 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...... with control at the end of exercise (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P

  20. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Science.gov (United States)

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  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. Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy

    NARCIS (Netherlands)

    Schaafsma, A.; de Jong, B M; Bams, J.L.; Haaxma-Reiche, H; Pruim, J; Zijlstra, J G

    2003-01-01

    Positron emission tomography (PET) was used for the study of regional cerebral perfusion and metabolism in eight patients with severe post-hypoxic encephalopathy, caused by cardiac arrest and resulting in a coma lasting for at least 24 h. Using this method, we aimed to identify regional vulnerabilit

  3. Functional MRI of CO2 induced increase in cerebral perfusion

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B

    1994-01-01

    The sensitivity of MR gradient echo imaging towards CO2 induced changes in cerebral blood flow was investigated in 10 normal subjects. The subjects were inhaling 5% and 7% CO2 and the experiments were carried out at 1.5 T (n = 6) and 2.0 T (n = 5), allowing a comparison of field strengths. Additi...

  4. Increased cerebral blood flow in preeclampsia with magnetic resonance imaging

    NARCIS (Netherlands)

    Zeeman, GG; Hatab, MR; Twickler, DM

    2004-01-01

    Objective: The purpose of this study was to compare third trimester and nonpregnant cerebral blood flow of women with preeclampsia to normotensive control subjects with the use of magnetic resonance imaging techniques. Study design: Nine normotensive pregnant women and 12 untreated women with preecl

  5. Functional MRI of CO2 induced increase in cerebral perfusion

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B;

    1994-01-01

    The sensitivity of MR gradient echo imaging towards CO2 induced changes in cerebral blood flow was investigated in 10 normal subjects. The subjects were inhaling 5% and 7% CO2 and the experiments were carried out at 1.5 T (n = 6) and 2.0 T (n = 5), allowing a comparison of field strengths...

  6. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism

    National Research Council Canada - National Science Library

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-01-01

    .... We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells...

  7. Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G

    2009-01-01

    This study examined whether hypoxia causes free radical-mediated disruption of the blood-brain barrier (BBB) and impaired cerebral oxidative metabolism and whether this has any bearing on neurological symptoms ascribed to acute mountain sickness (AMS). Ten men provided internal jugular vein...

  8. 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.

  9. Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased Calpain and caspase activity and can be reduced by erythropoietin treatment

    DEFF Research Database (Denmark)

    Hempel, Casper; Hoyer, Nils; Kildemoes, Anna

    2014-01-01

    increased levels of VEGF in brain and plasma and decreased plasma levels of soluble VEGF receptor 2. EPO treatment normalized VEGF receptor 2 levels and reduced brain VEGF levels. Hypoxia-inducible factor (HIF)-1α was significantly upregulated whereas cerebral HIF-2α and EPO levels remained unchanged....... Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of α-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HIF-1α, which in the brain were reduced to normal in EPO-treated mice. Also...

  10. 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...... were obtained by cerebral arteriovenous differences. In both SAH rats and controls, hyperventilation decreased CBF in proportion to the decrement in PaCO2 without affecting either CMRO2, CMRglc, or CMRlac. In groups C and D, CBF decreased by 20%-35%, but CMRs were maintained by a compensatory increase...

  11. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    Science.gov (United States)

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle.

  12. 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

    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......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...

  13. 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.

  14. Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Maigaard, Katrine; Wörtwein, Gitta

    2013-01-01

    and Tnf). The metabolism cage housing in itself did not significantly influence a range of biological stress markers. In the restraint stress group, there was a sustained 2.5 fold increase in 24h corticosterone excretion from day 2 after stress initiation. However, neither whole-body nor cerebral measures...

  15. 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

  16. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    Science.gov (United States)

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  17. 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

  18. 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

  19. Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes.

    Science.gov (United States)

    Cho, Sang Soo; Aminian, Kelly; Li, Crystal; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2017-01-01

    Fatigue is a common and disabling non-motor symptom in Parkinson's disease associated with a feeling of overwhelming lack of energy. The aim of this study was to identify the neural substrates that may contribute to the development of fatigue in Parkinson's disease. Twenty-three Parkinson's disease patients meeting UK Brain Bank criteria for the diagnosis of idiopathic Parkinson's disease were recruited and completed the 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)-PET scan. The metabolic activities of Parkinson's disease patients with fatigue were compared to those without fatigue using statistical parametric mapping analysis. The Parkinson's disease group exhibiting higher level of fatigue showed anti-correlated metabolic changes in cortical regions associated with the salience (i.e., right insular region) and default (i.e., bilateral posterior cingulate cortex) networks. The metabolic abnormalities detected in these brain regions displayed a significant correlation with level of fatigue and were associated with a disruption of the functional correlations with different cortical areas. These observations suggest that fatigue in Parkinson's disease may be the expression of metabolic abnormalities and impaired functional interactions between brain regions linked to the salience network and other neural networks. Hum Brain Mapp 38:283-292, 2017. © 2016 Wiley Periodicals, Inc.

  20. Typical Cerebral Metabolic Patterns in Neurodegenerative Brain Diseases

    NARCIS (Netherlands)

    Teune, Laura K.; Bartels, Anna L.; de Jong, Bauke M.; Willemsen, Antoon T. M.; Eshuis, Silvia A.; de Vries, Jeroen J.; van Oostrom, Joost C. H.; Leenders, Klaus L.

    2010-01-01

    The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [F-18]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting t

  1. 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

    Alterations in brain energy metabolism have been suggested to be of fundamental importance for the development of Alzheimer's disease (AD). However, specific changes in brain energetics in the early stages of AD are poorly known. The aim of this study was to investigate cerebral energy metabolism...... 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...... by mass spectrometry. The ATP synthesis rate of isolated whole-brain mitochondria was assessed by an on-line luciferin-luciferase assay. Significantly increased (13)C labeling of intracellular lactate and alanine and decreased tricarboxylic acid (TCA) cycle activity were observed from cerebral cortical...

  2. Effects of Metformin on the Cerebral Metabolic Changes in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Yung-Cheng Huang

    2014-01-01

    Full Text Available Metformin, a widely used antidiabetic drug, has numerous effects on human metabolism. Based on emerging cellular, animal, and epidemiological studies, we hypothesized that metformin leads to cerebral metabolic changes in diabetic patients. To explore metabolism-influenced foci of brain, we used 2-deoxy-2-[18F]fluoro-D-glucose (FDG positron emission tomography for type 2 diabetic patients taking metformin (MET, n=18, withdrawing from metformin (wdMET, n=13, and not taking metformin (noMET, n=9. Compared with the noMET group, statistical parametric mapping showed that the MET group had clusters with significantly higher metabolism in right temporal, right frontal, and left occipital lobe white matter and lower metabolism in the left parahippocampal gyrus, left fusiform gyrus, and ventromedial prefrontal cortex. In volume of interest (VOI- based group comparisons, the normalized FDG uptake values of both hypermetabolic and hypometabolic clusters were significantly different between groups. The VOI-based correlation analysis across the MET and wdMET groups showed a significant negative correlation between normalized FDG uptake values of hypermetabolic clusters and metformin withdrawal durations and a positive but nonsignificant correlation in the turn of hypometabolic clusters. Conclusively, metformin affects cerebral metabolism in some white matter and semantic memory related sites in patients with type 2 diabetes.

  3. Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

    Science.gov (United States)

    Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

    2012-05-01

    Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

  4. Effect of sevoflurane and propofol on cerebral oxygen metabolism in cardiopulmonary bypass and postoperative neurological function injury

    Institute of Scientific and Technical Information of China (English)

    Zhu Zhu; Wei-Wei Li

    2016-01-01

    Objective:To study the effect of sevoflurane and propofol on cerebral oxygen metabolism in cardiopulmonary bypass (CPB) and postoperative neurological function injury.Methods:A total of 48 cases of patients who received mitral valve replacement under CPB in our hospital were selected and randomly divided into sevoflurane group (S group) and propofol group (P group) who received sevoflurane-based intravenous inhalational anesthesia and propofol-based total intravenous anesthesia respectively, cerebral oxygen metabolism indexes were determined before CPB started (T0), when nasopharyngeal temperature fell to a constant low temperature (T1), when CPB ended (T2) and 1 h after CPB ended (T3) respectively during operation, and serum neurological function, cardiac function and liver function injury molecules were determined after operation.Results: Intraoperative SjvO2, AVDO2, O2ER and rSO2 were not significantly different between two groups, SjvO2 at T1 significantly increased, AVDO2 and O2ER significantly decreased and rSO2 didn’t change significantly, SjvO2 at T2 significantly decreased, AVDO2 and O2ER significantly increased and rSO2 didn’t change significantly; postoperative serum NSE, S100β, Aβ, Glu, Asp and Gly levels of S group were significantly lower than those of P group, and CK-MB, LDH, cTnI, ALT and AST levels were not significantly different from those of P group.Conclusion:Both sevoflurane and propofol can maintain the balance of cerebral oxygen metabolism in mitral valve replacement under CPB and protect the cardiac function and liver function, but sevoflurane has more ideal protective effect on postoperative neurological function.

  5. APP metabolism regulates tau proteostasis in human cerebral cortex neurons

    OpenAIRE

    Steven Moore; Evans, Lewis D.B.; Therese Andersson; Erik Portelius; James Smith; Tatyana B. Dias; Nathalie Saurat; Amelia McGlade; Peter Kirwan; Kaj Blennow; John Hardy; Henrik Zetterberg; Frederick J. Livesey

    2015-01-01

    This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S2211124715003599. 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, a...

  6. Recombinant human erythropoietin increases cerebral cortical width index and neurogenesis following ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Zhongmin Wen; Peiji Wang

    2012-01-01

    The cerebral cortical expansion index refers to the ratio between left and right cortex width and is recognized as an indicator for cortical hyperplasia. Cerebral ischemia was established in CB-17 mice in the present study, and the mice were subsequently treated with recombinant human erythropoietin via subcutaneous injection. Results demonstrated that cerebral cortical width index significantly increased. Immunofluorescence detection showed that the number of nuclear antigen antibody/5-bromodeoxyuridine-positive cells at the infarction edge significantly increased. Correlation analysis revealed a negative correlation between neurological scores and cortical width indices in rats following ischemic stroke. These experimental findings suggested that recombinant human erythropoietin promoted cerebral cortical hyperplasia, increased cortical neurogenesis, and enhanced functional recovery following ischemic stroke.

  7. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    OpenAIRE

    Balestri, P; Lucignani, G; Fois, A.; Magliani, L; Calistri, L; Grana, C.; Di Bartolo, R M; Perani, D; Fazio, F.

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This fi...

  8. Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome.

    Science.gov (United States)

    Yamada, Yoshiji; Kato, Kimihiko; Oguri, Mitsutoshi; Yoshida, Tetsuro; Yokoi, Kiyoshi; Watanabe, Sachiro; Metoki, Norifumi; Yoshida, Hidemi; Satoh, Kei; Ichihara, Sahoko; Aoyagi, Yukitoshi; Yasunaga, Akitomo; Park, Hyuntae; Tanaka, Masashi; Nozawa, Yoshinori

    2008-06-01

    Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (PA (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

  9. Influence of antihypertensive therapy on cerebral perfusion in patients with metabolic syndrome: relationship with cognitive function and 24-h arterial blood pressure monitoring.

    Science.gov (United States)

    Efimova, Nataliya Y; Chernov, Vladimir I; Efimova, Irina Y; Lishmanov, Yuri B

    2015-08-01

    To investigate the regional cerebral blood flow, cognitive function, and parameters of 24-h arterial blood pressure monitoring in patients with metabolic syndrome before and after combination antihypertensive therapy. The study involved 54 patients with metabolic syndrome (MetS) investigated by brain single-photon emission computed tomography, 24-h blood pressure monitoring (ABPM), and comprehensive neuropsychological testing before and after 24 weeks of combination antihypertensive therapy. Patients with metabolic syndrome had significantly poorer regional cerebral blood flow compared with control group: by 7% (P = 0.003) in right anterior parietal cortex, by 6% (P = 0.028) in left anterior parietal cortex, by 8% (P = 0.007) in right superior frontal lobe, and by 10% (P = 0.00002) and 7% (P = 0.006) in right and left temporal brain regions, correspondingly. The results of neuropsychological testing showed 11% decrease in mentation (P = 0.002), and 19% (P = 0.011) and 20% (P = 0.009) decrease in immediate verbal and visual memory in patients with MetS as compared with control group. Relationships between the indices of ABPM, cerebral perfusion, and cognitive function were found. Data showed an improvement of regional cerebral blood flow, ABPM parameters, and indicators of cognitive functions after 6 months of antihypertensive therapy in patients with MetS. The study showed the presence of diffuse disturbances in cerebral perfusion is associated with cognitive disorders in patients with metabolic syndrome. Combination antihypertensive treatment exerts beneficial effects on the 24-h blood pressure profile, increases cerebral blood flow, and improves cognitive function in patients with MetS. © 2015 John Wiley & Sons Ltd.

  10. 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.

  11. Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased Calpain and caspase activity and can be reduced by erythropoietin treatment

    DEFF Research Database (Denmark)

    Hempel, Casper; Hoyer, Nils; Kildemoes, Anna;

    2014-01-01

    . Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of α-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HIF-1α, which in the brain were reduced to normal in EPO-treated mice. Also...... caspase and calpain activity was reduced markedly in EPO-treated mice....

  12. Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain

    Directory of Open Access Journals (Sweden)

    Shoichi Takikita

    2015-09-01

    Full Text Available Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A. In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes. This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.

  13. Increased apoptosis and hypomyelination in cerebral white matter of macular mutant mouse brain.

    Science.gov (United States)

    Takikita, Shoichi; Takano, Tomoyuki; Narita, Tsutomu; Maruo, Yoshihiro

    2015-09-01

    Hypomyelination in developing brain is often accompanied by congenital metabolic disorders. Menkes kinky hair disease is an X-linked neurodegenerative disease of impaired copper transport, resulting from a mutation of the Menkes disease gene, a transmembrane copper-transporting p-type ATPase gene (ATP7A). In a macular mutant mouse model, the murine ortholog of Menkes gene (mottled gene) is mutated, and widespread neurodegeneration and subsequent death are observed. Although some biochemical analysis of myelin protein in macular mouse has been reported, detailed histological study of myelination in this mouse model is currently lacking. Since myelin abnormality is one of the neuropathologic findings of human Menkes disease, in this study early myelination in macular mouse brain was evaluated by immunohistochemistry. Two-week-old macular mice and normal littermates were perfused with 4% paraformaldehyde. Immunohistochemical staining of paraffin embedded and vibratome sections was performed using antibodies against either CNPase, cleaved caspase-3 or O4 (marker of immature oligodendrocytes). This staining showed that cerebral myelination in macular mouse was generally hypoplastic and that hypomyelination was remarkable in internal capsule, corpus callosum, and cingulate cortex. In addition, an increased number of cleaved caspase-3 positive cells were observed in corpus callosum and internal capsule. Copper deficiency induced by low copper diet has been reported to induce oligodendrocyte dysfunction and leads to hypomyelination in this mouse model. Taken together, hypomyelination observed in this study in a mouse model of Menkes disease is assumed to be induced by increased apoptosis of immature oligodendrocytes in developing cerebrum, through deficient intracellular copper metabolism.

  14. 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.

  15. Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

    Science.gov (United States)

    Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

    2010-02-01

    Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

  16. 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

    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...... (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG). RESULTS: The global cortical CMRglc decreased with time (p...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...

  17. Flux analysis in plant metabolic networks: increasing throughput and coverage.

    Science.gov (United States)

    Junker, Björn H

    2014-04-01

    Quantitative information about metabolic networks has been mainly obtained at the level of metabolite contents, transcript abundance, and enzyme activities. However, the active process of metabolism is represented by the flow of matter through the pathways. These metabolic fluxes can be predicted by Flux Balance Analysis or determined experimentally by (13)C-Metabolic Flux Analysis. These relatively complicated and time-consuming methods have recently seen significant improvements at the level of coverage and throughput. Metabolic models have developed from single cell models into whole-organism dynamic models. Advances in lab automation and data handling have significantly increased the throughput of flux measurements. This review summarizes advances to increase coverage and throughput of metabolic flux analysis in plants.

  18. 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

    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......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.......d.) and the arterial-jugular venous (a-v) difference from -0.02 +/- 0.03 mm at rest to 1.0 +/- 0.5 mm (P increased from 0.7 +/- 0.3 to 0.9 +/- 0.1 mm (P

  19. 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

  20. 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.)

  1. 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.

  2. Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis

    DEFF Research Database (Denmark)

    Wang, Qian; Paulson, O B; Lassen, N A

    1993-01-01

    Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused...

  3. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Institute of Scientific and Technical Information of China (English)

    Yi Zhang; Chun-Sheng Li; Cai-Jun Wu; Jun Yang; Chen-Chen Hang

    2015-01-01

    Background:Morbidity and mortality after resuscitation largely depend on the recovery of brain function.Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death.Up to now,most studies have focused on VFCA.However,results from the two models have been largely variable.So,it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.Methods:Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups:18 for VFCA group,ACA group,respectively,and other 8 for sham-operated group (SHAM).VFCA was induced by programmed electric stimulation,andACA was induced by endotracheal tube clamping.After 8 min without treatment,standard cardiopulmonary resuscitation (CPR) was initiated.Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation,cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography.Levels of serum markers of brain injury,neuron specific enolase (NSE),and S100β were quantified with an enzyme-linked immunosorbent assay.Results:Compared with VFCA group,fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs.94.4%,P < 0.01) and survived 24-h after resuscitation (38.9% vs.77.8%,P < 0.01) with worse neurological outcome (NDS:244.3 ± 15.3 vs.168.8 ± 9.71,P < 0.01).The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs.4.5 ± 1.1 min,P < 0.01).Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01).Higher serum biomarkers of brain damage (NSE,S100β) were found inACA than VFCA after resuscitation (P < 0.01).Conclusions:Compared with VFCA,ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.

  4. Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2015-01-01

    Full Text Available Background: Morbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA and asphyxial cardiac arrest (ACA are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models. Methods: Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM. VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR was initiated. Following neurological deficit scores (NDS were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax was measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE, and S100β were quantified with an enzyme-linked immunosorbent assay. Results: Compared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01 and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01 with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01. The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01. Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01. Higher serum biomarkers of brain damage (NSE, S100β were found in ACA than VFCA after resuscitation (P < 0.01. Conclusions: Compared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse

  5. Reduced blood flow response to acetazolamide reflects pre-existing vasodilation and decreased oxygen metabolism in major cerebral arterial occlusive disease

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Hiroshi; Okazawa, Hidehiko; Kishibe, Yoshihiko; Sugimoto, Kanji; Takahashi, Masaaki [Research Institute, Shiga Medical Center, 5-4-30 Moriyama, Moriyama-city, Shiga 524-8524 (Japan)

    2002-10-01

    A decrease in the cerebral blood flow (CBF) response to acetazolamide may indicate an increase in cerebral blood volume (CBV) caused by reduced perfusion pressure in patients with major cerebral artery steno-occlusive lesions. However, a decrease in cerebral metabolic rate of oxygen (CMRO{sub 2}) caused by ischemic changes may also decrease the CBF response to acetazolamide by decreasing the production of carbon dioxide. The purpose of this study was to determine whether the values of CBV and CMRO{sub 2} are independent predictors of the CBF response to acetazolamide in major cerebral arterial occlusive disease. We used positron emission tomography to study 30 patients with major cerebral artery steno-occlusive lesions. The CBF response to acetazolamide was assessed by measuring baseline CBF and CBF 10 min after an intravenous injection of 1 g of acetazolamide. Multivariate analysis was used to test the independent predictive value of the CBV and CMRO{sub 2} at baseline with respect to the percent change in CBF during acetazolamide administration. Both increased CBV and decreased CMRO{sub 2} were significant and independent predictors of the reduced CBF response to acetazolamide. CBV accounted for 25% of the variance in the absolute change in CBF during acetazolamide administration and 42% of the variance in the percent change in CBF, whereas CMRO{sub 2} accounted for 19% and 4% of the variance, respectively. In patients with major cerebral arterial occlusive disease, a decrease in CMRO{sub 2} may contribute to the reduced CBF response to acetazolamide, although an increase in CBV appears to be the major contributing factor. (orig.)

  6. Effect of increases in cardiac contractility on cerebral blood flow in humans.

    Science.gov (United States)

    Ogoh, Shigehiko; Moralez, Gilbert; Washio, Takuro; Sarma, Satyam; Hieda, Michinari; Romero, Steven A; Cramer, Matthew N; Shibasaki, Manabu; Crandall, Craig G

    2017-09-15

    The effect of acute increases in cardiac contractility on cerebral blood flow (CBF) remains unknown. We hypothesized that the external carotid artery (ECA) downstream vasculature modifies the direct influence of acute increases in heart rate and cardiac function on CBF regulation. Twelve healthy subjects received two infusions of dobutamine (first a low dose; 5 μg/kg/min and then a high dose; 15 μg/kg/min) for 12 min each. Cardiac output, blood flow through the internal carotid artery (ICA) and ECA and echocardiographic measurements were performed during dobutamine infusions. Despite increases in cardiac contractility, cardiac output and arterial pressure with dobutamine, ICA blood flow and conductance slightly decreased from resting baseline during both low and high dose infusions. In contrast, ECA blood flow and conductance increased appreciably during both low and high dose infusions. Greater ECA vascular conductance and corresponding increases in blood flow may protect over-perfusion of intracranial cerebral arteries during enhanced cardiac contractility and associated increases in cardiac output and perfusion pressure. Importantly, these findings suggest that the acute increase of blood perfusion due to dobutamine administration does not cause cerebral over-perfusion or an associated risk of cerebral vascular damage. Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology.

  7. 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.

  8. Functional MRI of CO2 induced increase in cerebral perfusion

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B

    1994-01-01

    . Additional experiments were carried out using a higher spatial resolution. The largest signal increases were noted in areas corresponding to larger vessels, but significant changes were also conspicuous in deeper cortical and central grey matter. The changes appeared linearly related to the arterial CO2...... tension, within the range of PaCO2 studied. In white matter, the changes were not statistically significant....

  9. 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.

  10. Stress-related changes in cerebral catecholamine and indoleamine metabolism: lack of effect of adrenalectomy and corticosterone.

    Science.gov (United States)

    Dunn, A J

    1988-08-01

    The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.

  11. Increased Cerebral Blood Flow Velocity in Children with Mild Sleep-Disordered Breathing

    Science.gov (United States)

    Hill, Catherine M.; Hogan, Alexandra M.; Onugha, Nwanneka; Harrison, Dawn; Cooper, Sara; McGrigor, Victoria J.; Datta, Avijit; Kirkham, Fenella J.

    2007-01-01

    Objective Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits. Design Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended

  12. Glycopyrrolate does not influence the visual or motor-induced increase in regional cerebral perfusion

    DEFF Research Database (Denmark)

    Rokamp, Kim Z; Olesen, Niels D; Larsson, Henrik B W

    2014-01-01

    Acetylcholine may contribute to the increase in regional cerebral blood flow (rCBF) during cerebral activation since glycopyrrolate, a potent inhibitor of acetylcholine, abolishes the exercise-induced increase in middle cerebral artery mean flow velocity. We tested the hypothesis that cholinergic...... vasodilatation is important for the increase in rCBF during cerebral activation. The subjects were 11 young healthy males at an age of 24 ± 3 years (mean ± SD). We used arterial spin labeling and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to evaluate rCBF with and without...... intravenous glycopyrrolate during a handgrip motor task and visual stimulation. Glycopyrrolate increased heart rate from 56 ± 9 to 114 ± 14 beats/min (mean ± SD; p mean arterial pressure from 86 ± 8 to 92 ± 12 mmHg, and cardiac output from 5.6 ± 1.4 to 8.0 ± 1.7 l/min. Glycopyrrolate had, however...

  13. 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.

  14. 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)

  15. In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy

    Science.gov (United States)

    Deng, Zilin; Wang, Zhen; Yang, Xiaoquan; Luo, Qingming; Gong, Hui

    2012-08-01

    Stroke is a devastating disease. The changes in cerebral hemodynamics and oxygen metabolism associated with stroke play an important role in pathophysiology study. But the changes were difficult to describe with a single imaging modality. Here the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen saturation (SO2) were yielded with laser speckle imaging (LSI) and photoacoustic microscopy (PAM) during and after 3-h acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF). The results indicate that all the hemodynamics except CBV had rapid declines within 40-min occlusion of middle cerebral artery (MCAO). CBV in arteries and veins first increased to the maximum value of 112.42±36.69% and 130.58±31.01% by 15 min MCAO; then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic. When ischemia lasted for 3 h, CBF in arteries, veins decreased to 17±14.65%, 24.52±20.66%, respectively, CBV dropped to 62±18.56% and 59±18.48%. And the absolute SO2 decreased by 40.52±22.42% and 54.24±11.77%. After 180-min MCAO, the changes in hemodynamics and oxygen metabolism were also quantified. The study suggested that combining LSI and PAM provides an attractive approach for stroke detection in small animal studies.

  16. RATIONALE FOR PREVENTION OF CARDIO-CEREBRAL COMPLICATIONS IN THE METABOLIC SYNDROME BASED ON MATHEMATICAL FORECASTING TECHNIQUES

    Directory of Open Access Journals (Sweden)

    S. V. Chernavskii

    2011-01-01

    Full Text Available Objective — to study prevention of cardio-cerebral complications of metabolic syndrome on the basis of mathematical methods of forecasting.Subjects and methods. A discriminant analysis of clinical and instrumental data of patients with MS.Results of this study allow the early (prenosological stages of the metabolic syndrome using the linear discriminant equations to predict thedevelopment of myocardial infarction up to 89.3 %, stroke — up to 87.8 %.Conclusion. The diagnostic and treatment algorithms developed based on the stratification of cardiovascular risk index, allow us to give sound recommendations for targeted prevention of cardio-cerebral complications.

  17. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

    Science.gov (United States)

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-07-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging.

  18. Influence of apolipoprotein E and its receptors on cerebral amyloid precursor protein metabolism following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shuai; SUN Xiao-chuan

    2012-01-01

    Traumatic brain injury (TBI) is the leading cause of mortality and disability among young individuals in our society,and globally the incidence of TBI is rising sharply.Mounting evidence has indicated that apolipoprotein E (apoE:protein; APOE:gene) genotype influences the outcome after TBI.The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition,disruption of lipid distribution,dysfunction of mitochondrial energy production,oxidative stress and increases intracellular calcium in response to injury.This paper reviews the current state of knowledge regarding the influence of apoE and its receptors on cerebral amyloid betaprotein precursor metabolism following TBI.

  19. Restricted Arm Swing Affects Gait Stability and Increased Walking Speed Alters Trunk Movements in Children with Cerebral Palsy

    Science.gov (United States)

    Delabastita, Tijs; Desloovere, Kaat; Meyns, Pieter

    2016-01-01

    Observational research suggests that in children with cerebral palsy, the altered arm swing is linked to instability during walking. Therefore, the current study investigates whether children with cerebral palsy use their arms more than typically developing children, to enhance gait stability. Evidence also suggests an influence of walking speed on gait stability. Moreover, previous research highlighted a link between walking speed and arm swing. Hence, the experiment aimed to explore differences between typically developing children and children with cerebral palsy taking into account the combined influence of restricting arm swing and increasing walking speed on gait stability. Spatiotemporal gait characteristics, trunk movement parameters and margins of stability were obtained using three dimensional gait analysis to assess gait stability of 26 children with cerebral palsy and 24 typically developing children. Four walking conditions were evaluated: (i) free arm swing and preferred walking speed; (ii) restricted arm swing and preferred walking speed; (iii) free arm swing and high walking speed; and (iv) restricted arm swing and high walking speed. Double support time and trunk acceleration variability increased more when arm swing was restricted in children with bilateral cerebral palsy compared to typically developing children and children with unilateral cerebral palsy. Trunk sway velocity increased more when walking speed was increased in children with unilateral cerebral palsy compared to children with bilateral cerebral palsy and typically developing children and in children with bilateral cerebral palsy compared to typically developing children. Trunk sway velocity increased more when both arm swing was restricted and walking speed was increased in children with bilateral cerebral palsy compared to typically developing children. It is proposed that facilitating arm swing during gait rehabilitation can improve gait stability and decrease trunk movements in

  20. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    Science.gov (United States)

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. ©2014 American Association for Cancer Research.

  1. Pattern of cerebral glucose metabolism on F-18 FDG brain PET during vomiting and symptom free periods in cyclic vomiting syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Lee, Dong Soo; Kang, Eun Joo; Seo, Jeong Kee; Yeo, Jeong Seok; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2001-06-01

    Cyclic Vomiting Syndrome (CVS) is characterized by recurrent, periodic, self-limiting vomiting. However, its pathogenesis is not yet established. We investigated the changes of the cerebral glucose metabolism using F-18 FDG during the vomiting attack and symptom free period in two children with CVS. FDG PET study showed the markedly increased metabolism in both temporal lobes and also in the medulla and cerebellum during the vomiting period. Also, FDG PET showed the decreased metabolism in the parieto-occipital and occipital areas during the in vomiting period. The area with decreased metabolism seemed to be related with the region showing abnormalities in EEG and perfusion SPECT studies. We expect that what we observed would be a helpful finding in clarifying the pathogenesis of the CVS.

  2. Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    陈志刚; 卢亦成; 朱诚; 张光霁; 丁学华; 江基尧

    2003-01-01

    Objective: To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI).Methods: An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed.Results: After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P0.05) was observed.Conclusions: Ganglioside GM1 does have obvious neuroprotective effect on early TBI.

  3. 20-Hydroxyeicosatetraenoic Acid Inhibition by HET0016 Offers Neuroprotection, Decreases Edema, and Increases Cortical Cerebral Blood Flow in a Pediatric Asphyxial Cardiac Arrest Model in Rats.

    Science.gov (United States)

    Shaik, Jafar Sadik B; Poloyac, Samuel M; Kochanek, Patrick M; Alexander, Henry; Tudorascu, Dana L; Clark, Robert Sb; Manole, Mioara D

    2015-11-01

    Vasoconstrictive and vasodilatory eicosanoids generated after cardiac arrest (CA) may contribute to cerebral vasomotor disturbances and neurodegeneration. We evaluated the balance of vasodilator/vasoconstrictor eicosanoids produced by cytochrome P450 (CYP) metabolism, and determined their role on cortical perfusion, functional outcome, and neurodegeneration after pediatric asphyxial CA. Cardiac arrest of 9 and 12 minutes was induced in 16- to 18-day-old rats. At 5 and 120 minutes after CA, we quantified the concentration of CYP eicosanoids in the cortex and subcortical areas. In separate rats, we inhibited 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis after CA and assessed cortical cerebral blood flow (CBF), neurologic deficit score, neurodegeneration, and edema. After 9 minutes of CA, vasodilator eicosanoids markedly increased versus sham. Conversely, after 12 minutes of CA, vasoconstrictor eicosanoid 20-HETE increased versus sham, without compensatory increases in vasodilator eicosanoids. Inhibition of 20-HETE synthesis after 12 minutes of CA decreased cortical 20-HETE levels, increased CBF, reduced neurologic deficits at 3 hours, and reduced neurodegeneration and edema at 48 hours versus vehicle-treated rats. In conclusion, cerebral vasoconstrictor eicosanoids increased after a pediatric CA of 12 minutes. Inhibition of 20-HETE synthesis improved cortical perfusion and short-term neurologic outcome. These results suggest that alterations in CYP eicosanoids have a role in cerebral hypoperfusion and neurodegeneration after CA and may represent important therapeutic targets.

  4. 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...... 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...... nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus...

  5. Role of Aquaporin-4 in Cerebral Edema and Stroke

    OpenAIRE

    Zador, Zsolt; Stiver, Shirley; Wang, Vincent; MANLEY, GEOFFREY T.

    2009-01-01

    Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechan...

  6. Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vemuri, Goutham; Eiteman, M.A; McEwen, J.E

    2007-01-01

    Respiratory metabolism plays an important role in energy production in the form of ATP in all aerobically growing cells. However, a limitation in respiratory capacity results in overflow metabolism, leading to the formation of byproducts, a phenomenon known as ‘‘overflow metabolism’’ or ‘‘the...... Crabtree effect.’’ The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely...... by overexpression of a water-forming NADH oxidase reduced aerobic glycerol formation. The metabolic response to elevated alternative oxidase occurred predominantly in the mitochondria, whereas NADH oxidase affected genes that catalyze cytosolic reactions. Moreover, NADH oxidase restored the deficiency of cytosolic...

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  12. [Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique].

    Science.gov (United States)

    Bassani, Mariana Almada; Caldas, Jamil Pedro Siqueira; Netto, Abimael Aranha; Marba, Sérgio Tadeu Martins

    2016-06-01

    To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. This is an intervention study, which included 40 preterm infants (≤34 weeks) aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5minutes. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50), the end diastolic flow velocity (p=0.17), the mean flow velocity (p=0.07), the resistance index (p=0.41) and the pulsatility index (p=0.67) over time. The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  13. Cerebral blood flow assessment of preterm infants during respiratory therapy with the expiratory flow increase technique

    Directory of Open Access Journals (Sweden)

    Mariana Almada Bassani

    2016-06-01

    Full Text Available Abstract Objective: To assess the impact of respiratory therapy with the expiratory flow increase technique on cerebral hemodynamics of premature newborns. Methods: This is an intervention study, which included 40 preterm infants (≤34 weeks aged 8-15 days of life, clinically stable in ambient air or oxygen catheter use. Children with heart defects, diagnosis of brain lesion and/or those using vasoactive drugs were excluded. Ultrasonographic assessments with transcranial Doppler flowmetry were performed before, during and after the increase in expiratory flow session, which lasted 5min. Cerebral blood flow velocity and resistance and pulsatility indices in the pericallosal artery were assessed. Results: Respiratory physical therapy did not significantly alter flow velocity at the systolic peak (p=0.50, the end diastolic flow velocity (p=0.17, the mean flow velocity (p=0.07, the resistance index (p=0.41 and the pulsatility index (p=0.67 over time. Conclusions: The expiratory flow increase technique did not affect cerebral blood flow in clinically-stable preterm infants.

  14. Fat burners: nutrition supplements that increase fat metabolism.

    Science.gov (United States)

    Jeukendrup, A E; Randell, R

    2011-10-01

    The term 'fat burner' is used to describe nutrition supplements that are claimed to acutely increase fat metabolism or energy expenditure, impair fat absorption, increase weight loss, increase fat oxidation during exercise, or somehow cause long-term adaptations that promote fat metabolism. Often, these supplements contain a number of ingredients, each with its own proposed mechanism of action and it is often claimed that the combination of these substances will have additive effects. The list of supplements that are claimed to increase or improve fat metabolism is long; the most popular supplements include caffeine, carnitine, green tea, conjugated linoleic acid, forskolin, chromium, kelp and fucoxanthin. In this review the evidence for some of these supplements is briefly summarized. Based on the available literature, caffeine and green tea have data to back up its fat metabolism-enhancing properties. For many other supplements, although some show some promise, evidence is lacking. The list of supplements is industry-driven and is likely to grow at a rate that is not matched by a similar increase in scientific underpinning.

  15. Voxel-based statistical analysis of cerebral glucose metabolism in the rat cortical deafness model by 3D reconstruction of brain from autoradiographic images

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Park, Kwang Suk [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea); Seoul National University College of Medicine, Department of Biomedical Engineering, Seoul (Korea); Ahn, Soon-Hyun; Oh, Seung Ha; Kim, Chong Sun; Chung, June-Key; Lee, Myung Chul [Seoul National University College of Medicine, Department of Otolaryngology, Head and Neck Surgery, Seoul (Korea); Lee, Dong Soo; Jeong, Jae Min [Seoul National University College of Medicine, Department of Nuclear Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul (Korea)

    2005-06-01

    any other area, and no area showed a significant increase in metabolism in the deaf rats with the same threshold, demonstrating the high localization accuracy and specificity of the method developed in this study. This study established new procedures for the 3D reconstruction and voxel-based analysis of autoradiographic data which will be useful for examining the cerebral glucose metabolism in a rat cortical deafness model. (orig.)

  16. Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation

    Science.gov (United States)

    Carneiro, Lionel; Geller, Sarah; Hébert, Audrey; Repond, Cendrine; Fioramonti, Xavier; Leloup, Corinne; Pellerin, Luc

    2016-01-01

    Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis. PMID:27708432

  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. Nerve transfer helps repair brachial plexus injury by increasing cerebral cortical plasticity

    Institute of Scientific and Technical Information of China (English)

    Guixin Sun; Zuopei Wu; Xinhong Wang; Xiaoxiao Tan; Yudong Gu

    2014-01-01

    In the treatment of brachial plexus injury, nerves that are functionally less important are trans-ferred onto the distal ends of damaged crucial nerves to help recover neuromuscular function in the target region. For example, intercostal nerves are transferred onto axillary nerves, and accessory nerves are transferred onto suprascapular nerves, the phrenic nerve is transferred onto the musculocutaneous nerves, and the contralateral C7 nerve is transferred onto the median or radial nerves. Nerve transfer has become a major method for reconstructing the brachial plexus after avulsion injury. Many experiments have shown that nerve transfers for treatment of brachi-al plexus injury can help reconstruct cerebral cortical function and increase cortical plasticity. In this review article, we summarize the recent progress in the use of diverse nerve transfer methods for the repair of brachial plexus injury, and we discuss the impact of nerve transfer on cerebral cortical plasticity after brachial plexus injury.

  19. Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse.

    Science.gov (United States)

    Yong, T; Zheng, M Q; Linthicum, D S

    1997-10-01

    Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.

  20. Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction.

    Science.gov (United States)

    Jensen, Jens H; Falangola, Maria F; Hu, Caixia; Tabesh, Ali; Rapalino, Otto; Lo, Calvin; Helpern, Joseph A

    2011-06-01

    By application of the MRI method of diffusional kurtosis imaging, a substantially increased diffusional kurtosis was observed within the cerebral ischemic lesions of three stroke subjects, 13-26 h following the onset of symptoms. This increase is interpreted as probably reflecting a higher degree of diffusional heterogeneity in the lesions when compared with normal-appearing contralateral tissue. In addition, for two of the subjects with white matter infarcts, the increase had a strong fiber tract orientational dependence. It is proposed that this effect is consistent with a large drop in the intra-axonal diffusivity, possibly related to either axonal varicosities or alterations associated with the endoplasmic reticulum.

  1. Focal increase of cerebral blood flow during stereognostic testing in man

    DEFF Research Database (Denmark)

    Roland, E; Larsen, B

    1976-01-01

    An attempt was made to study the regional cerebral blood flow (rCBF) pattern during stereognostic discrimination in man. The rCBF was measured in 18 subjects who had no major neurological defects. The clearance from the hemisphere of xenon 133 injected (133Xe) into the carotid artery was measured...... with a 254-channel dynamic gamma camera. During stereognostic discrimination with hand, mouth, or foot, the rCBF increased focally in the corresponding contralateral sensory-motor region and increased focally in the premotor part of the frontal lobe. The increase in the sensory region was attributed...

  2. Exercise Training Increases Parietal Lobe Cerebral Blood Flow in Chronic Stroke: An Observational Study

    Directory of Open Access Journals (Sweden)

    Andrew D. Robertson

    2017-09-01

    Full Text Available Exercise is increasingly recommended as an essential component of stroke rehabilitation, yet uncertainty remains with respect to its direct effect on the cerebral vasculature. The current study first demonstrated the repeatability of pseudo-continuous arterial spin labeling (ASL magnetic resonance imaging (MRI in older adults with stroke, and then investigated the change in cerebrovascular function following a 6-month cardiovascular rehabilitation program. In the repeatability study, 12 participants at least 3 months post-stroke underwent two ASL imaging scans 1 month apart. In the prospective observational study, eight individuals underwent ASL imaging and aerobic fitness testing before and after a 6-month cardiovascular rehabilitation program. Cerebral blood flow (CBF and the spatial coefficient of variation of CBF (sCoV were quantified to characterize tissue-level perfusion and large cerebral artery transit time properties, respectively. In repeat scanning, intraclass correlation (ICC indicated moderate test-retest reliability for global gray matter CBF (ICC = 0.73 and excellent reliability for sCoV (ICC = 0.94. In the observational study, gray matter CBF increased after training (baseline: 40 ± 13 vs. 6-month: 46 ± 12 ml·100 g−1·min−1, P = 0.036. The greatest change occurred in the parietal lobe (+18 ± 12%. Gray matter sCoV, however, did not change following training (P = 0.31. This study provides preliminary evidence that exercise-based rehabilitation in chronic stroke enhances tissue-level perfusion, without changing the relative hemodynamic properties of the large cerebral arteries.

  3. 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

    (2)) and following 6 h passive exposure to hypoxia (12% O(2)). Blood flow velocity in the middle cerebral artery (MCAv) and mean arterial blood pressure (MAP) were measured for determination of CA following calculation of transfer function analysis and rate of regulation (RoR). Nine subjects......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...

  4. Metabolic effects of fructose and the worldwide increase in obesity.

    Science.gov (United States)

    Tappy, Luc; Lê, Kim-Anne

    2010-01-01

    While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C(6)H(12)O(6)), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic

  5. Metabolic syndrome increases the risk of aggressive prostate cancer detection.

    Science.gov (United States)

    Morote, Juan; Ropero, Jordi; Planas, Jacques; Bastarós, Juan M; Delgado, Gueisy; Placer, José; Celma, Anna; de Torres, Inés M; Carles, Joan; Reventós, Jaume; Doll, Andreas

    2013-06-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Metabolic syndrome can identify patients at high risk of cardiovascular disease. The prevalence of metabolic syndrome is increasing worldwide and is associated with increased age, obesity and hypogonadism. The association between metabolic syndrome and prostate cancer development has not been studied comprehensively, and published studies report divergent results. This study indicates that tumours detected in men with metabolic syndrome are more aggressive than those detected in men without this condition. To further examine the association between metabolic syndrome (MS), prostate cancer (PC) detection risk and tumour aggressiveness. From 2006 to 2010, 2408 men not receiving 5α-reductase inhibitors were scheduled for prostatic biopsy due to PSA above 4 ng/mL and/or abnormal digital rectal examination. MS was evaluated according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition. Tumour aggressiveness was evaluated through biopsy Gleason score, clinical stage and risk of biochemical recurrence after primary treatment. The rates of PC detection were 34.5% and 36.4% respectively in men with and without MS, P = 0.185. High grade PC rates (Gleason score 8-10) were 35.9% and 23.9% respectively, P 20) were 38.5% and 33.0% respectively, P = 0.581. Multivariate analysis confirmed that MS was not associated with the risk of PC detection but it was associated with an increased risk of high grade tumours (odds ratio 1.75, 95% CI 1.26-2.41), P < 0.001. MS seems not be associated with an increased risk of PC detection but it is associated with an increased risk of more aggressive tumours. © 2012 BJU International.

  6. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism.

    Science.gov (United States)

    Rowlands, Benjamin D; Lau, Chew Ling; Ryall, James G; Thomas, Donald S; Klugmann, Matthias; Beart, Philip M; Rae, Caroline D

    2015-07-01

    Silent information regulators (SIRTs) have been shown to deacetylate a range of metabolic enzymes, including those in glycolysis and the Krebs cycle, and thus alter their activity. SIRTs require NAD(+) for their activity, linking cellular energy status to enzyme activity. To examine the impact of SIRT1 modulation on oxidative metabolism, this study tests the effect of ligands that are either SIRT-activating compounds (resveratrol and SRT1720) or SIRT inhibitors (EX527) on the metabolism of (13)C-enriched substrates by guinea pig brain cortical tissue slices with (13)C and (1)H nuclear magnetic resonance spectroscopy. Resveratrol increased lactate labeling but decreased incorporation of (13)C into Krebs cycle intermediates, consistent with effects on AMPK and inhibition of the F0/F1-ATPase. By testing with resveratrol that was directly applied to astrocytes with a Seahorse analyzer, increased glycolytic shift and increased mitochondrial proton leak resulting from interactions of resveratrol with the mitochondrial electron transport chain were revealed. SRT1720, by contrast, stimulated incorporation of (13)C into Krebs cycle intermediates and reduced incorporation into lactate, although the inhibitor EX527 paradoxically also increased Krebs cycle (13)C incorporation. In summary, the various SIRT1 modulators show distinct acute effects on oxidative metabolism. The strong effects of resveratrol on the mitochondrial respiratory chain and on glycolysis suggest that caution should be used in attempts to increase bioavailability of this compound in the CNS.

  7. Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2012-05-01

    Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism, especially in tyrosinemia type II, which is caused by deficiency of tyrosine aminotransferase and provokes eyes, skin, and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in this study, we investigated the in vivo and in vitro effects of tyrosine on some parameters of energy metabolism in cerebral cortex of 14-day-old Wistar rats. We observed that 2 mM tyrosine inhibited in vitro the pyruvate kinase (PK) activity and that this inhibition was prevented by 1 mM reduced glutathione with 30, 60, and 90 min of preincubation. Moreover, administration of tyrosine methyl ester (TME) (0.5 mg/g of body weight) decreased the activity of PK and this reduction was prevented by pre-treatment with creatine (Cr). On the other hand, tyrosine did not alter adenylate kinase (AK) activity in vitro, but administration of TME enhanced AK activity not prevented by Cr pre-treatment. Finally, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions and this diminution was prevented by Cr pre-treatment. The results suggest that tyrosine alters essential sulfhydryl groups necessary for CK and PK functions, possibly through oxidative stress. In case this also occurs in the patients, it is possible that energy metabolism alterations may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias.

  8. Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients---a PET-CT cerebral functional imaging study

    Directory of Open Access Journals (Sweden)

    Huang Yong

    2012-06-01

    Full Text Available Abstract Background Acupuncture has been applied to aid in the recovery of post-stroke patients, but its mechanism is unclear. This study aims to analyze the relationship between acupuncture and glucose metabolism in cerebral functional regions in post-stroke patients using 18 FDG PET-CT techniques. Forty-three ischemic stroke patients were randomly divided into 5 groups: the Waiguan (TE5 needling group, the TE5 sham needling group, the sham point needling group, the sham point sham needling group and the non-needling group. Cerebral functional images of all patients were then acquired using PET-CT scans and processed by SPM2 software. Results Compared with the non-needling group, sham needling at TE5 and needling/sham needling at the sham point did not activate cerebral areas. However, needling at TE5 resulted in the activation of Brodmann Area (BA 30. Needling/sham needling at TE5 and needling at the sham point did not deactivate any cerebral areas, whereas sham needling at the sham point led to deactivation in BA6. Compared with sham needling at TE5, needling at TE5 activated BA13, 19 and 47 and did not deactivate any areas. Compared with needling at the sham point, needling at TE5 had no associated activation but a deactivating effect on BA9. Conclusion Needling at TE5 had a regulating effect on cerebral functional areas shown by PET-CT, and this may relate to its impact on the recovery of post-stroke patients.

  9. Gender differences in age-related decline in regional cerebral glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  10. 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.

  11. Adult-onset hypothyroidism and the cerebral metabolism of (1,2-13C2) acetate as detected by 13C nuclear magnetic resonance.

    Science.gov (United States)

    Chapa, F; Künnecke, B; Calvo, R; Escobar del Rey, F; Morreale de Escobar, G; Cerdán, S

    1995-01-01

    The effects of adult-onset hypothyroidism on the metabolic compartmentation of the cerebral tricarboxylic acid cycle and the gamma-aminobutyric acid (GABA) shunt have been investigated by 13C nuclear magnetic resonance spectroscopy. Rats thyroidectomized as adults and age-matched controls were infused in the right jugular vein with unlabeled or (1,2-13C2) acetate solutions for 60 min. At the end of the infusion, the brains were frozen in situ and perchloric acid extracts were prepared and analyzed by 13C nuclear magnetic resonance and reverse-phase HPLC. Thyroidectomized animals showed a decrease in the incorporation of 13C from (1,2-13C2) acetate in cerebral metabolites and an increase in the concentrations of unlabeled glutamate and GABA. Computer-assisted interpretation of the 13C multiplets observed for the carbons of glutamate, glutamine, and GABA indicated that adult-onset hypothyroidism produced 1) a decrease in the contribution of infused (1,2-13C2) acetate to the glial tricarboxylic acid cycle; 2) an increase in the contribution of unlabeled acetyl-CoA to the neuronal tricarboxylic acid cycle; and 3) impairments in the exchange of glutamate, glutamine, and GABA between the neuronal and glial compartments. Despite the fact that the adult brain has often been considered metabolically unresponsive to thyroid hormone status, present results show metabolic alterations in the neuronal and glial compartments that are reversible with substitution therapy.

  12. Attenuation of γ-aminobutyric acid (GABA) transaminase activity contributes to GABA increase in the cerebral cortex of mice exposed to β-cypermethrin.

    Science.gov (United States)

    Han, Y; Cao, D; Li, X; Zhang, R; Yu, F; Ren, Y; An, L

    2014-03-01

    The current study investigated the γ-aminobutyric acid (GABA) levels and GABA metabolic enzymes (GABA transaminase (GABA(T)) and glutamate decarboxylase (GAD)) activities at 2 and 4 h after treatment, using a high-performance liquid chromatography with ultraviolet detectors and colorimetric assay, in the cerebral cortex of mice treated with 20, 40 or 80 mg/kg β-cypermethrin by a single oral gavage, with corn oil as vehicle control. In addition, GABA protein (4 h after treatment), GABA(T) protein (2 h after treatment) and GABA receptors messenger RNA (mRNA) expression were detected by immunohistochemistry, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction, respectively. β-Cypermethrin (80 mg/kg) significantly increased GABA levels in the cerebral cortex of mice, at both 2 and 4 h after treatment, compared with the control. Also, GABA immunohistochemistry results suggested that the number of positive granules was increased in the cerebral cortex of mice 4 h after exposure to 80 mg/kg β-cypermethrin when compared with the control. Furthermore, the results also showed that GABA(T) activity detected was significantly decreased in the cerebral cortex of mice 2 h after β-cypermethrin administration (40 or 80 mg/kg). No significant changes were found in GAD activity, or the expression of GABA(T) protein and GABAB receptors mRNA, in the cerebral cortex of mice, except that 80 mg/kg β-cypermethrin caused a significant decrease, compared with the vehicle control, in GABAA receptors mRNA expression 4 h after administration. These results suggested that attenuated GABA(T) activity induced by β-cypermethrin contributed to increased GABA levels in the mouse brain. The downregulated GABAA receptors mRNA expression is most likely a downstream event.

  13. Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine.

    Science.gov (United States)

    Phelps, M E

    1981-01-01

    The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on

  14. Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.

    Science.gov (United States)

    Nofzinger, E A; Price, J C; Meltzer, C C; Buysse, D J; Villemagne, V L; Miewald, J M; Sembrat, R C; Steppe, D A; Kupfer, D J

    2000-04-10

    This study sought to clarify the neurobiological basis of variations in one aspect of central nervous system 'arousal' in depression by characterizing the functional neuroanatomic correlates of beta electroencephalographic (EEG) power density during non-rapid eye movement (NREM) sleep. First, nine healthy (n=9) subjects underwent concurrent EEG sleep studies and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans during their first NREM period of sleep in order to generate hypotheses about specific brain structures that show a relationship between increased beta power and increased relative glucose metabolism. Second, brain structures identified in the healthy subjects were then used as a priori regions of interest in similar analyses from identical studies in 12 depressed subjects. Statistical parametric mapping was used to identify the relationship between beta power and relative regional cerebral glucose metabolism (rCMRglu) during NREM sleep. Regions that demonstrated significant correlations between beta power and relative cerebral glucose metabolism in both the healthy and depressed subjects included the ventromedial prefrontal cortex and the right lateral inferior occipital cortex. During a baseline night of sleep, depressed patients demonstrated a trend toward greater beta power in relation to a separate age- and gender-matched healthy control group. In both healthy and depressed subjects, beta power negatively correlated with subjective sleep quality. Finally, in the depressed group, there was a trend for beta power to correlate with an indirect measure of absolute whole brain metabolism during NREM sleep. This study demonstrates a similar relationship between electrophysiological arousal and glucose metabolism in the ventromedial prefrontal cortex in depressed and healthy subjects. Given the increased electrophysiological arousal in some depressed patients and the known anatomical relations between the ventromedial

  15. Physiological activation of the human cerebral cortex during auditory perception and speech revealed by regional increases in cerebral blood flow

    DEFF Research Database (Denmark)

    Lassen, N A; Friberg, L

    1988-01-01

    by measuring regional cerebral blood flow CBF after intracarotid Xenon-133 injection are reviewed with emphasis on tests involving auditory perception and speech, and approach allowing to visualize Wernicke and Broca's areas and their contralateral homologues in vivo. The completely atraumatic tomographic CBF...

  16. Increased 20-HETE synthesis explains reduced cerebral blood flow but not impaired neurovascular coupling after cortical spreading depression in rat cerebral cortex

    DEFF Research Database (Denmark)

    Fordsmann, Jonas Christoffer; ko, Rebecca; Choi, Hyun B

    2013-01-01

    Cortical spreading depression (CSD) is associated with release of arachidonic acid (AA), impaired neurovascular coupling, and reduced cerebral blood flow (CBF), caused by cortical vasoconstriction. We tested the hypothesis that the released AA is metabolized by the cytochrome P450 enzyme to produce...... neurovascular coupling after CSD. These findings suggest that CSD-induced increments in 20-HETE cause the reduction in CBF after CSD, and that the attenuation of stimulation-induced CBF responses after CSD has a different mechanism. We suggest that blockade of 20-HETE synthesis may be clinically relevant...

  17. Decreased cerebral metabolism in stroke-prone spontaneously hypertensive rats (SHRSP) with stroke and its possible improvement by Solcoseryl.

    Science.gov (United States)

    Yamasaki, Y; Yamamoto, Y; Senga, Y; Isogai, M; Shimizu, H; Yamori, Y

    1991-01-01

    Local cerebral glucose utilization (LCGU) was decreased in SHRSP with stroke compared with normotensive Wistar rats. The decrement of LCGU was less in Solcoseryl-treated SHRSP with stroke than that in saline-treated SHRSP with stroke and these brain areas where LCGU was less damaged, in Solcoseryl-treated SHRSP were consistent with the important functioning sites of emotion, motor movement and memory. The result suggests that Solcoseryl may be useful for metabolic improvement of the brain damage after stroke.

  18. Non-vitamin k antagonist oral anticoagulants do not increase cerebral microbleeds.

    Science.gov (United States)

    Saito, Tsukasa; Kawamura, Yuichiro; Sato, Nobuyuki; Kano, Kohei; Takahashi, Kae; Asanome, Asuka; Sawada, Jun; Katayama, Takayuki; Hasebe, Naoyuki

    2015-06-01

    Atrial fibrillation (AF) is a cardiac arrhythmia that frequently induces ischemic strokes. Nowadays, non-vitamin K antagonist oral anticoagulants (NOACs) have come into widespread use for cardiogenic embolism prevention in place of warfarin. Recently, cerebral microbleeds (CMBs) have been noticed for their potential implication in cerebral small vessel disease. We hypothesized that NOACs do not have an unfavorable influence over cerebral small vessels and investigated whether NOACs increase CMBs in AF patients in a prospective manner. We performed baseline magnetic resonance imaging (MRI) examinations on the 69 enrolled AF patients and re-examined second round of MRI 1 year later. The enrolled patients continued the same anticoagulation therapy during the meantime. CMBs did not develop in the 23 patients with NOACs for 1 year. Nine patients with antiplatelets also did not develop CMBs. On the other hand, 3 of 21 patients continued on warfarin and 3 of 9 with warfarin and antiplatelets had CMBs. When divided into 2 groups according to whether the CMBs developed, significant differences in the incidence of using NOACs were observed between the 2 groups (P = .02). A multivariate regression analysis showed that warfarin was independently related to the new development of CMBs (hazard ratio, 10.75; 95% confidence interval, 1.22-94.99; P = .03). This is the first report to clarify that NOACs do not increase CMBs in AF patients longitudinally in 1 year. Further consideration will be continued with a much longer follow-up in large samples. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Time courses of behavioral and regional cerebral metabolic responses to different doses of meta-chlorophenylpiperazine in awake rats.

    Science.gov (United States)

    Freo, U; Soncrant, T T; Ricchieri, G L; Wozniak, K M; Larson, D M; Rapoport, S I

    1990-03-19

    The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15-30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.

  20. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    Science.gov (United States)

    Balestri, P; Lucignani, G; Fois, A; Magliani, L; Calistri, L; Grana, C; Di Bartolo, R M; Perani, D; Fazio, F

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal. Images PMID:7798976

  1. 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.).

  2. 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.

  3. Dramatic Increase in Cerebral Blood Flow following Soman Intoxication If Signs of Symptoms Can Be Seen

    Directory of Open Access Journals (Sweden)

    Ann Göransson Nyberg

    2015-01-01

    Full Text Available Organophosphate poisoning is associated with adverse effects on the central nervous system such as seizure/convulsive activity and long term changes in neuronal networks. This study report an investigation designed to assess the consequences of Soman, a highly toxic organophosphorus compound, exposure on regional blood flow in the rat brain and peripheral organs. We performed repeated blood flow measurements in the same animal, using the microspheres technique, to characterize changes in regional blood flow at different times after Soman intoxication. In addition, the cardiopulmonary effects of Soman were followed during the intoxication. Administration of Soman (1 LD50; 90 µg/kg, s.c. to anaesthetized rats produced a decrease in blood acetylcholinesterase activity in all animals tested. Although, only six out of ten rats showed signs of poisoning like a decrease in respiratory rate, the results show that only animals with significant signs of poisoning demonstrated an increase in cerebral blood flow. We conclude that it is of great importance to treat all data individually. An overall mean can easily be misinterpreted and conceal important effects. We also conclude that the increase in cerebral blood flow has an important role in the effect on respiration and that this effect is independent of the blood acetylcholinesterase activity.

  4. Voxel based statistical analysis method for microPET studies to assess the cerebral glucose metabolism in cat deafness model: comparison to ROI based method

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Lee, Jong Jin; Kang, Hye Jin; Lee, Hyo Jeong; Oh, Seung Ha; Kim, Chong Sun; Jung, June Key; Lee, Myung Chul; Lee, Dong Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of)

    2005-07-01

    Imaging research on the brain of sensory-deprived cats using small animal PET scanner has gained interest since the abundant information about the sensory system of ths animal is available and close examination of the brain is possible due to larger size of its brain than mouse or rat. In this study, we have established the procedures for 3D voxel-based statistical analysis (SPM) of FDG PET image of cat brain, and confirmed using ROI based-method. FDG PET scans of 4 normal and 4 deaf cats were acquired for 30 minutes using microPET R4 scanner. Only the brain cortices were extracted using a masking and threshold method to facilitate spatial normalization. After spatial normalization and smoothing, 3D voxel-wise and ROI based t-test were performed to identify the regions with significant different FDG uptake between the normal and deaf cats. In ROI analysis, 26 ROIs were drawn on both hemispheres, and regional mean pixel value in each ROI was normalized to the global mean of the brain. Cat brains were spatially normalized well onto the target brain due to the removal of background activity. When cerebral glucose metabolism of deaf cats were compared to the normal controls after removing the effects of the global count, the glucose metabolism in the auditory cortex, head of caudate nucleus, and thalamus in both hemispheres of the deaf cats was significantly lower than that of the controls (P<0.01). No area showed a significantly increased metabolism in the deaf cats even in higher significance level (P<0.05). ROI analysis also showed significant reduction of glucose metabolism in the same region. This study established and confirmed a method for voxel-based analysis of animal PET data of cat brain, which showed high localization accuracy and specificity and was useful for examining the cerebral glucose metabolism in a cat cortical deafness model.

  5. Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Peng, N.J.; Tsay, D.G. [Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung (Taiwan); Liu, R.S. [Department of Nuclear Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei (Taiwan); Li, J.Y.; Kong, K.W. [Division of Neurology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung (Taiwan); Kwok, C.G.; Strauss, H.W. [Division of Nuclear Medicine, Department of Radiology, Stanford University Medical Center, CA (United States)

    2000-01-01

    We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid. (orig.)

  6. Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.

    Science.gov (United States)

    Wang, Qiaoli; Han, Xiaotong; Li, Jian; Gao, Xinghui; Wang, Yan; Liu, Mingzhou; Dong, Guicheng; Yue, Jiang

    2015-04-01

    1. Cytochrome P450 2D (CYP2D) protein is widely expressed across brain regions in human and rodents. We investigated the interactions between tramadol, a clinically used analgesic, and brain CYP2D regulators, by establishing concentration-time curves of tramadol and O-desmethyltramadol (M1) in rat cerebrospinal fluid (CSF) and plasma, as well as by analyzing the analgesia-time course of tramadol. 2. Propranolol (20 μg, intracerebroventricular injection), CYP2D inhibitor, prolonged the elimination t1/2 of tramadol (40 mg/kg, intraperitoneal injection) in the CSF; meanwhile, lower Cmax and AUC0-∞ values of M1 were observed. Nicotine (1 mg base/kg, subcutaneous injection, seven days), brain CYP2D inducer, induced a shorter Tmax and elevated Cmax of M1 in CSF. No differences in the peripheral metabolism of tramadol were observed following propranolol and nicotine pretreatment. Nicotine increased areas under the analgesia-time curve (AUC) for 0-45 min and 0-90 min of tramadol, which was attenuated by propranolol administration. The analgesic actions of tramadol positively correlated with cerebral M1 concentration. 3. The results suggest that the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions (DDIs) of tramadol. Brain CYPs may play an important role in DDIs of centrally active substances.

  7. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

    Science.gov (United States)

    Nofzinger, Eric A; Buysse, Daniel J; Miewald, Jean M; Meltzer, Carolyn C; Price, Julie C; Sembrat, Robert C; Ombao, Hernando; Reynolds, Charles F; Monk, Timothy H; Hall, Martica; Kupfer, David J; Moore, Robert Y

    2002-05-01

    Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain

  8. Alterations in local cerebral glucose metabolism and endogenous thyrotropin-releasing hormone levels in rolling mouse Nagoya and effect of thyrotropin-releasing hormone tartrate.

    Science.gov (United States)

    Nakayama, T; Nagai, Y

    1996-11-01

    To identify the brain region(s) responsible for the expression of ataxic gaits in an ataxic mutant mouse model, Rolling mouse Nagoya (RMN), changes in local cerebral glucose metabolism in various brain regions and the effect of thyrotropin-releasing hormone tartrate (TRH-T), together with alterations in endogenous thyrotropin-releasing hormone (TRH) levels in the brains of RMN, were investigated. Ataxic mice [RMN (rol/rol)] showed significant decreases in glucose metabolism in regions of the diencephalon: thalamic dorsomedial nucleus, lateral geniculate body and superior colliculus; brain stem: substantia nigra, raphe nucleus and vestibular nucleus; and cerebellar nucleus as compared with normal controls [RMN (+/+)]. When RMN (rol/rol) was treated with TRH-T (10 mg/kg, equivalent to 7 mg/kg free TRH), glucose metabolism was significantly increased in these regions. These results suggest that these regions may be responsible for ataxia. We also found that TRH levels in the cerebellum and brain stem of RMN (rol/rol) were significantly higher than those of RMN (+/+). These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them.

  9. Increased susceptibility to pentylenetetrazol following survival of cerebral malaria in mice.

    Science.gov (United States)

    Grauncke, Ana C B; Souza, Thaíze L; Ribeiro, Leandro R; Brant, Fátima; Machado, Fabiana S; Oliveira, Mauro S

    2016-07-01

    Malaria is considered a neglected disease and public health problem, affecting >200 million people worldwide. In the present study we used the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria (CM) in C57BL/6 mice. After rescue from CM and parasite clearance, animals were submitted to a seizure susceptibility test (45 days after infection) using a low dose of pentylenetetrazol (PTZ, 30 mg/kg) and monitored with use of behavioral and electroencephalography (EEG) methods. Mice rescued from CM presented a reduced latency to myoclonic and tonic-clonic seizures and an increased duration of tonic-clonic seizures. In addition, quantitative analysis of EEG revealed a decrease in relative power at beta frequency band in PbA-infected animals after PTZ injection. Our results suggest that CM may lead to increased susceptibility to seizures in mice.

  10. Multiplicity and early gestational age contribute to an increased risk of cerebral palsy from assisted conception

    DEFF Research Database (Denmark)

    Hvidtjørn, Dorte; Grove, Jakob; Schendel, Diana;

    2010-01-01

    : The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants....... When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. CONCLUSION......BACKGROUND: This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). METHODS: This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception...

  11. 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.

  12. 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 exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, 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 .

  13. Increased cerebral oxygen extraction capacity in patients with Alzheimer’s disease

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Gyldensted, Louise; Nagenthiraja, Kartheeban

    the metabolic requirements of the brain tissues. In this study we investigated the brain oxygen extraction capacity (OEFmax) in AD patients and controls using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI). Increased OEFmax was detected in the temporal, parietal and frontal lobes of AD...

  14. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  15. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Emese Prandovszky

    Full Text Available The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.

  16. 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.

  17. Gamma knife irradiation increases cerebral endothelial expression of intercellular adhesion molecule 1 and E-selectin.

    Science.gov (United States)

    Sharp, Christopher D; Jawahar, Ajay; Warren, April C; Elrod, John W; Nanda, Anil; Alexander, J Steven

    2003-07-01

    Alterations in multiple functions of the microvasculature occur in response to gamma irradiation and are thought to contribute to radiation-induced end organ damage by inducing inflammatory responses, particularly leukocyte infiltration into the affected area. Endothelial cell adhesion molecules (ECAMs) mediate leukocyte adhesion and migration. Here, we validate a method to study the effect of Leksell gamma knife stereotactic radiosurgery on the expression of ECAMs on human cerebral endothelium at 0, 24, 48, and 72 hours after irradiation. A human brain endothelial cell line (IHEC) was cultured on 12-mm coverslips and subjected to 50 Gy of collimated gamma irradiation with the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Lactate dehydrogenase release was measured at 24, 48, and 72 hours after irradiation and caspase-3 at 24, 48, 72, 96, and 120 hours. ECAM expression was measured at postirradiation intervals of 0, 24, 48, and 72 hours by cell enzyme-linked immunoabsorbent assay. We used a cell irradiator composed of two chambers. The upper chamber holds the coverslips firmly in place while they are immersed in media. The lower chamber is connected to a peristaltic pump, which pumps water into the chamber and maintains the media in the upper chamber at 37 degrees C through convection. None of the ECAMs tested was significantly elevated compared with the control basally. Twenty-four hours after irradiation, intercellular adhesion molecule 1 was significantly elevated on brain endothelial cells but there was no significant elevation of E-selectin. Vascular cell adhesion molecule 1 was increased slightly but not significantly and decreased at 48 hours. At 72 hours, E-selectin expression was significantly increased; intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were not altered relative to sham controls. Increased ECAM expression and lactate dehydrogenase release support the idea that the cerebral microvasculature undergoes an

  18. Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy?

    Science.gov (United States)

    Boas, D. A.; Strangman, G.; Culver, J. P.; Hoge, R. D.; Jasdzewski, G.; Poldrack, R. A.; Rosen, B. R.; Mandeville, J. B.

    2003-08-01

    We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO2) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on a Windkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO2 change. An absolute estimate is also confounded by uncertainty in the flow-volume relationship. However, the ratio of the flow change to the CMRO2 change is relatively insensitive to these uncertainties. For the finger tapping task, we estimate a most probable flow-consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow-consumption ratio will require better estimates of the model parameters or flow information, as can be provided by combining NIRS with fMRI.

  19. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Heqin Zhan

    2014-01-01

    Full Text Available Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF and neurotrophin-3 (NT-3 were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05 , P < 0.01. LGB significantly increased NGF and NT-3 mRNA (messenger RNA and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01. Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.

  20. Determinants of increased cardiovascular disease in obesity and metabolic syndrome.

    Science.gov (United States)

    Vazzana, N; Santilli, F; Sestili, S; Cuccurullo, C; Davi, G

    2011-01-01

    Obesity is associated with an increased mortality and morbidity for cardiovascular disease (CVD) and adipose tissue is recognised as an important player in obesity-mediated CVD. The diagnosis of the metabolic syndrome (MS) appears to identify substantial additional cardiovascular risk above and beyond the individual risk factors, even though the pathophysiology underlying this evidence is still unravelled. The inflammatory response related to fat accumulation may influence cardiovascular risk through its involvement not only in body weight homeostasis, but also in coagulation, fibrinolysis, endothelial dysfunction, insulin resistance (IR) and atherosclerosis. Moreover, there is evidence that oxidative stress may be a mechanistic link between several components of MS and CVD, through its role in inflammation and its ability to disrupt insulin-signaling. The cross-talk between impaired insulin-signaling and inflammatory pathways enhances both metabolic IR and endothelial dysfunction, which synergize to predispose to CVD. Persistent platelet hyperreactivity/activation emerges as the final pathway driven by intertwined interactions among IR, adipokine release, inflammation, dyslipidemia and oxidative stress and provides a pathophysiological explanation for the excess risk of atherothrombosis in this setting. Despite the availability of multiple interventions to counteract these metabolic changes, including appropriate diet, regular exercise, antiobesity drugs and bariatric surgery, relative failure to control the incidence of MS and its complications reflects both the multifactorial nature of these diseases as well as the scarce compliance of patients to established strategies. Evaluation of the impact of these therapeutic strategies on the pathobiology of atherothrombosis, as discussed in this review, will translate into an optimized approach for cardiovascular prevention.

  1. Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in chronic alcoholics: a positron emission tomography study corrected for cerebral atrophy.

    Directory of Open Access Journals (Sweden)

    John C Umhau

    Full Text Available OBJECTIVE: Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3, particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics. METHODS: We compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET, we measured regional coefficients (K* and rates (J(in of DHA incorporation from plasma into the brain of each group using [1-(11C]DHA, and regional cerebral blood flow (rCBF using [(15O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified. RESULTS: Mean K* for DHA was significantly and widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain J(in, the product of K* and unesterified plasma DHA concentration. DISCUSSION: Significantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

  2. Magnetic stimulation at Neiguan (PC6) acupoint increases connections between cerebral cortex regions

    Institute of Scientific and Technical Information of China (English)

    Hong-li Yu; Gui-zhi Xu; Lei Guo; Ling-di Fu; Shuo Yang; Shuo Shi; Hua Lv

    2016-01-01

    Stimulation at speciifc acupoints can activate cortical regions in human subjects. Previous studies have mainly focused on a single brain region. However, the brain is a network and many brain regions participate in the same task. The study of a single brain region alone cannot clearly explain any brain-related issues. Therefore, for the present study, magnetic stimulation was used to stimulate the Neiguan (PC6) acu-point, and 32-channel electroencephalography data were recorded before and after stimulation. Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitabil-ity. Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.

  3. Serum Resistin Levels May Contribute to an Increased Risk of Acute Cerebral Infarction.

    Science.gov (United States)

    Dong, Xiao-Liu; Xu, Shi-Jun; Zhang, Li; Zhang, Xiu-Qing; Liu, Ting; Gao, Qiu-Yan; Qian, Qing-Qiang; Sun, Bao-Liang; Yang, Ming-Feng

    2017-04-01

    The objective of this study was to investigate the association between serum resistin levels and acute cerebral infarction (ACI). PubMed, SpringerLink, Wiley, EBSCO, Ovid, Web of Science, Wanfang, China National Knowledge Infrastructure, and VIP databases (last updated search in October 2014) were exhaustively searched, and data from the eligible studies were extracted and analyzed to assess the association between serum resistin levels and ACI. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for data analysis. Ten studies including 1829 ACI patients and 1557 healthy controls were eligible for inclusion in the meta-analysis. Our major result revealed that ACI patients exhibited higher serum resistin levels compared with healthy controls. Asubgroup analysis based on ethnicity showed a significant association between serum resistin levels and ACI in Asians, but surprisingly not in Caucasians. The results of our meta-analysis suggest that serum resistin levels are associated with an increased risk of ACI.

  4. Paradoxical presentation of orthostatic headache associated with increased intracranial pressure in patients with cerebral venous thrombosis

    Directory of Open Access Journals (Sweden)

    Jung B Kim

    2013-01-01

    Full Text Available Headache is the most common symptom of cerebral venous thrombosis (CVT; however, the detailed underlying mechanisms and characteristics of headache in CVT have not been well described. Here, we report two cases of CVT whose primary and lasting presentation was orthostatic headache, suggestive of decreased intracranial pressure. Contrary to our expectations, the headaches were associated with elevated cerebrospinal fluid (CSF pressure. Magnetic resonance imaging and magnetic resonance venography showed characteristic voiding defects consistent with CVT. We suggest that orthostatic headache can be developed in a condition of decreased intracranial CSF volume in both intracranial hypotensive and intracranial hypertensive states. In these cases, orthostatic headache in CVT might be caused by decreased intracranial CSF volume that leads to the inferior displacement of the brain and traction on pain-sensitive intracranial vessels, despite increased CSF pressure on measurement. CVT should be considered in the differential diagnosis when a patient complains of orthostatic headache.

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

    OpenAIRE

    Laura Mellendijk; Maximilian Wiesmann; Kiliaan, Amanda J

    2015-01-01

    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 M...

  6. Carotid stenting for unilateral stenosis can increase contralateral hemispheric cerebral blood flow.

    Science.gov (United States)

    Sadato, Akiyo; Maeda, Shingo; Hayakawa, Motoharu; Adachi, Kazuhide; Toyama, Hiroshi; Nakahara, Ichiro; Hirose, Yuichi

    2017-07-12

    The revascularization of carotid stenosis can increase ipsilateral cerebral blood flow (CBF). Occasionally, elevated CBF is also evident on the contralateral side, but this phenomenon is poorly understood. To analyze retrospectively the relationship between a contralateral CBF increase and several clinical and radiologic features. We retrospectively analyzed 40 patients with unilateral cervical carotid stenosis treated by carotid artery stenting (CAS). Using (123)I-iodamphetamine single-photon emission computed tomography (SPECT); we compared pre- and postoperative hemispheric CBF on both sides. We investigated the influence of the following five factors on the increase of the contralateral hemispheric CBF: stenosis grade (≥50% or increased significantly on both sides: from 33.4±5.6 (mean ± SD) to 38.7±7.8 mL/min on the operated side (paired t test, pincrease of the CBF on the contralateral side (p=0.03). Revascularization by CAS for unilateral carotid stenosis can increase hemispheric CBF on both sides. Increase of the contralateral CBF is correlated with stenosis grade (≥50%). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. 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.

  8. Coupling of cerebral blood flow and oxygen metabolism is conserved for chromatic and luminance stimuli in human visual cortex.

    Science.gov (United States)

    Leontiev, Oleg; Buracas, Giedrius T; Liang, Christine; Ances, Beau M; Perthen, Joanna E; Shmuel, Amir; Buxton, Richard B

    2013-03-01

    The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation is a critical determinant of the magnitude of the blood oxygenation level dependent (BOLD) response measured with functional magnetic resonance imaging (fMRI). Cytochrome oxidase (CO), a key component of oxidative metabolism in the mitochondria, is non-uniformly distributed in visual area V1 in distinct blob and interblob regions, suggesting significant spatial variation in the capacity for oxygen metabolism. The goal of this study was to test whether CBF/CMRO(2) coupling differed when these subpopulations of neurons were preferentially stimulated, using chromatic and luminance stimuli to preferentially stimulate either the blob or interblob regions. A dual-echo spiral arterial spin labeling (ASL) technique was used to measure CBF and BOLD responses simultaneously in 7 healthy human subjects. When the stimulus contrast levels were adjusted to evoke similar CBF responses (mean 65.4% ± 19.0% and 64.6% ± 19.9%, respectively for chromatic and luminance contrast), the BOLD responses were remarkably similar (1.57% ± 0.39% and 1.59% ± 0.35%) for both types of stimuli. We conclude that CBF-CMRO(2) coupling is conserved for the chromatic and luminance stimuli used, suggesting a consistent coupling for blob and inter-blob neuronal populations despite the difference in CO concentration.

  9. DOES RECTUS FEMORIS TRANSFER INCREASE KNEE FLEXION DURING STANCE PHASE IN CEREBRAL PALSY?

    Science.gov (United States)

    de Morais, Mauro César; Blumetti, Francesco Camara; Kawamura, Cátia Miyuki; Lopes, José Augusto Fernandes; Neves, Daniella Lins; Cardoso, Michelle de Oliveira

    2016-01-01

    ABSTRACT Objective: To evaluate whether distal rectus femoris transfer (DRFT) is related to postoperative increase of knee flexion during the stance phase in cerebral palsy (CP). Methods: The inclusion criteria were Gross Motor Function Classification System (GMFCS) levels I-III, kinematic criteria for stiff-knee gait at baseline, and individuals who underwent orthopaedic surgery and had gait analyses performed before and after intervention. The patients included were divided into the following two groups: NO-DRFT (133 patients), which included patients who underwent orthopaedic surgery without DRFT, and DRFT (83 patients), which included patients who underwent orthopaedic surgery that included DRFT. The primary outcome was to evaluate in each group if minimum knee flexion in stance phase (FMJFA) changed after treatment. Results: The mean FMJFA increased from 13.19° to 16.74° (p=0.003) and from 10.60° to 14.80° (p=0.001) in Groups NO-DRFT and DRFT, respectively. The post-operative FMJFA was similar between groups NO-DRFT and DRFT (p=0.534). The increase of FMJFA during the second exam (from 13.01° to 22.51°) was higher among the GMFCS III patients in the DRFT group (p<0.001). Conclusion: In this study, DRFT did not generate additional increase of knee flexion during stance phase when compared to the control group. Level of Evidence III, Retrospective Comparative Study. PMID:26997910

  10. Sleep deprivation increases cerebral serotonin 2A receptor binding in humans.

    Science.gov (United States)

    Elmenhorst, David; Kroll, Tina; Matusch, Andreas; Bauer, Andreas

    2012-12-01

    Serotonin and its cerebral receptors play an important role in sleep-wake regulation. The aim of the current study is to investigate the effect of 24-h total sleep deprivation on the apparent serotonin 2A receptor (5-HT(2A)R) binding capacity in the human brain to test the hypothesis that sleep deprivation induces global molecular alterations in the cortical serotonergic receptor system. Volunteers were tested twice with the subtype-selective radiotracer [(18)F]altanserin and positron emission tomography (PET) for imaging of 5-HT(2A)Rs at baseline and after 24 h of sleep deprivation. [(18)F]Altanserin binding potentials were analyzed in 13 neocortical regions of interest. The efficacy of sleep deprivation was assessed by questionnaires, waking electroencephalography, and cognitive performance measurements. Sleep laboratory and neuroimaging center. Eighteen healthy volunteers. Sleep deprivation. A total of 24 hours of sleep deprivation led to a 9.6% increase of [(18)F]altanserin binding on neocortical 5-HT(2A) receptors. Significant region-specific increases were found in the medial inferior frontal gyrus, insula, and anterior cingulate, parietal, sensomotoric, and ventrolateral prefrontal cortices. This study demonstrates that a single night of total sleep deprivation causes significant increases of 5-HT(2A)R binding potentials in a variety of cortical regions although the increase declines as sleep deprivation continued. It provides in vivo evidence that total sleep deprivation induces adaptive processes in the serotonergic system of the human brain.

  11. 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

    community-acquired meningitis utilizing intracerebral microdialysis and bedside biochemical analysis. According to previous studies, cerebral ischemia was defined as lactate/pyruvate (LP) ratio >30 with intracerebral pyruvate level

  12. 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...

  13. Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

    Science.gov (United States)

    Shams, Sara; Granberg, Tobias; Martola, Juha; Li, Xiaozhen; Shams, Mana; Fereshtehnejad, Seyed-Mohammad; Cavallin, Lena; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Wahlund, Lars-Olof

    2016-03-01

    Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p CMBs (p CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer's disease (p CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs. © The Author(s) 2015.

  14. 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

  15. Increased prevalence of metabolic syndrome in patients with acne inversa.

    Directory of Open Access Journals (Sweden)

    Robert Sabat

    Full Text Available BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88, hypertriglyceridemia (odds ratio 2.24, hypo-HDL-cholesterolemia (odds ratio 4.56, and hyperglycemia (odds ratio 4.09 in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001. AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend

  16. Increasing Physical Activity Decreases Hepatic Fat and Metabolic Risk Factors.

    Science.gov (United States)

    Alderete, Tanya L; Gyllenhammer, Lauren E; Byrd-Williams, Courtney E; Spruijt-Metz, Donna; Goran, Michael I; Davis, Jaimie N

    2012-04-01

    This study assessed the changes in time spent in moderate to vigorous physical activity (MVPA) on fat depots, insulin action, and inflammation. Longitudinal data were generated from 66 Hispanic adolescents (15.6±1.1 yr; BMI percentile 97.1±3.0) who participated in a 16-wk nutrition or nutrition+exercise intervention. There were no effects of the intervention on PA, but there were inter-individual changes in PA. For purposes of this analysis, all intervention groups were combined to assess how changes in PA during 16 wk affected changes in adiposity, insulin action, and markers of inflammation. MVPA was assessed by 7-day accelerometry, total body fat via DXA, liver fat by MRI, and insulin, glucose and HOMA-IR via a fasting blood draw. A repeated measures ANCOVA was used to assess the effect of MVPA on fat depots, insulin action, and inflammatory markers. Sixty-two percent of participants increased MVPA (mean increase, 19.7±16.5 min/day) and 38% decreased MVPA (mean decrease, 10.7±10.1 min/day). Those who increased MVPA by as little as 20 min per day over 16 wk, compared to those who decreased MVPA, had significant reductions in liver fat (-13% vs. +3%; P=0.01), leptin levels (-18% vs. +4%; P=0.02), and fasting insulin (-23% vs. +5%; P=0.05). These findings indicate that a modest increase in MVPA can improve metabolic health in sedentary overweight Hispanic adolescents.

  17. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  18. Jogging Therapy for Hikikomori Social Withdrawal and Increased Cerebral Hemodynamics: A Case Report.

    Science.gov (United States)

    Nishida, Masaki; Kikuchi, Senichiro; Fukuda, Kazuhito; Kato, Satoshi

    2016-01-01

    Severe social withdrawal, called hikikomori, has drawn increased public attention. However, an optimal clinical approach and strategy of treatment has not been well established. Here, we report a case of hikikomori for which an exercise intervention using jogging therapy was effective, showing cerebral hemodynamic improvement. The patient was a 20 year old Japanese male who was hospitalized in order to evaluate and treat severe social withdrawal. Although depressive and anxiety symptoms partially subsided with sertraline alone, social withdrawal persisted due to a lack of self confidence. With his consent, we implemented exercise therapy with 30 minutes of jogging three times a week for three months. We did not change the pharmacotherapy, and his social withdrawal remarkably improved with continuous jogging exercise. Using near infrared spectroscopy to evaluate hemodynamic alteration, bilateral temporal hemodynamics considerably increased after the three-month jogging therapy. Regarding exercise therapy for mental illness, numerous studies have reported the effectiveness of exercise therapy for major depression. This case implied, however, that the applicability of exercise therapy is not limited to major depressive disorder. Jogging therapy may contribute to reinforcing self confidence associated with "resilience" in conjunction with neurophysiological modulation of neural networks.

  19. Increases in muscle volume after plantarflexor strength training in children with spastic cerebral palsy.

    Science.gov (United States)

    McNee, Anne E; Gough, Martin; Morrissey, Matt C; Shortland, Adam P

    2009-06-01

    Children with spastic cerebral palsy (CP) have small, weak muscles. However, change in muscle size due to resistance training in this group is unknown. We investigated the effect of plantarflexor strengthening on muscle volume, gait, and function in 13 ambulant children with spastic CP (seven males, six females; mean age 10 y 11 mo, SD 3 y 0 mo, range 6 y 11 mo-16 y 11 mo; eight with diplegia, five with hemiplegia; Gross Motor Function Classification System level I, six; level II, five; level III, two). Assessments were performed before training, 5 and 10 weeks into training, and at a 3-month follow-up. Medial and lateral gastrocnemius volumes were computed from three-dimensional ultrasound images. The number of unilateral heel raises able to be achieved on each side was assessed. Function was measured using three-dimensional gait analysis, the 'timed up and go' test, the Gillette Functional Assessment Questionnaire, and the Functional Mobility Scale. Training involved heel raises or Thera-Band resistance, 4 times a week for 10 weeks. Medial and lateral gastrocnemius volumes increased by 17 and 14% at week 5 (p=0.03, p=0.028). This increase was maintained at week 10 and follow-up (medial gastrocnemius p=0.001, ptraining in children with spastic CP. The role of progressive strength training in maintaining long-term function is discussed.

  20. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    Directory of Open Access Journals (Sweden)

    Hempel Casper

    2008-01-01

    Full Text Available Abstract Background Cerebral malaria (CM is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo has – besides of its well known haematopoietic properties – significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined. Methods Female C57BL/6j mice (4–6 weeks, infected with Plasmodium berghei ANKA, were treated with recombinant human Epo (rhEpo; 50–5000 U/kg/OD, i.p. at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT-mediated deoxyuridine triphosphate (dUTP-digoxigenin nick end labelling, as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR. Results Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect. Conclusion These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.

  1. Does Infection During Pregnancy Outside of the Time of Delivery Increase the Risk of Cerebral Palsy?

    Science.gov (United States)

    Brookfield, Kathleen F; Osmundson, Sarah S; Caughey, Aaron B; Snowden, Jonathan M

    2017-02-01

    Objective We sought to evaluate whether maternal antepartum infection (excluding chorioamnionitis) is associated with cerebral palsy (CP). Study Design This is a secondary analysis from a multicenter trial in women at risk of preterm delivery who received antenatal magnesium sulfate versus placebo. We compared the risk of CP in the children of women who had evidence of antepartum infection over the course of pregnancy to those women who had no evidence of antepartum infection during pregnancy. Results Within a cohort of 2,251 women who met our inclusion criteria, 1,350 women had no history of infection in pregnancy and 801 women had a history of some type of antepartum infection during pregnancy. The incidence of CP was similar between the two groups (4.9 vs 5.0%; p = 0.917). After adjustment for maternal and obstetric confounders, we observed no significantly increased risk of CP among infants born to women with evidence of antepartum infection; (adjusted relative risk [aRR], 1.09 (0.72, 1.66); p = 0.68). Conclusion Compared with women with no evidence of antepartum infection during pregnancy, those women with infections excluding chorioamnionitis may not be at an increased risk of delivering an infant with CP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. The role of the mitochondrial calcium uniporter in cerebral ischemia/reperfusion injury in rats involves regulation of mitochondrial energy metabolism.

    Science.gov (United States)

    Zhao, Qin; Wang, Shilei; Li, Yu; Wang, Peng; Li, Shuhong; Guo, Yunliang; Yao, Ruyong

    2013-04-01

    The mitochondrial calcium uniporter (MCU) maintains intracellular Ca2+ homeostasis by transporting Ca2+ from the cell cytosol into the mitochondrial matrix and is important for shaping Ca2+ signals and the activation of programmed cell death. Inhibition of MCU by ruthenium red (RR) or Ru360 has previously been reported to protect against neuronal death. The aim of the present study was to analyze the mechanisms underlying the effects of MCU activity in a rat model of cerebral ischemia/reperfusion (I/R) injury. Adult male Wistar rats were divided into 4 groups; sham, I/R, I/R + RR and I/R + spermine (Sper) and were subjected to reversible middle cerebral artery occlusion for 2 h followed by 24 h of reperfusion. A bolus injection of RR administered 30 min prior to ischemia was found to significantly decrease the total infarct volume and reduce neuronal damage and cell apoptosis compared with ischemia/reperfusion values. However, treatment with Sper, an activator of the MCU, increased the injury induced by I/R. Analysis of energy metabolism revealed that I/R induced progressive inhibition of complexes I‑IV of the electron transport chain, decreased ATP production, dissipated the mitochondrial membrane potential and increased the generation of reactive oxygen species. Treatment with RR ameliorated the condition, while spermine had the opposite effect. In conclusion, blocking MCU was demonstrated to exert protective effects against I/R injury and this process may be mediated by the prevention of energy failure.

  3. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    Science.gov (United States)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  4. Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Gispert, Juan D; Reig, Santiago; Pascau, Javier; Martínez, Raúl; Sanz, Javier; Palomo, Tomás; Desco, Manuel

    2005-01-01

    The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

  5. Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of cerebral malaria.

    Science.gov (United States)

    Campos, A C; Brant, F; Miranda, A S; Machado, F S; Teixeira, A L

    2015-03-19

    Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection that might cause permanent neurological deficits. Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties. In the present work, we evaluated the effects of CBD in a murine model of CM. Female mice were infected with Plasmodium berghei ANKA (PbA) and treated with CBD (30mg/kg/day - 3 or 7days i.p.) or vehicle. On 5th day-post-infection (dpi), at the peak of the disease), animals were treated with single or repeated doses of Artesunate, an antimalarial drug. All groups were tested for memory impairment (Novel Object Recognition or Morris Water Maze) and anxiety-like behaviors (Open field or elevated plus maze test) in different stages of the disease (at the peak or after the complete clearance of the disease). Th1/Th2 cytokines and neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) were measured in the prefrontal cortex and hippocampus of experimental groups. PbA-infected mice displayed memory deficits and exhibited increase in anxiety-like behaviors on the 5dpi or after the clearance of the parasitemia, effects prevented by CBD treatment. On 5dpi, TNF-α and IL-6 increased in the hippocampus, while only IL-6 increased in the prefrontal cortex. CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6). Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.

  6. Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats.

    Science.gov (United States)

    Suge, Rie; Shimazu, Tomokazu; Hasegawa, Hajime; Inoue, Ikuo; Hayashibe, Hidemasa; Nagasaka, Hironori; Araki, Nobuo; Katayama, Shigehiro; Nomura, Masahiko; Watanabe, Shu-Ichi

    2012-10-24

    In this study, we examined alterations in the enzymatic antioxidant defenses associated with learning deficits induced by type 2 diabetes, and studied the effects of the peroxisome proliferator-activated receptor γ agonist pioglitazone on these learning deficits. Learning ability was assessed by visual discrimination tasks in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of spontaneous type 2 diabetes. Levels of the antioxidant enzymes glutathione peroxidase (GPx), Cu(2+)-Zn(2+) superoxide dismutase (CuZn-SOD) and manganese SOD were measured in the cortex, hippocampus and striatum. Half the rats received oral pioglitazone (20mg/kg/day) from the early stage of diabetes (22 weeks old) to 27 weeks old. OLETF rats showed learning deficits compared with control, Long-Evans Tokushima Otsuka (LETO) rats. GPx levels in the cortex and hippocampus were increased in OLETF rats compared with LETO rats, with an inverse correlation between GPx in the hippocampus and learning score. CuZn-SOD levels were also increased in the hippocampus in OLETF rats. Pioglitazone reduced blood glucose and increased serum adiponectin levels, but had no effect on learning tasks or antioxidant enzymes, except for CuZn-SOD. These results suggest that an oxidative imbalance reflected by increased brain antioxidant enzymes plays an important role in the development of learning deficits in type 2 diabetes. Early pioglitazone administration partly ameliorated diabetic symptoms, but was unable to completely recover cerebral oxidative imbalance and functions. These results suggest that diabetes-induced brain impairment, which results in learning deficits, may have occurred before the appearance of the symptoms of overt diabetes.

  7. Effects of dopamine infusion on cerebral blood flow, brain cell membrane function and energy metabolism in experimental Escherichia coli meningitis in the newborn piglet.

    OpenAIRE

    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

    In the present study, we tested whether maintenance of adequate cerebral perfusion pressure (CPP) by pharmacologically preventing systemic hypotension with dopamine infusion would prevent cerebral ischemia and attenuate energy depletion and neuronal injury even though intracranial pressure remains elevated in a newborn piglet meningitis model. Cerebral blood flow, measured at the end of the experiment using fluorescent microspheres, was significantly increased by dopamine infusion. The decrea...

  8. Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Wiseman, Stewart J; Bastin, Mark E; Jardine, Charlotte L; Barclay, Gayle; Hamilton, Iona F; Sandeman, Elaine; Hunt, David; Amft, E Nicole; Thomson, Susan; Belch, Jill F F; Ralston, Stuart H; Wardlaw, Joanna M

    2016-11-01

    Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; PSVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications. © 2016 The Authors.

  9. Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

    Directory of Open Access Journals (Sweden)

    Geissy LL Araújo

    2014-03-01

    Full Text Available The morphogen Sonic Hedgehog (SHH plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

  10. Over hydration in diabetic ketoacidosis may increase the risk of cerebral edema in children

    Institute of Scientific and Technical Information of China (English)

    Zakaullh Khan; Dulikun Muzhapaer

    2013-01-01

    Objectives Over-hydration in diabetic ketoacidosis (DKA) may increase the risk of cerebral edema in children. Methods We have organized a prospective descriptive cohort study of 38 pediatric patients aged 1 month to 14 years, who were diagnosed with DKA with 41 episodes of diabetic ketoacidosis, presented to the pediatric emergency department at the First Affiliated Hospital of Xinjiang Medical University from January 2010 to February 2012.This study was approved by the Ethics Committee of The First Affiliated Hospital of Xinjiang Medical University. Results The magnitude presentation of the percentile 25%-70% was in the ratio of 5.6% (3.4%-8.2%) (6.1±4) .So there was no clinical and biochemical assessment variation needed. These both of the variations, all of the diabetic ketoacidosis patient approached. Further all the patient variations were not correlated with the amplitude of variation and magnitude presentation and did not affect the fluid concentration and the quantity of the fluid was 47.8 mL/kg (36.5-56.3) in the first 12 hours. Conclusion For the conclusion of the exact parameters and the magnitude variations of the fluid in the patients of diabetic ketoacidosis, all of the conformations need study on the larger scale.

  11. Intensive blood pressure lowering increases cerebral blood flow in older subjects with hypertension.

    Science.gov (United States)

    Tryambake, Dinesh; He, Jiabao; Firbank, Michael J; O'Brien, John T; Blamire, Andrew M; Ford, Gary A

    2013-06-01

    Hypertension is associated with reduced cerebral blood flow (CBF). Intensive (blood pressure (BP) lowering in older people might give greater reduction in cardiovascular risk, but there are concerns that this might produce hypoperfusion which may precipitate falls and possibly stroke. We determined the effect of intensive compared with usual BP lowering on CBF in hypertensive older subjects. Individuals aged >70 years with a history of systolic hypertension on 1 or no BP lowering drugs were recruited from primary care (n=37; age, 75±4 years; systolic BP, >150 mm Hg) and randomized to receive intensive (target BP, treatment. Baseline BP (ambulatory or in clinic) and baseline gray matter CBF were not significantly different between the groups. After treatment, BP was reduced significantly in both groups but fell more in the intensive group (26/17 versus 15/5 mm Hg; Phypertension increases CBF, compared with BP lowering to usual target. These findings suggest hypertension in older people shifts the autoregulatory CBF curve rightward and downward and is reversible with BP lowering.

  12. Unique discrepancy between cerebral blood flow and glucose metabolism in hemimegalencephaly.

    Science.gov (United States)

    Uematsu, Mitsugu; Haginoya, Kazuhiro; Togashi, Noriko; Hino-Fukuyo, Naomi; Nakayama, Tojo; Kikuchi, Atsuo; Abe, Yu; Wakusawa, Keisuke; Matsumoto, Yoko; Kakisaka, Yosuke; Kobayashi, Tomoko; Hirose, Mieko; Yokoyama, Hiroyuki; Iinuma, Kazuie; Iwasaki, Masaki; Nakasato, Nobukazu; Kaneta, Tomohiro; Akasaka, Manami; Kamei, Atsushi; Tsuchiya, Shigeru

    2010-12-01

    Hemimegalencephaly (HME) presents as severe refractory seizures and requires early surgical treatment to prevent progression to catastrophic epilepsy. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are useful imaging techniques for the presurgical evaluation of patients with intractable epilepsy. However, the results in HME are variable and no study has compared SPECT and PET performed at around the same time. We performed SPECT and PET for nine patients with HME, which was defined as a whole or part of affected hemisphere enlargement (three males, six females; age range 0.5-20 years). The ictal and interictal states were determined based on the presence or absence of clinical seizures during all PET examinations and majority of SPECT examinations. The perfusion pattern in the malformed hemisphere was increased or equal, despite the reduced glucose metabolism in six out of nine patients. Five of the six patients who underwent early surgical treatment showed this kind of perfusion/metabolism discrepancy. Importantly, even the non-affected hemisphere in early infantile cases already lacked the normal hypoperfusion and hypometabolism patterns of immature frontal lobes, which was most prominent in case with poor surgical prognosis. In all six surgical patients, epileptic seizures appeared before 4 months of age. By contrast, none of the non-surgical patients had seizures before 4 months of age. In conclusion, although the number of patients examined is small and the result is still preliminary, the perfusion/metabolism discrepancy found in this study may show potential characteristic aspect of HME and further study with simultaneous EEG recording will make clear if this finding can be useful indicator for early surgical treatment in HME. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. 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

    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....... RESULTS: The included patients had a mean GCS of 8 (range, 3-10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although...

  14. Electroacupuncture-attenuated ischemic brain injury increases insulin-like growth factor-1expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Ling Wang; Yunliang Guo

    2010-01-01

    Acupuncture has recently gained popularity in many countries as an alternative and complementary therapeutic intervention.Previous studies have shown that changes in genes,proteins,and their metabolites were measureable during acupuncture for treatment of cerebral ischemia.Through the use of in situ hybridization and immunohistochemistry,the present study confirmed that electroacupuncture increased insulin-like growth factor-1 mRNA and protein expression in the corpus striatum following cerebral ischemia,reduced brain edema following middle cerebral artery occlusion repeffusion,and decreased infarct volume.Results suggested that electroacupuncture is effective in the relief of cerebral ischemia by increasing endogenous insulin-like growth factor-1 expression.

  15. Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia.

    Science.gov (United States)

    Choi, Hyun Young; Park, Joon Ha; Chen, Bai Hui; Shin, Bich Na; Lee, Yun Lyul; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Yan, Bing Chun; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Kim, Sung Koo

    2016-09-01

    Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin-eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment.

  16. Cerebral white matter blood flow and energy metabolism in multiple sclerosis

    NARCIS (Netherlands)

    Steen, Christel; D'haeseleer, Miguel; Hoogduin, Johannes M.; Fierens, Yves; Cambron, Melissa; Mostert, Jop P.; Heersema, Dorothea J.; Koch, Marcus W.; De Keyser, Jacques

    2013-01-01

    Background: Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. Objective: The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial me

  17. BH4 treatment in BH4-responsive PKU patients: preliminary data on blood prolactin concentrations suggest increased cerebral dopamine concentrations.

    Science.gov (United States)

    van Vliet, Danique; Anjema, Karen; Jahja, Rianne; de Groot, Martijn J; Liemburg, Geertje B; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; Derks, Terry G J; Kema, Ido P; van Spronsen, Francjan J

    2015-01-01

    In phenylketonuria (PKU), cerebral neurotransmitter deficiencies have been suggested to contribute to brain dysfunction. Present treatment aims to reduce blood phenylalanine concentrations by a phenylalanine-restricted diet, while in some patients blood phenylalanine concentrations also respond to cofactor treatment with tetrahydrobiopterin (BH4). Recently, a repurposing approach of BH4 was suggested to increase cerebral neurotransmitter synthesis. To investigate whether BH4 may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, we investigated blood prolactin concentrations-as a parameter of brain dopamine availability. We retrospectively compared blood prolactin in relation to blood phenylalanine concentrations of nine (male) BH4-responsive PKU patients, when being treated without and with BH4. Blood prolactin concentrations positively correlated to blood phenylalanine concentrations (p=0.002), being significantly lower with than without BH4 treatment (p=0.047). In addition, even in this small number of male patients, blood prolactin concentrations tended to be lower at increasing BH4 dose (p=0.054), while taking blood phenylalanine concentrations into account (p=0.002). In individual BH4-responsive patients, median blood prolactin concentrations were significantly lower while using BH4 than before using BH4 treatment (p=0.024), whereas median blood phenylalanine concentrations tended to be lower, but this did not reach statistical significance (p=0.107). Therefore, these data show that high blood phenylalanine in BH4-responsive PKU male patients seems to be associated with increased blood prolactin concentrations, suggesting reduced cerebral dopamine availability. Moreover, these data suggest that BH4 treatment in itself could decrease blood prolactin concentrations in a dose-responsive way, independent of blood phenylalanine concentrations. We conclude that these preliminary data

  18. Molecular mechanisms of increased cerebral vulnerability after repeated mild blast-induced traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Alaa Kamnaksh

    2014-06-01

    Full Text Available The consequences of a mild traumatic brain injury can be especially severe if it is repeated within the period of increased cerebral vulnerability (ICV that follows the initial insult. To better understand the molecular mechanisms that contribute to ICV, we exposed rats to different levels of mild blast overpressure (5 exposures; total pressure range: 15.54–19.41 psi or 107.14–133.83 kPa at a rate of 1 per 30 min, monitored select physiological parameters, and assessed behavior. Two days post-injury or sham, we determined changes in protein biomarkers related to various pathologies in behaviorally relevant brain regions and in plasma. We found that oxygen saturation and heart rate were transiently depressed following mild blast exposure and that injured rats exhibited significantly increased anxiety- and depression-related behaviors. Proteomic analyses of the selected brain regions showed evidence of substantial oxidative stress and vascular changes, altered cell adhesion, and inflammation predominantly in the prefrontal cortex. Importantly, these pathological changes as well as indications of neuronal and glial cell loss/damage were also detected in the plasma of injured rats. Our findings illustrate some of the complex molecular changes that contribute to the period of ICV in repeated mild blast-induced traumatic brain injury. Further studies are needed to determine the functional and temporal relationship between the various pathomechanisms. The validation of these and other markers can help to diagnose individuals with ICV using a minimally invasive procedure and to develop evidence-based treatments for chronic neuropsychiatric conditions.

  19. 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

  20. Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation.

    Science.gov (United States)

    Ances, Beau M; Liang, Christine L; Leontiev, Oleg; Perthen, Joanna E; Fleisher, Adam S; Lansing, Amy E; Buxton, Richard B

    2009-04-01

    Calibrated functional magnetic resonance imaging (fMRI) provides a noninvasive technique to assess functional metabolic changes associated with normal aging. We simultaneously measured both the magnitude of the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) responses in the visual cortex for separate conditions of mild hypercapnia (5% CO(2)) and a simple checkerboard stimulus in healthy younger (n = 10, mean: 28-years-old) and older (n = 10, mean: 53-years-old) adults. From these data we derived baseline CBF, the BOLD scaling parameter M, the fractional change in the cerebral metabolic rate of oxygen consumption (CMRO(2)) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO(2). For the functional activation paradigm, the magnitude of the BOLD response was significantly lower for the older group (0.57 +/- 0.07%) compared to the younger group (0.95 +/- 0.14%), despite the finding that the fractional CBF and CMRO(2) changes were similar for both groups. The weaker BOLD response for the older group was due to a reduction in the parameter M, which was significantly lower for older (4.6 +/- 0.4%) than younger subjects (6.5 +/- 0.8%), most likely reflecting a reduction in baseline CBF for older (41.7 +/- 4.8 mL/100 mL/min) compared to younger (59.6 +/- 9.1 mL/100 mL/min) subjects. In addition to these primary responses, for both groups the BOLD response exhibited a post-stimulus undershoot with no significant difference in this magnitude. However, the post-undershoot period of the CBF response was significantly greater for older compared to younger subjects. We conclude that when comparing two populations, the BOLD response can provide misleading reflections of underlying physiological changes. A calibrated approach provides a more quantitative reflection of underlying metabolic changes than the BOLD response alone.

  1. Increased prevalence of antibodies against dietary proteins in children and young adults with cerebral palsy.

    Science.gov (United States)

    Stenberg, Reidun; Dahle, Charlotte; Magnuson, Anders; Hellberg, Dan; Tysk, Curt

    2013-02-01

    Undernourishment is common in children with cerebral palsy (CP), but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE antibodies against wheat and gluten. Sera from 99 cases with CP and 99 healthy, age- and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay for detection of IgG antibodies against β-lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG, and IgE antibodies against gluten and wheat. Compared with controls, the odds ratio in cases with CP for having elevated levels of IgG antibodies against β-lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein 11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP subtypes had significantly higher frequencies of elevated levels for all of the tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly lower weight was seen in cases with CP with positive versus negative serology. Elevated levels of IgG against dietary antigens were more frequent in the CP group compared with controls, and particularly in the tetraplegic and dyskinetic CP subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.

  2. Interregional cerebral metabolic associativity during a continuous performance task (Part II) : differential alterations in bipolar and unipolar disorders.

    Science.gov (United States)

    Benson, Brenda E; Willis, Mark W; Ketter, Terence A; Speer, Andrew; Kimbrell, Tim A; George, Mark S; Herscovitch, Peter; Post, Robert M

    2008-10-30

    Unipolar and bipolar disorders have often been reported to exhibit abnormal regional brain activity in prefrontal cortex and paralimbic structures compared with healthy controls. We sought to ascertain how regions postulated to be abnormal in bipolar and unipolar disorders were functionally connected to the rest of the brain, and how this associativity differed from healthy controls. Thirty patients with bipolar disorder (BPs), 34 patients with unipolar disorder (UPs), and 66 healthy volunteers (Willis, M.W., Benson, B.E., Ketter, T.A., Kimbrell, T.A., George, M.S., Speer, A.M., Herscovitch, P., Post, R.M., 2008. Interregional cerebral metabolic associativity during a continuous performance task in healthy adults. Psychiatry Research: Neuroimaging 164 (1)) were imaged using F-18-fluorodeoxyglucose and positron emission tomography (FDG-PET) while performing an auditory continuous performance task (CPT). Five bilateral regions of interest (ROIs), namely dorsolateral prefrontal cortex (DLPFC), insula, inferior parietal cortex (INFP), thalamus and cerebellum, were correlated with normalized cerebral metabolism in the rest of the brain while covarying out Hamilton Depression Rating Scale Scores. In bipolar patients compared with controls, metabolism in the left DLPFC and INFP, and bilateral thalamus and insula had more positive and fewer negative metabolic correlations with other brain regions. In contrast, compared with controls, unipolar patients had fewer significant correlative relationships, either positive or negative. In common, bipolar and unipolar patients lacked the normal inverse relationships between the DLPFC and cerebellum, as well as relationships between the primary ROIs and other limbic regions (medial prefrontal cortex, anterior cingulate, and temporal lobes) compared with controls. Associations of DLPFC and INFP with other brain areas were different in each hemisphere in patients and controls. Bipolar patients exhibited exaggerated positive coherence

  3. Focal increase of blood flow in the cerebral cortex of man during vestibular stimulation

    DEFF Research Database (Denmark)

    Friberg, L; Olsen, T S; Roland, P E

    1985-01-01

    This study is an attempt to reveal projection areas for vestibular afferents to the human brain. Changes in regional cerebral blood flow (rCBF) were measured over 254 cortical regions during caloric vestibular stimulation with warm water (44 degrees C). rCBF was measured when the external auditor...... stimulation that gives rise to the associated conscious vestibular sensation of vertigo....

  4. Middle cerebral artery occlusion in presence of low perfusion pressure increases infarct size in rats

    DEFF Research Database (Denmark)

    Sillesen, H; Nedergaard, Majken; Schroeder, T;

    1988-01-01

    A model was set up in order to evaluate the importance of hemispheric perfusion pressure when the middle cerebral artery (MCA) is occluded in anaesthetized rats. In 6 animals the internal carotid artery (ICA) was occluded prior to ipsilateral MCA occlusion; in 17 animals the MCA only was occluded...

  5. Cerebral palsy in eastern Denmark: declining birth prevalence but increasing numbers of unilateral cerebral palsy in birth year period 1986-1998.

    Science.gov (United States)

    Ravn, Susanne Holst; Flachs, Esben Meulengracht; Uldall, Peter

    2010-05-01

    The Cerebral Palsy Registry in eastern Denmark has been collecting cases using a uniform data sampling procedure since birth year 1979. Children are included by two child neurologists and an obstetrician. Information on pregnancy, birth, neonatal period, impairments and demographic data are registered. The total cerebral palsy birth prevalence has been significantly decreasing since the birth period 1983-1986 with 3.0 per 1000 live births until the period 1995-1998 with 2.1 per 1000 live births. The overall decrease was seen in preterm infants (term infants and despite a simultaneous fall in perinatal and early neonatal mortality in the preterm group. Analysing the subtypes of CP we found a significant increase in the numbers as well as the rate of unilateral CP with a simultaneous fall in the numbers as well as the rate of bilateral CP. The explanation of this rise is not obvious. A change from bilateral periventricular lesions to unilateral is a possibility, but no major change in the neonatal handling could be documented. Regarding associated impairments, developmental delay/learning disabilities as well as motor function assessed by ability to walk (unassisted/assisted), both have changed toward higher percentage of children with unassisted walking and in need of special education.

  6. 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

    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......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...... 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...

  7. Increase in physical activities in kindergarten children with cerebral palsy by employing MaKey-MaKey-based task systems.

    Science.gov (United States)

    Lin, Chien-Yu; Chang, Yu-Ming

    2014-09-01

    In this study, we employed Flash- and Scratch-based multimedia by using a MaKey-MaKey-based task system to increase the motivation level of children with cerebral palsy to perform physical activities. MaKey MaKey is a circuit board that converts physical touch to a digital signal, which is interpreted by a computer as a keyboard message. In this study, we used conductive materials to control this interaction. This study followed single-case design using ABAB models in which A indicated the baseline and B indicated the intervention. The experiment period comprised 1 month and a half. The experimental results demonstrated that in the case of two kindergarten children with cerebral palsy, their scores were considerably increased during the intervention phrases. The developmental applications of the results are also discussed.

  8. Subanesthetic concentration of sevoflurane increases regional cerebral blood flow more, but regional cerebral blood volume less, than subanesthetic concentration of isoflurane in human volunteers.

    Science.gov (United States)

    Lorenz, I H; Kolbitsch, C; Hörmann, C; Schocke, M; Felber, S; Zschiegner, F; Hinteregger, M; Kremser, C; Pfeiffer, K P; Benzer, A

    2001-10-01

    Both sevoflurane and isoflurane are used in moderate concentrations in neuroanesthesia practice. The limiting factors for using higher concentrations of inhalational anesthetics in patients undergoing neurosurgery are the agents' effects on cerebral blood flow (CBF) and cerebral blood volume (CBV). In particular, an increase in CBV, which is a key determinant of intracranial pressure, may add to the neurosurgical patient's perioperative risk. To compare the effects of a subanesthetic concentration (0.4 minimum alveolar concentration) of sevoflurane or isoflurane on regional CBF (rCBF), regional CBV (rCBV) and regional mean transit time (rMTT), contrast-enhanced magnetic resonance imaging perfusion measurements were made in spontaneously breathing human volunteers. Absolute changes in rCBF, regional CBV, and rMTT during administration of either drug in regions of interest outlined bilaterally in white and grey matter were nonparametrically (Mann-Whitney test) analyzed. Sevoflurane increased rCBF in practically all regions (absolute change, 4.44 +/- 2.87 to 61.54 +/- 2.39 mL/100g per minute) more than isoflurane did (absolute change, 12.91 +/- 2.52 to 52.67 +/- 3.32 mL/100g per minute), which decreased frontal, parietal, and white matter rCBF (absolute change, -1.12 +/- 0.59 to -14.69 +/- 3.03 mL/100g per minute). Regional CBV was higher in most regions during isoflurane administration (absolute change, 0.75 +/- 0.03 to 4.92 +/- 0.16 mL/100g) than during sevoflurane administration (absolute change, 0.05 +/- 0.14 to 3.57 +/- 0.14 mL/100g). Regional mean transit time was decreased by sevoflurane (absolute change, -0.18 +/- 0.05 to -0.60 +/- 0.04 s) but increased by isoflurane (absolute change, 0.19 +/- 0.03 to 0.69 +/- 0.04 s). In summary, regional CBV was significantly lower during sevoflurane than during isoflurane administration, although sevoflurane increased rCBF more than isoflurane, which even decreased rCBF in some regions. For sevoflurane and, even more

  9. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

    Science.gov (United States)

    Leke, Renata; Bak, Lasse K; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-04-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

  10. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  11. The role of depressed metabolism in increased radio-resistance

    Science.gov (United States)

    Musacchia, X. J.

    1975-01-01

    The results of experiments on hamsters and rats to determine physiological responses to various temperature conditions are presented. The experimental methods described are considered to be applicable to future mammalian experiments in space. Renal function was examined in the golden hamster as a function of body temperature. Hamsters were also acclimated to heat and metabolic rates, body temperature, skin temperature, cardiac distribution and whole body hematocrits were measured. In addition, the effects of heat stress on the intestinal transport of sugars in the hamster and rat were studied. The biological effects of prolonged space flight and methods of simulating weightlessness are also discussed.

  12. Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

    Institute of Scientific and Technical Information of China (English)

    Jinnan Zhang; Wei Lu; Qiang Lei; Xi Tao; Hong You; Pinghui Xie

    2013-01-01

    Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

  13. Differential increases in blood flow velocity in the middle cerebral artery after tourniquet deflation during sevoflurane, isoflurane or propofol anaesthesia.

    Science.gov (United States)

    Kadoi, Y; Kawauchi, C H; Ide, M; Saito, S; Mizutani, A

    2009-07-01

    The purpose of this study was to examine the comparative effects of sevoflurane, isoflurane or propofol on cerebral blood flow velocity after tourniquet deflation during orthopaedic surgery. Thirty patients undergoing elective orthopaedic surgery were randomly divided into sevoflurane, isoflurane and propofol groups. Anaesthesia was maintained with sevoflurane, isoflurane or propofol infusion in 33% oxygen and 67% nitrous oxide, in whatever concentrations were necessary to keep bispectral index values between 45 and 50. Ventilatory rate or tidal volume was adjusted to target PaCO2 of 35 mmHg. A 2.0 MHz transcranial Doppler probe was attached to the patient's head at the temporal window and mean blood flow velocity in the middle cerebral artery was continuously measured. The extremity was exsanguinated with an Esmarch bandage and the pneumatic tourniquet was inflated to a pressure of 450 mmHg. Arterial blood pressure, heart rate, velocity in the middle cerebral artery and arterial blood gas analysis were measured every minute for 10 minutes after release of the tourniquet in all three groups. Velocity in the middle cerebral artery in the three groups increased for five minutes after tourniquet deflation. Because of the different cerebrovascular effects of the three agents, the degree of increase in flow velocity in the isoflurane group was greater than in the other two groups, the change in flow velocity in the propofol group being the lowest (at three minutes after deflation 40 +/- 7%, 32 +/- 6% and 28 +/- 10% in the isoflurane, sevoflurane and propofol groups respectively, P < 0.05).

  14. Cerebral carbohydrate cost of physical exertion in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ogoh, Shigehiko; Dawson, Ellen A

    2004-01-01

    Above a certain level of cerebral activation the brain increases its uptake of glucose more than that of O(2), i.e., the cerebral metabolic ratio of O(2)/(glucose + 12 lactate) decreases. This study quantified such surplus brain uptake of carbohydrate relative to O(2) in eight healthy males who p...

  15. Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka [Nagoya City Rehabilitation and Sports Center (Japan)

    2002-06-01

    Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with {sup 15}O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO{sub 2} in all regions. Then we compared rCBF, OEF, and CMRO{sub 2} between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO{sub 2} along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO{sub 2} of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO{sub 2} between normal group and impaired group revealed that CMRO{sub 2} of the impaired group was significantly lower than that of the

  16. The significance of changes in cerebral oxygen and glucose metabolism in patients with cerebral hemorrhage caused by acute hypertension%急性高血压脑出血患者脑糖氧代谢变化及意义

    Institute of Scientific and Technical Information of China (English)

    马骏; 陈锷峰; 屠传建; 钱辉; 骆明; 顾志伟; 张建民

    2014-01-01

    find the relationship between levels of those biomarkers and outcomes of patients.Thereafter,the results of this retrospective study inspired us to carry out a prospective and double blind study in another 23 patients from July 2012 to January 2013 for further confirming the validity of these biomarkers to predict the short-term outcomes of patients.The statistical analysis was performed with SPSS 16.0 software (SPSS,USA) and a P < 0.05 was considered significant.Numerical values were given as means ± SD unless stated otherwise.For statistical analyses,normality was assessed before choosing the relevant comparative test and nonparametric tests was used in cases as the normality test failed.Results Of 43 patients with cerebral hemorrhage for retrospective analysis,there were 27 male and 16 female with M/F ratio =1.7:1,aged from 49 to 81 with mean 66.2 ± 15.3 years and their GCS scores were 5-8.of them,there were 28 patients suffered from basal ganglia hemorrhage,6 cerebella hemorrhage,5 pons cerebelli hemorrhage and 4 lobe hemorrhage.There were 25 patients with supratentorial hematoma in volume of no less than 30 mL and 10 infratentorial hematoma in volume of no less than 10 mL of them,11 patients were treated with craniotomy and evacuation of hematoma or decompression craniotomy and rest were treated with conservative strategy.Compared with the death group,the CEO2,AVDO2,V-AGlu,V-ALac in the survival group decreased significantly (P < 0.05),while V-APCO2 and SjvO2 increased significantly (P < 0.05).In the subsequent prospective study,the accuracy rate of the levels of SjvO2 < 52%,AVDO2 > 83% for predicting prognosis was 78.3%.Conclusions The cerebral oxygen and glucose metabolism was obviously abnormal in hypertensive cerebral hemorrhagic patients with GCS score of 5-8 among the death group,and especially the anaerobic metabolism was apparently increased.It was also found that the risk threshold (SjvO2 < 52%,AVDO2 >83%) was in close

  17. Metabolic and neurological patterns in chronic cerebral infarction: a single-voxel {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Kamada, K. [Department of Neurosurgery, Hokkaido University School of Medicine, North-15, West-7, Kita-Ku, Sapporo 060 (Japan); Houkin, K. [Department of Neurosurgery, Hokkaido University School of Medicine, North-15, West-7, Kita-Ku, Sapporo 060 (Japan); Iwasaki, Y. [Department of Neurosurgery, Hokkaido University School of Medicine, North-15, West-7, Kita-Ku, Sapporo 060 (Japan); Abe, H. [Department of Neurosurgery, Hokkaido University School of Medicine, North-15, West-7, Kita-Ku, Sapporo 060 (Japan); Kashiwaba, T. [Kashiwaba Neurosurgical Hospital, Hokkaido (Japan)

    1997-08-01

    The details of brain metabolism in chronic cerebral infarcts have not been clarified. Using proton MR spectroscopy ({sup 1}H-MRS) at 1.5 T, we measured biochemical changes in 16 patients with large infarcts involving the motor cortex in the chronic phase (median 293.9 days) and related the findings to clinical data. Localised spectra were obtained using point-resolved spectroscopy, with an echo time of 270 ms. Regions of interest were placed on the frontal lobe, including the precentral gyrus and central sulcus. Motor function was assessed by the manual muscle power test at the time of the {sup 1}H-MRS study. Only three patients with severe paresis had no signal in the lesions and a lactate signal was obtained in 13 cases. N -acetyl aspartate (NAA) was observed in 4 cases with recanalisation of an occluded vessel. Motor function correlated strongly with the NAA/choline-containing compounds (Cho) ratio (P < 0.01) and lactate/Cho ratio (P < 0.01). We found various metabolic patterns, reflecting residual neurological function. (orig.). With 4 figs., 2 tabs.

  18. The effect of diazepam sedation on cerebral glucose metabolism in Alzheimer's disease as measured using positron emission tomography.

    Science.gov (United States)

    Foster, N L; VanDerSpek, A F; Aldrich, M S; Berent, S; Hichwa, R H; Sackellares, J C; Gilman, S; Agranoff, B W

    1987-08-01

    The effect of sedation induced by intravenous diazepam on cerebral glucose metabolic activity was examined with [18F]2-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in five patients with probable Alzheimer's disease. Each subject was studied on 2 separate days: on one occasion at rest with eyes patched and ears open, and on the second when sedated with intravenous diazepam titrated to maintain stage II sleep by clinical and EEG criteria. Similar patterns of glucose uptake were observed in both the presence and the absence of sedation, but overall glucose utilization was depressed an average of 20% and was closely correlated with the amount of diazepam administered prior to the injection of FDG. The predominant temporoparietal hypometabolism and relative sparing of frontal metabolism observed in this disease are therefore not explained by differences in anxiety or activity level in this patient group. Utilization of diazepam sedation for PET study appears to be safe and may permit the study of patients otherwise unable to cooperate with FDG-PET procedures.

  19. Nitric oxide does not act as a mediator coupling cerebral blood flow to neural activity following somatosensory stimuli in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Kjaer, T; Jørgensen, M B;

    1993-01-01

    The possible role of nitric oxide (NO) on vibrissa-stimulated increase of regional cerebral cerebral blood flow (rCBF) and cerebral metabolic rate of glucose (rCMRglu) was investigated in conscious Wistar rats by using an inhibitor of NO synthase, NG-nitro-L-arginine (NOLAG) at a concentration of...

  20. Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8.

    Directory of Open Access Journals (Sweden)

    Tiago B Rodrigues

    Full Text Available Mutations of the monocarboxylate transporter 8 (MCT8 cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3 transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13C glucose and brain extracts prepared and analyzed by (13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

  1. Treatment with dehydroepiandrosterone increases peripheral benzodiazepine receptors of mitochondria from cerebral cortex in D-galactose-induced aged rats.

    Science.gov (United States)

    Chen, Chunfu; Lang, Senyang; Zuo, Pingping; Yang, Nan; Wang, Xiangqing

    2008-12-01

    The aim of this study was to determine whether dehydroepiandrosterone (DHEA) could regulate the expression of peripheral benzodiazepine receptors of mitochondria in cerebral cortex. The rats were divided into five groups. Those, in the vehicle-physiological or senescent group, received physiological or d-galactose (subcutaneously) once a day. Rats, in the vehicle-dimethyl sulfoxide- or DHEA-treated senescent group, received 2% of dimethyl sulfoxide or DHEA (intraperitoneally) every other day besides D-galactose (subcutaneously) once a day. Rats in the DHEA-treated normal group received physiological once a day and DHEA every other day. After 8-week, spatial learning was assessed for 5 days by water maze methods. Following behavioural testing, the cerebral cortex mitochondria were purified for PK11195 binding analysis. When compared to the respective vehicle, D-galactose alone induced a significant impairment in water maze performance accompanied by a reduction (30.7%) in peripheral benzodiazepine receptor density of mitochondria, and DHEA displayed a significant enhancement in learning memory accompanied by the elevation (18.3%) of peripheral benzodiazepine receptor density but not affinity in senescent rats. DHEA showed insignificant effects on both learning/memory ability and peripheral benzodiazepine receptors in normal rats when compared to physiological saline. These results suggest that chronic treatment with DHEA enhance cognitive function and increase peripheral benzodiazepine receptor density in cerebral cortex mitochondria in middle-aged senescent rats.

  2. Excess salt increases infarct size produced by photothrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Hiroshi Yao

    Full Text Available Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline or water, spontaneously hypertensive rats (SHR and normotensive Wistar-Kyoto rats (WKY were subjected to photothrombotic middle cerebral artery occlusion (MCAO, and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning, was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p = 0.002, while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats.

  3. Clinical Factors Associated with Cerebral Metabolism in Term Neonates with Congenital Heart Disease.

    Science.gov (United States)

    Harbison, Anna Lonyai; Votava-Smith, Jodie K; Del Castillo, Sylvia; Kumar, S Ram; Lee, Vince; Schmithorst, Vincent; Lai, Hollie A; O'Neil, Sharon; Bluml, Stefan; Paquette, Lisa; Panigrahy, Ashok

    2017-04-01

    To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy. Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids). Multivariable regression was performed to search for associations between (1) patient-specific/prenatal/preoperative factors with concurrent brain metabolism and (2) intraoperative and postoperative factors with postoperative brain metabolism. A total of 83 magnetic resonance images were obtained on 55 subjects. No patient-specific, prenatal, or preoperative factors associated with concurrent metabolic brain dysmaturation or elevated lactate could be identified. Chromosome 22q11 microdeletion and age at surgery were predictive of altered concurrent white matter phosphocreatine (P term infants with CHD, but not patient-specific, preoperative, or intraoperative factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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.

  5. Lean adolescents with increased risk for metabolic syndrome.

    Science.gov (United States)

    Molero-Conejo, Emperatriz; Morales, Luz Marina; Fernández, Virginia; Raleigh, Xiomara; Gómez, Maria Esther; Semprún-Fereira, Maritza; Campos, Gilberto; Ryder, Elena

    2003-03-01

    The aim of the present study was to determine in adolescents the relationship between insulin levels and body mass index (BMI), body fat distribution, diet, life style and lipid profile. We studied 167 adolescents (68 boys and 99 girls) whose ages ranged from 14 to 17 years. A detailed medical (including pubertal stage) and nutritional record was obtained from each subject. Biochemical measurements included fasting serum insulin, glucose, total cholesterol (TC), triglycerides (Tg), HDL-C, LDL-C and VLDL-C. HOMA insulin resistance (IR) and HOMA beta-cell function (beta-cell) were calculated. Insulin levels were over 84 pmol/L (cut off normal value in our lab) in 56% of the boys and 43% of the girls. Thirty-seven percent of lean adolescents whose BMI was 21.5 +/- 1.9 kg/m2 presented higher fasting insulin levels. HOMA IR, Tg, systolic (SBP) and diastolic blood pressure (DBP) values when compared to a lean normoinsulinemic group. Insulin levels were correlated (p 24 kg/m2) had significantly higher serum insulin, HOMA beta-cell, and Tg levels, and the lowest HDL-C levels. A high-energy intake rich in saturated fat and low physical activity were found in this lean but metabolically altered adolescents. We conclude that even with a BMI as low as 21 kg/m2 an inappropriate diet and low physical activity might be responsible for the high insulin levels and dislipidemias in adolescents.

  6. Staphylococcus aureus redirects central metabolism to increase iron availability.

    Directory of Open Access Journals (Sweden)

    David B Friedman

    2006-08-01

    Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

  7. Staphylococcus aureus redirects central metabolism to increase iron availability.

    Directory of Open Access Journals (Sweden)

    David B Friedman

    2006-08-01

    Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

  8. 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.)

  9. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.

    Directory of Open Access Journals (Sweden)

    Eleanor C Saunders

    2014-01-01

    Full Text Available Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13C-stable isotope resolved metabolomics and (2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.

  10. Induction of a Stringent Metabolic Response in Intracellular Stages of Leishmania mexicana Leads to Increased Dependence on Mitochondrial Metabolism

    Science.gov (United States)

    Saunders, Eleanor C.; Ng, William W.; Kloehn, Joachim; Chambers, Jennifer M.; Ng, Milica; McConville, Malcolm J.

    2014-01-01

    Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using 13C-stable isotope resolved metabolomics and 2H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate) and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA) cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism. PMID:24465208

  11. Assessing Metabolic Syndrome Through Increased Heart Rate During Exercise.

    Science.gov (United States)

    Sadeghi, Masoumeh; Gharipour, Mojgan; Nezafati, Pouya; Shafie, Davood; Aghababaei, Esmaeil; Sarrafzadegan, Nizal

    2016-11-01

    The present study aimed to assess changes in resting and maximum heart rates as primary indicators of cardiac autonomic function in metabolic syndrome (MetS) patients and to determine their value for discriminating MetS from non-MetS. 468 participants were enrolled in this cross-sectional study and assessed according to the updated adult treatment panel III (ATP-III) definition of MetS. Resting and maximum heart rates were recorded following the Bruce protocol during an exercise. A receiver operating characteristic (ROC) curve was used to identify the best cutoff point for discriminating MetS from the non-MetS state. 194 participants (41.5%) were diagnosed as MetS. The mean resting heart rate (RHR) was not statistically different between the two groups (P=0.078). However, the mean maximum heart (MHR) rate was considerably higher in participants with MetS (142.37±14.84 beats per min) compared to the non-MetS group (134.62±21.63 beats per min) (P<0.001). In the MetS group, the MHR was positively correlated with the serum triglyceride level (β=0.185, P=0.033) and was inversely associated with age (β=-0.469, P<0.001). The MHR had a moderate value for discriminating MetS from the non-MetS state (c=0.580, P=0.004) with the optimal cutoff point of 140 beats per min. In MetS patients, the MHR was significantly greater compared to non-MetS subjects and was directly correlated with serum triglyceride levels and inversely with advanced age. Moreover, MHR can be used as a suspicious indicator for identifying MetS.

  12. [Function of pancreas transplants in increased metabolic stress].

    Science.gov (United States)

    Teuscher, A U; Seaquist, E R; Barrou, Z; Kendall, D M; Robertson, R P

    1995-01-01

    Patients undergoing successful pancreas transplantation have normal glucose levels in the fasting and fed states and normal levels of hemoglobin A1c without use of exogenous inulin or any other medications for diabetes. In some of these patients, these measures have remained stable for more than 10 years. Additionally pancreas transplant recipients recover from short-term hypoglycemia produced by an intravenous pulse of insulin. However, metabolic success has been determined by relatively routine, unsophisticated tests such as oral and intravenous glucose tolerance tests or stimulation with intravenous arginine. These tests may not provide measures of the functional reserve of the pancreas, which is called on during periods of maximal stress. Consequently, we designed studies to ascertain beta and alpha cell performance in recipients of whole pancreas transplants and recipients of a segment of a living related donor. All recipients were recruited from the University of Minnesota Transplant Registry, Minneapolis, Minnesota. Successfully transplanted recipients were subjected to prolonged hyperglycemia to assess insulin secretory reserve using the method of glucose potentiation of arginine induced insulin secretion and to prolonged hypoglycemia to assess glucagon responsiveness and hepatic glucose production using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show that pancreas transplant recipients have markedly diminished insulin secretory reserve, a defect not evident with conventional tests of beta-cell function. No difference was found between the whole graft and segmental graft recipients. Pancreas transplantation restores the defective glucagon secretory response and enhances hepatic glucose production during prolonged hypoglycemia in subjects with type I diabetes. We conclude that pancreas transplantation does not completely restore beta-cell secretory reserve. This defect might be probably caused in part by cyclosporine and by the

  13. Assessing Metabolic Syndrome Through Increased Heart Rate During Exercise

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2016-12-01

    Full Text Available The present study aimed to assess changes in resting and maximum heart rates as primary indicators of cardiac autonomic function in metabolic syndrome (MetS patients and to determine their value for discriminating MetS from non-MetS. 468 participants were enrolled in this cross-sectional study and assessed according to the updated adult treatment panel III (ATP-III definition of MetS. Resting and maximum heart rates were recorded following the Bruce protocol during an exercise. A receiver operating characteristic (ROC curve was used to identify the best cutoff point for discriminating MetS from the non-MetS state. 194 participants (41.5% were diagnosed as MetS. The mean resting heart rate (RHR was not statistically different between the two groups (P=0.078. However, the mean maximum heart (MHR rate was considerably higher in participants with MetS (142.37±14.84 beats per min compared to the non-MetS group (134.62±21.63 beats per min (P<0.001. In the MetS group, the MHR was positively correlated with the serum triglyceride level (β=0.185, P=0.033 and was inversely associated with age (β=-0.469, P<0.001. The MHR had a moderate value for discriminating MetS from the non-MetS state (c=0.580, P=0.004 with the optimal cutoff point of 140 beats per min. In MetS patients, the MHR was significantly greater compared to non-MetS subjects and was directly correlated with serum triglyceride levels and inversely with advanced age. Moreover, MHR can be used as a suspicious indicator for identifying MetS.

  14. Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum.

    Science.gov (United States)

    Smith, Samantha K; Lee, Christie A; Dausch, Matthew E; Horman, Brian M; Patisaul, Heather B; McCarty, Gregory S; Sombers, Leslie A

    2017-02-15

    Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.

  15. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    Energy Technology Data Exchange (ETDEWEB)

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. (Univ. of California, San Francisco (USA))

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  16. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    Science.gov (United States)

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E

    2014-07-01

    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  17. [Increased urinary sodium excretion in the early phase of aneurysmal subarachnoid hemorrhage as a predictor of cerebral salt wasting syndrome].

    Science.gov (United States)

    Nakagawa, Ichiro; Kurokawa, Shinichiro; Takayama, Katsutoshi; Wada, Takeshi; Nakase, Hiroyuki

    2009-12-01

    Cerebral salt wasting syndrome (CSWS) in patients with aneurysmal subarachnoid hemorrhage (SAH) is considered to correlate with delayed ischemic neurological deficits (DIND) induced by cerebral vasospasm; however, its exact mechanism is still not well-known. The purpose of the present study is to evaluate the relationship between hyponatremia caused by CSWS and the increase of the urinary sodium excretion in early phase following SAH. Fifty-four patients with SAH were divided into 2 groups, normonatremia group and hyponatremia group which suffered hyponatremia after SAH. The hyponatremia group comprise 14 patients (26%) in whom the hyponatremia developed of the SAH. In this group, the serum level of sodium significantly decreased 7 days after SAH and then gradually normalised. Further, excretion of sodium in the urine tended to increase 3 days after SAH and significantly increased 7 days after SAH. In conclusion, the increased urinary sodium excretion in the early phase of SAH would serve as a predictive factor for CSWS after SAH. We consider that it is important to start sodium and fluid supplementation and inhibit natriuresis by fludrocortisone acetate administration before hyponatremia occurs in order to prevention delayed ischemic neurological deficits in SAH patients.

  18. Explosive resistance training increases rate of force development in ankle dorsiflexors and gait function in adults with cerebral palsy

    DEFF Research Database (Denmark)

    Kirk, Henrik; Geertsen, Svend Sparre; Lorentzen, Jakob

    2016-01-01

    Alterations in passive elastic properties of muscles and reduced ability to quickly generate muscle force contribute to impaired gait function in adults with cerebral palsy (CP). Here, we investigated if 12 weeks of progressive and explosive resistance training (PRT) increases rate of force...... dorsiflexion, plantarflexion, leg press, hamstring curls, abdominal curls and back extension 3 days/week for 12 weeks, with 3 sets per exercise and progressing during the training period from 12-6 RM. RFDdf, 3-D gait analysis, functional performance and ankle joint passive- and reflex-mediated muscle stiffness...

  19. 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.)

  20. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism

    Science.gov (United States)

    The common parasite Toxoplasma gondii induces behavioral alterations in its hosts including phenotypes increasing the likelihood of its transmission in rodents and reports of psychobehavioral alterations in humans. We have found that elevated levels of dopamine are associated with the encysted stage...

  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. 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.

  4. Treatment of human muscle cells with popular dietary supplements increase mitochondrial function and metabolic rate

    Directory of Open Access Journals (Sweden)

    Vaughan Roger A

    2012-11-01

    Full Text Available Abstract Background Obesity is a common pathology with increasing incidence, and is associated with increased mortality and healthcare costs. Several treatment options for obesity are currently available ranging from behavioral modifications to pharmaceutical agents. Many popular dietary supplements claim to enhance weight loss by acting as metabolic stimulators, however direct tests of their effect on metabolism have not been performed. Purpose This work identified the effects popular dietary supplements on metabolic rate and mitochondrial biosynthesis in human skeletal muscle cells. Methods Human rhabdomyosarcoma cells were treated with popular dietary supplements at varied doses for 24 hours. Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α, an important stimulator of mitochondrial biosynthesis, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was measured using flow cytometry confirmed with confocal microscopy. Glycolytic metabolism was quantified by measuring extracellular acidification rate (ECAR and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR. Total relative metabolism was quantified using WST-1 end point assay. Results Treatment of human rhabdomyosarcoma cells with dietary supplements OxyElite Pro (OEP or Cellucore HD (CHD induced PGC-1α leading to significantly increased mitochondrial content. Glycolytic and oxidative capacities were also significantly increased following treatment with OEP or CHD. Conclusion This is the first work to identify metabolic adaptations in muscle cells following treatment with popular dietary supplements including enhanced mitochondrial biosynthesis, and glycolytic, oxidative and total metabolism.

  5. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine

    DEFF Research Database (Denmark)

    Leke, Renata; Bak, Lasse Kristoffer; Anker, Malene

    2011-01-01

    in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure...... enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important......Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme...

  6. Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network

    DEFF Research Database (Denmark)

    Østergaard, Simon; Olsson, Lisbeth; Johnston, M.

    2000-01-01

    in the pathway, and ultimately, increasing metabolic flux through the pathway of interest, By manipulating the GAL gene regulatory network of Saccharomyces cerevisiae, which is a tightly regulated system, we produced prototroph mutant strains, which increased the flux through the galactose utilization pathway...... media. The improved galactose consumption of the gal mutants did not favor biomass formation, but rather caused excessive respiro-fermentative metabolism, with the ethanol production rate increasing linearly with glycolytic flux....

  7. 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.)

  8. ''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

  9. Age-related alterations in behavioral and cerebral metabolic responses to the serotonin agonist meta-chlorophenylpiperazine in rats.

    Science.gov (United States)

    Freo, U; Rapoport, S I; Soncrant, T T

    1991-01-01

    To determine the functional relevance of the age-related neurochemical changes that occur in brain serotonin systems during aging, we measured the effects of the serotonin receptor agonist meta-chlorophenylpiperazine (MCPP) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in awake rats. rCMRglc was determined in 74 regions of Fischer-344 rats aged 3, 12 and 24 months, at 15 and 90 min after MCPP 2.5 mg/kg IP, using the quantitative, autoradiographic [14C]2-deoxy-D-glucose technique. The time-course of motor performance following MCPP was assessed with a rotating rod. MCPP impaired motor performance in all ages maximally at 15-30 min. Three-month-old rats recovered completely within 60 min, whereas 12-month-old animals exhibited partial recovery and 24-month-old rats did not recover by 120 min. At 15 min after MCPP, rCMRglc was reduced in 51 of the 74 studied regions (overall decrease, 20%) of 3-month-old rats, in 21 regions (13% decrease) of 12-month-old rats and in 14 regions (2% decrease) of 24-month-old animals. Similar MCPP brain concentrations were achieved at 15 min in rats of all ages. The results suggest that the functional integrity of serotonergic transmission is reduced in aged rats and that the dysregulation is presynaptic.

  10. Cerebral metabolic responses to meta-chlorophenylpiperazine are reduced during its chronic administration to young and aged rats.

    Science.gov (United States)

    Freo, U; Larson, D M; Soncrant, T T

    1993-01-01

    The effects of the 5-HT agonist meta-chlorophenylpiperazine (MCPP) on regional cerebral metabolic rates for glucose (rCMRglc) were measured in 3- and 24-month-old rats that were not pretreated or were pretreated for 2 weeks with continuous infusion of saline or MCPP. rCMRglc were measured using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique in 71 brain regions at 15 min after acute administration of MCPP 2.5 mg/kg. In the absence of chronic pretreatment, intraperitoneal MCPP 2.5 mg/kg produced widespread rCMRglc reductions (41 brain areas) in 3-month-old rats and more limited rCMRglc decreases (8 brain areas) in 24-month-old rats. After chronic treatment, MCPP failed to reduce rCMRglc in any region of either group of rats. These findings indicate that mechanisms of downregulation of response to MCPP are functional in young and aged rats and suggest that the age-related reduction in rCMRglc responses to acute MCPP in non-pretreated animals may be due to compensation for age-related losses of 5-HT terminals.

  11. 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

    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...... 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...... media. Based on the measured (13)C-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 (13)C-labeling observed with [U-(13)C...

  12. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    Science.gov (United States)

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  13. Explosive Resistance Training Increases Rate of Force Development in Ankle Dorsiflexors and Gait Function in Adults With Cerebral Palsy.

    Science.gov (United States)

    Kirk, Henrik; Geertsen, Svend S; Lorentzen, Jakob; Krarup, Kasper B; Bandholm, Thomas; Nielsen, Jens B

    2016-10-01

    Kirk, H, Geertsen, SS, Lorentzen, J, Krarup, KB, Bandholm, T, and Nielsen, JB. Explosive resistance training increases rate of force development in ankle dorsiflexors and gait function in adults with cerebral palsy. J Strength Cond Res 30(10): 2749-2760, 2016-Alterations in passive elastic properties of muscles and reduced ability to quickly generate muscle force contribute to impaired gait function in adults with cerebral palsy (CP). In this study, we investigated whether 12 weeks of explosive and progressive heavy-resistance training (PRT) increases rate of force development of ankle dorsiflexors (RFDdf), improves gait function, and affects passive ankle joint stiffness in adults with CP. Thirty-five adults (age: 36.5; range: 18-59 years) with CP were nonrandomly assigned to a PRT or nontraining control (CON) group in this explorative trial. The PRT group trained ankle dorsiflexion, plantarflexion, leg press, hamstring curls, abdominal curls, and back extension 3 days per week for 12 weeks, with 3 sets per exercise and progressing during the training period from 12 to 6 repetition maximums. RFDdf, 3-dimensional gait analysis, functional performance, and ankle joint passive and reflex-mediated muscle stiffness were evaluated before and after. RFDdf increased significantly after PRT compared to CON. PRT also caused a significant increase in toe lift late in swing and a significantly more dorsiflexed ankle joint at ground contact and during stance. The increased toe-lift amplitude was correlated to the increased RFDdf (r = 0.73). No other between-group differences were observed. These findings suggest that explosive PRT may increase RFDdf and facilitate larger range of movement in the ankle joint during gait. Explosive PRT should be tested in clinical practice as part of a long-term training program for adults with CP.

  14. Lactate as a cerebral metabolic fuel for glucose-6-phosphatase deficient children.

    Science.gov (United States)

    Fernandes, J; Berger, R; Smit, G P

    1984-04-01

    The main substrates for brain energy metabolism were measured in blood samples taken from the carotid artery and the internal jugular bulb of four children with glycogen storage disease caused by deficiency of glucose-6-phosphatase. Multiple paired arterial and venous blood samples were analyzed for glucose, lactate, pyruvate, D-beta-hydroxybutyrate, acetoacetate, glycerol and O2, and the arteriovenous differences of the concentrations were calculated. In the first three patients the substrates were measured in two successive conditions with lower and higher glucose-intake, respectively, inducing reciprocally higher and lower concentrations of blood lactate. In the fourth patient medium chain triglycerides were administered simultaneously with the glucose-containing gastric drip feeding. Lactate appeared to be taken up significantly. It consumed, if completely oxidized, between 40-50% of the total O2 uptake in most cases. Only once in one patient the uptake of lactate switched to its release, when the blood lactate level decreased to normal. D-beta-hydroxybutyrate and acetoacetate arteriovenous (A-V) differences were small to negligible and these ketone bodies, therefore, did not contribute substantially to the brain's energy expenditure. Glycerol was not metabolized by the brain. Lactate thus appeared to be the second brain fuel next to glucose. It may protect the brain against fuel depletion in case of hypoglycemia.

  15. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone.

    Science.gov (United States)

    Krieger, Nancy S; Culbertson, Christopher D; Kyker-Snowman, Kelly; Bushinsky, David A

    2012-08-01

    Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality.

  16. 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.)

  17. Severe cerebral congophilic angiopathy coincident with increased brain aluminium in a resident of Camelford, Cornwall, UK.

    Science.gov (United States)

    Exley, C; Esiri, M M

    2006-07-01

    In July 1988, 20 tonnes of aluminium sulphate was discharged by the South West Water Authority into the drinking water supplied to a large region of North Cornwall. Up to 20,000 people were exposed to concentrations of aluminium which were 500-3000 times the acceptable limit under European Union legislation (0.200 mg/l). Although this incident is currently the topic of a government inquiry, nothing is known about its longer-term repercussions on human health. The first neuropathological examination of a person who was exposed and died of an unspecified neurological condition was carried out. A rare form of sporadic early-onset beta amyloid angiopathy in cerebral cortical and leptomeningeal vessels, and in leptomeningeal vessels over the cerebellum was identified. In addition, high concentrations of aluminium were found coincident with the severely affected regions of the cortex. Although the presence of aluminium is highly unlikely to be adventitious, determining its role in the observed neuropathology is impossible. A clearer understanding of aluminium's role in this rare form of Alzheimer's related disease should be provided by future research on other people from the exposed population as well as similar neuropathologies in people within or outside this group.

  18. 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

    The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

  19. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    Science.gov (United States)

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  20. LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex.

    Science.gov (United States)

    Nimmervoll, Birgit; White, Robin; Yang, Jenq-Wei; An, Shuming; Henn, Christopher; Sun, Jyh-Jang; Luhmann, Heiko J

    2013-07-01

    During the pre- and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor α and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.

  1. Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with {sup 15}O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hiroshi [Department of Radiology and Nuclear Medicine, Akita Research Institute of Brain and Blood Vessels, Akita (Japan); Department of Nuclear Medicine and Radiology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-Machi, 980-8575, Aoba-Ku, Sendai (Japan); Kanno, Iwao [Department of Radiology and Nuclear Medicine, Akita Research Institute of Brain and Blood Vessels, Akita (Japan); Kato, Chietsugu [Department of Nuclear Medicine, Hokkaido University School of Medicine, Sapporo (Japan); Sasaki, Toshiaki [Cyclotoron Research Center, Iwate Medical University, Morioka (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo (Japan); Ouchi, Yasuomi [Positron Medical Center, Hamamatsu Medical Center, Hamakita (Japan); Iida, Akihiko [Nagoya City Rehabilitation Center, Nagoya (Japan); Okazawa, Hidehiko [PET Unit, Research Institute, Shiga Medical Center, Moriyama (Japan); Hayashida, Kohei [Department of Radiology, National Cardiovascular Center, Suita, Osaka (Japan); Tsuyuguchi, Naohiro [Department of Neurosurgery, Osaka City University Medical School, Osaka (Japan); Ishii, Kazunari [Division of Imaging Research, Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Hyogo (Japan); Kuwabara, Yasuo [Department of Radiology, Faculty of Medicine, Kyushu University, Fukuoka (Japan); Senda, Michio [Department of Image-based Medicine, Institute of Biomedical Research and Innovation, Kobe (Japan)

    2004-05-01

    Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C{sup 15}O{sub 2}) or {sup 15}O-labelled water (H{sub 2}{sup 15}O), {sup 15}O-labelled carbon monoxide (C{sup 15}O) and {sup 15}O-labelled oxygen ({sup 15}O{sub 2}) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of {sup 15}O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C{sup 15}O{sub 2} (or H{sub 2}{sup 15}O) and {sup 15}O{sub 2}. All used C{sup 15}O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8{+-}15.1 years). Overall mean{+-}SD values for cerebral cortical regions were: CBF=44.4{+-}6.5 ml 100 ml{sup -1} min{sup -1}; CBV=3.8{+-}0.7 ml 100 ml{sup -1}; OEF=0.44{+-}0.06; CMRO{sub 2}=3.3{+-}0.5 ml 100 ml{sup -1} min{sup -1}. Significant between-centre variation was observed in CBV, OEF and CMRO{sub 2} by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO{sub 2} was acceptably small. Building a database of normal cerebral haemodynamics obtained by the{sup 15}O-PET methods may be practicable. (orig.)

  2. Cerebral palsy in eastern Denmark: declining birth prevalence but increasing numbers of unilateral cerebral palsy in birth year period 1986-1998

    DEFF Research Database (Denmark)

    Ravn, Susanne Holst; Flachs, Esben Meulengracht; Uldall, Peter

    2010-01-01

    The Cerebral Palsy Registry in eastern Denmark has been collecting cases using a uniform data sampling procedure since birth year 1979. Children are included by two child neurologists and an obstetrician. Information on pregnancy, birth, neonatal period, impairments and demographic data...... are registered. The total cerebral palsy birth prevalence has been significantly decreasing since the birth period 1983-1986 with 3.0 per 1000 live births until the period 1995-1998 with 2.1 per 1000 live births. The overall decrease was seen in preterm infants (...

  3. Increased Cerebral Tff1 Expression in Two Murine Models of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eva B Znalesniak

    2016-11-01

    Full Text Available Background/Aims: The trefoil factor family (TFF peptide TFF1 is a typical secretory product of the gastric mucosa and a very low level of expression occurs in nearly all regions of the murine brain. TFF1 possesses a lectin activity and binding to a plethora of transmembrane glycoproteins could explain the diverse biological effects of TFF1 (e.g., anti-apoptotic effect. It was the aim to test whether TFF expression is changed during neuroinflammation. Methods: Expression profiling was performed using semi-quantitative RT-PCR analyses in two murine models of neuroinflammation, i.e. Toxoplasma gondii-induced encephalitis and experimental autoimmune encephalomyelitis (EAE, the latter being the most common animal model of multiple sclerosis. Tff1 expression was also localized using RNA in situ hybridization histochemistry. Results: We report for the first time on a significant transcriptional induction in cerebral Tff1 expression in both T. gondii-induced encephalitis and EAE. In contrast, Tff2 and Tff3 expression were not altered. Tff1 transcripts were predominantly localized in the internal granular layer of the cerebellum indicating neuronal expression. Furthermore, also glial cells are expected to express Tff1. Characterization of both experimental models by expression profiling (e.g., inflammasome sensors, inflammatory cytokines, microglial marker Iba1, ependymin related protein 1 revealed differences concerning the expression of the inflammasome sensor Nlrp1 and interleukin 17a. Conclusion: The up-regulated expression of Tff1 is probably the result of a complex inflammatory process as its expression is induced by tumor necrosis factor α as well as interleukins 1β and 17. However on the transcript level, Tff1KO mice did not show any significant signs of an altered immune response after infection with T. gondii in comparison with the wild type animals.

  4. Face cooling with mist water increases cerebral blood flow during exercise: Effect of changes in facial skin blood flow

    Directory of Open Access Journals (Sweden)

    Taiki eMiyazawa

    2012-08-01

    Full Text Available Facial cooling (FC increases cerebral blood flow (CBF at rest and during exercise; however, the mechanism of this response remains unclear. The purpose of the present study was to test our hypothesis that FC causes facial vasoconstriction that diverts skin blood flow (SkBFface towards the middle cerebral artery (MCA Vmean at rest and to a greater extent during exercise. Nine healthy young subjects (20 ± 2 yrs. underwent 3 minutes of FC by fanning and spraying the face with a mist of cold water (~4˚C at rest and during steady-state exercise (heart rate of 120 bpm. We focused on the difference between the averaged data acquired from 1 min immediately before FC and last 1 min of FC. SkBFface, MCA Vmean and MAP were higher during exercise than at rest. As hypothesized, FC decreased SkBFface at rest (-32 ± 4 % and to a greater extent during exercise (-64 ± 10%, P=0.012. Although MCA Vmean was increased by FC (Rest, +1.4 ± 0.5 cm/s; Exercise, +1.4 ± 0.6 cm/s, the amount of the FC-evoked changes in MCA Vmean at rest and during exercise differed among subjects. In addition, changes in MCA Vmean with FC did not correlate with concomitant changes in SkBFface (r=0.095, P=0.709. MAP was also increased by FC (Rest, +6.2 ± 1.4 mmHg; Exercise, +4.2 ± 1.2 mmHg. These findings suggest that the FC induced increase in CBF during exercise could not be explained only by change in SkBFface.

  5. 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.

  6. Interregional cerebral metabolic associativity during a continuous performance task (Part I): healthy adults.

    Science.gov (United States)

    Willis, Mark W; Benson, Brenda E; Ketter, Terence A; Kimbrell, Tim A; George, Mark S; Speer, Andrew M; Herscovitch, Peter; Post, Robert M

    2008-10-30

    One emerging hypothesis regarding psychiatric illnesses is that they arise from the dysregulation of normal circuits or neuroanatomical patterns. In order to study mood disorders within this framework, we explored normal metabolic associativity patterns in healthy volunteers as a prelude to examining the same relationships in affectively ill patients (Part II). We applied correlational analyses to regional brain activity as measured with FDG-PET during an auditory continuous performance task (CPT) in 66 healthy volunteers. This simple attention task controlled for brain activity that otherwise might vary amongst affective and cognitive states. There were highly significant positive correlations between homologous regions in the two hemispheres in thalamic, extrapyramidal, orbital frontal, medial temporal and cerebellar areas. Dorsal frontal, lateral temporal, cingulate, and especially insula, and inferior parietal areas showed less significant homologous associativity, suggesting more specific lateralized function. The medulla and bilateral thalami exhibited the most diverse interregional associations. A general pattern emerged of cortical regions covarying inversely with subcortical structures, particularly the frontal cortex with cerebellum, amygdala and thalamus. These analytical data may help to confirm known functional and neuroanatomical relationships, elucidate others as yet unreported, and serve as a basis for comparison to patients with psychiatric illness.

  7. 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

    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...... infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy...

  8. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length.

    Science.gov (United States)

    Smith, Lucas R; Lee, Ki S; Ward, Samuel R; Chambers, Henry G; Lieber, Richard L

    2011-05-15

    Cerebral palsy (CP) results from an upper motoneuron (UMN)lesion in the developing brain. Secondary to the UMNl esion,which causes spasticity, is a pathological response by muscle - namely, contracture. However, the elements within muscle that increase passive mechanical stiffness, and therefore result in contracture, are unknown. Using hamstring muscle biopsies from pediatric patients with CP (n =33) and control (n =19) patients we investigated passive mechanical properties at the protein, cellular, tissue and architectural levels to identify the elements responsible for contracture. Titin isoform, the major load-bearing protein within muscle cells, was unaltered in CP. Correspondingly, the passive mechanics of individual muscle fibres were not altered. However, CP muscle bundles, which include fibres in their constituent ECM, were stiffer than control bundles. This corresponded to an increase in collagen content of CP muscles measured by hydroxyproline assay and observed using immunohistochemistry. In vivo sarcomere length of CP muscle measured during surgery was significantly longer than that predicted for control muscle. The combination of increased tissue stiffness and increased sarcomere length interact to increase stiffness greatly of the contracture tissue in vivo. These findings provide evidence that contracture formation is not the result of stiffening at the cellular level, but stiffening of the ECM with increased collagen and an increase of in vivo sarcomere length leading to higher passive stresses.

  9. Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes

    Science.gov (United States)

    Zanchi, Davide; Viallon, Magalie; Le Goff, Caroline; Millet, Grégoire P.; Giardini, Guido; Croisille, Pierre; Haller, Sven

    2017-01-01

    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due

  10. 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.)

  11. Tin chloride enhances parvalbumin-positive interneuron survival by modulating heme metabolism in a model of cerebral ischemia.

    Science.gov (United States)

    Li Volti, Giovanni; Zappalà, Agata; Leggio, Gian Marco; Mazzola, Carmen; Drago, Filippo; La Delia, Francesco; Serapide, Maria Francesca; Pellitteri, Rosalia; Giannone, Ignazio; Spatuzza, Michela; Cicirata, Valentina; Cicirata, Federico

    2011-03-29

    SnCl(2) has been reported to increase the expression of heme-oxygenase 1 (HO-1), a major antioxidant enzyme, and to decrease ischemic injury, in non-nervous tissues. This study examined the neuroprotective effect of SnCl(2) in the hippocampus of rats submitted to cerebral ischemia. SnCl(2) was administered 18 h before bilateral carotids obstruction. Changes in HO-1 expression and activity, heme content, inducible nitric oxide synthase (iNOS) expression and parvalbumin positive interneuron survival were studied. Thereafter both behavior and memory recovery were tested. The administration of SnCl(2) increased the expression of HO-1 protein and HO activity in the hippocampus and concomitantly decreased heme content at both mitochondrial and nuclear level. Furthermore, ischemized animals showed a strong increase in iNOS expression in the hippocampus, where a loss of parvalbumin positive interneurons also occurred. Pre-treatment with SnCl(2), decreased both iNOS expression in ischemized rats and increased cell survival. The beneficial effects of SnCl(2) were prevented by concomitant treatment with SnMP, a strong inhibitor of HO activity. SnCl(2) also caused an improvement in short term memory recovery. Our results showed that following SnCl(2) administration, HO-1 is strongly induced in the hippocampus and modulate iNOS expression, resulting in a strong neuroprotective effect.

  12. Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial.

    Science.gov (United States)

    Arba, Francesco; Mair, Grant; Carpenter, Trevor; Sakka, Eleni; Sandercock, Peter A G; Lindley, Richard I; Inzitari, Domenico; Wardlaw, Joanna M

    2017-07-01

    Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear. We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters. We examined associations between SVD features (individually and summed) and presence of hypoperfusion using logistic regression adjusted for age, sex, baseline National Institutes of Health Stroke Scale, hypertension, and diabetes. A total of 115 patients with median (interquartile range) age of 81 (72-86) years, 78 (52%) of which were male, had complete perfusion data. Hypoperfusion was most frequent on mean transit time (MTT; 63 patients, 55%) and least frequent on time to maximum flow (19 patients, 17%). The SVD score showed stronger independent associations with hypoperfusion (e.g., MTT, odds ratio [OR] = 2.80; 95% confidence interval [CI] = 1.56-5.03) than individual SVD markers (e.g., white matter hypoattenuation score, MTT, OR = 1.49, 95% CI = 1.09-2.04). Baseline blood pressure did not differ by presence or absence of hypoperfusion or across strata of SVD score. Presence of white matter hypoperfusion increased with SVD summed score. The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation.

    Science.gov (United States)

    Song, T-J; Kim, J; Lee, H S; Nam, C M; Nam, H S; Heo, J H; Kim, Y D

    2013-03-01

    Cerebral microbleeds (CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation (OA)-related intracranial haemorrhage (ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS(2) scores or CHA(2) DS(2) -VASc scores in non-valvular atrial fibrillation (NVAF) patients. We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging (MRI) with gradient-recalled echo (GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS(2) scores and CHA(2) DS(2) -VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up. The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS(2) scores or CHA(2) DS(2) -VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS(2) scores or CHA(2) DS(2) -VASc scores were not. Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  14. Increased fat oxidation and regulation of metabolic genes with ultraendurance exercise

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Rehrer, N J; Pilegaard, H

    2007-01-01

    AIM: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. METHODS: Data were...... exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes....

  15. Metabolism

    Science.gov (United States)

    ... Surgery? Choosing the Right Sport for You Shyness Metabolism KidsHealth > For Teens > Metabolism Print A A A ... food through a process called metabolism. What Is Metabolism? Metabolism (pronounced: meh-TAB-uh-lih-zem) is ...

  16. Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

    DEFF Research Database (Denmark)

    Hansen, M B; Olsen, Niels Vidiendal; Hyldegaard, O

    2013-01-01

    Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN...

  17. Effect of fasudil combined with conventional therapy on nerve and blood coagulation function as well as Hcy metabolism in patients with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Zhi-Yong Lu

    2017-01-01

    Objective:To analyze the effect of fasudil combined with conventional therapy on nerve and blood coagulation function as well as Hcy metabolism in patients with acute cerebral infarction. Methods:80 patients with acute cerebral infarction treated in our hospital between January 2013 and January 2013 were selected as the research subjects and divided into observation group (n = 40) and control group (n = 40) according to the random number table. Control group received conventional therapy and observation group received fasudil combined with conventional therapy. After 14 d of treatment, the levels of cerebral blood perfusion parameters, nerve function indexes, platelet function indexes and homocysteine (Hcy) of two groups of patients were determined.Results:After 14 d of treatment, middle cerebral artery and basilar artery peak systolic flow velocity (Vs), low diastolic flow velocity (Vd) and mean flow velocity (Vm) levels of observation group were higher than those of control group (P<0.05); serum nerve function indexes brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) content were higher than those of control group (P<0.05) while phosphatidic acid (PA), neuron-specific enolase (NSE), S100β protein (S100β), and substantia nigra divalent metal transporter 1 (DMT1) content were lower than those of control group (P<0.05); serum platelet function indexes platelet activation-dependent granule membrane protein-140 (GMP-140), fibrinogen receptor-1 (PAC-1), platelet activating factor (PAF) and platelet-derived growth factor BB (PDGF-BB) content were lower than those of control group (P<0.05); serum Hcy content was lower than that of control group (P<0.05).Conclusions:Fasudil combined with conventional therapy can optimize the nerve function and blood coagulation function in patients with acute cerebral infarction, and also plays a positive role in reducing Hcy levels.

  18. Development of a NIRS method to quantify cerebral perfusion and oxidative metabolism in preterm infants with post-hemorrhagic ventricle dilation (Conference Presentation)

    Science.gov (United States)

    McLachlan, Peter; Kishimoto, Jessica; de Ribeaupierre, Sandrine; Lee, David S. C.; Diop, Mamadou; St Lawrence, Keith

    2017-02-01

    A complication of intraventricular hemorrhage among preterm neonates is post-hemorrhagic ventricle dilation (PHVD), which is associated with a greater risk of life-long neurological disability. Clinical evidence, including suppressed EEG patterns, suggests that cerebral perfusion and oxygenation is impaired in these patients, likely due to elevated intracranial pressure (ICP). Cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2) can be quantified by dynamic contrast-enhanced NIRS; however, PHVD poses a unique challenge to NIRS since the cerebral mantle can be compressed to 1 cm or less. The objectives of this work were to develop a finite-slab model for the analysis of NIRS spectra, incorporating depth measurements from ultrasound images, and to assess the magnitude of error when using the standard semi-infinite model. CBF, tissue saturation (StO2) and CMRO2 were measured in 9 patients receiving ventricle taps to reduce ICP. Monte Carlo simulations indicated that errors in StO2 could be greater than 20% if the cerebral mantle was reduced to 1 cm. Using the finite-slab model, basal CBF and CMRO2 in the PHVD patients were not significantly different from a control group of preterm infants (14.6 ± 4.2 ml/100 g/min and 1.0 ± 0.4 ml O2/100 g/min), but StO2 was significantly lower (PDA 70.5 ± 9%, PHVD 58.9 ± 12%). Additionally, ventricle tapping improved CBF by 15.6 ± 22%. This work indicates that applying NIRS to PHVD patients is prone to error; however, this issue can be overcome with the appropriate model and using readily available ultrasound images.

  19. Oral Levosimendan Increases Cerebral Blood Flow Velocities in Patients with a History of Stroke or Transient Ischemic Attack: A Pilot Safety Study

    Directory of Open Access Journals (Sweden)

    Matti Kivikko, MD, PhD

    2015-12-01

    Conclusions: Oral levosimendan increases cerebral blood flow velocities and diminishes NT-pro-BNP levels in patients with earlier ischemic cerebrovascular event. Daily doses up to 1.0 mg were well tolerated, whereas the 2.0 mg dose level induced an increase in ventricular extrasystoles. ClinicalTrials.gov identifier: NCT00698763.

  20. Cerebral Oxygenation and Oxygen Extraction in the Preterm Infant during Desaturation : Effects of Increasing FiO(2) to Assist Recovery

    NARCIS (Netherlands)

    Baerts, Willem; Lemmers, Petra M. A.; van Bel, Frank

    2011-01-01

    Background: In the clinical setting, episodes of desaturation in newborn infants are often treated by increasing the fraction of inspired oxygen (FiO(2)). Objectives: To study the effect of an increase in FiO(2) on cerebral oxygenation during recovery from desaturation, as measured by near-infrared

  1. Cerebral blood flow and oxygen metabolism in patients with dementia of the Alzheimer's type by position emission tomography using 0-15 steady state technique

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Shizuki; Kitamura, Shin; Ujike, Takashi; Terashi, Akiro; Iio, Masaaki.

    1988-07-01

    In 12 patients with dementia of the Alzheimer's type (DAT) and 5 age-matched healthy subjects, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), and cerebral oxygen consumption (rCMRO/sub 2/) were determined using positron emission tomography (PET) with 0-15 labeled CO/sub 2/ and O/sub 2/ inhalation method. There was a significant reduction in CMRO/sub 2/ of the temporal cortex in the group of mild DAT compared with the control group. In the group of moderate DAT, CBF of the temporal cortex and CMRO/sub 2/ of the temporal and parietal cortices were significantly reduced. The group of severe DAT showed a significantly reduced CBF and CMRO/sub 2/ in the frontal cortex, and a relatively spared occipital cortex in all stages. The results indicated that metabolic reduction in the temporal cortex first occurs, and that metabolic dysfunction in the parietal and frontal cortices results in blood flow reduction and deterioration of DAT. Right/left metabolic asymmetry in the temporal and parietal cortices was correlated with language and visuospatial functions. (Namekawa, K).

  2. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.

    Science.gov (United States)

    Choi, S; Sainz, B; Corcoran, P; Uprichard, S; Jeong, H

    2009-03-01

    The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model.

  3. Metabolic Changes in Rats with Photochemically Induced Cerebral Infarction and the Effects of Batroxobin: A Study by Magnetic Resonance Imaging, 1H- and 31P- Magnetic Resonance Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    管兴志; 吴卫平; 匡培根; 匡培梓; 高杨; 管林初; 李丽云; 毛希安; 刘买利

    2001-01-01

    Metabolic changes in rats with photochemically induced cerebral infarction and the effects of batroxobin were investigated 1, 3, 5 and 7 days after infarction by means of magnetic resonance imaging (MRI), 1H- and 31P- magnetic resonance spectroscopy (MRS). A region of T2 hyperintensity was observed in left temporal neocortex in infarction group and batroxobin group 1, 3, 5 and 7 days after infarction. The volume of the region gradually decreased from 1 day to 7 days after infarction. The ratio of NAA/Cho+Cr in the region of T2 hyperintensity in the infarction group was significantly lower than that in the corresponding region in the sham-operated group 3, 5 and 7 days after infarction respectively (P<0.05). Lac appeared in the region of T2 hyperintensity in the infarction group 1, 3, 5 and 7 days after infarction, but it was not observed in the corresponding region in sham-operated group at all time points. Compared with the sham-operated group, the ratios of bATP/PME+PDE and PCr/PME+PDE of the whole brain in the infarction group were significantly lower 1, 3 and 5 days after infarction respectively (P<0.05), and the ratio of bATP/PCr also was significantly lower 1 day after infarction (P<0.05). Batroxobin significantly decreased the volume of the region of T2 hyperintensity 1 and 3 days after infarction (P<0.05), significantly increased the ratio of NAA/Cho+Cr in the region 5 and 7 days after infarction (P<0.05), significantly decreased the ratios of Lac/Cho+Cr and Lac/NAA in the region 5 and 7 days after infarction (P<0.05), and significantly increased the ratios of bATP/PME+PDE and bATP/PCr in the whole brain 1 day after infarction (P<0.05). The results indicated that the infracted region had severe edema, increased Lac and apparent neuronal dysfunction and death, and energy metabolism of the whole brain decreased after focal infarction, and that batroxobin effectively ameliorated the above-mentioned abnormal changes.

  4. Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

    Science.gov (United States)

    Latorre, Julius Gene S; Schmidt, Elena B

    2015-09-01

    No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids. These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions. Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation. The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke.

  5. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M. (Univ. of Michigan, Ann Arbor (USA))

    1990-08-01

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung.

  6. Increased Levels of Sphingosylphosphorylcholine (SPC in Plasma of Metabolic Syndrome Patients.

    Directory of Open Access Journals (Sweden)

    Nahed El-Najjar

    Full Text Available Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163. Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.

  7. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients.

    Science.gov (United States)

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.

  8. 2030例急性脑梗死患者合并代谢综合征临床特点分析%2030 patients with acute cerebral infarction complicating metabolic syndrome: a clinical characteristic analysis

    Institute of Scientific and Technical Information of China (English)

    王栋梁; 李新; 王纪佐

    2010-01-01

    Objective To observe the levels of serum lipid, blood pressure, waist circumference and blood glucose and to investigate the clinical features of metabolic syndrome in patients with acute cerebral infarction. Methods Serum lipid, blood pressure (systolic/diastolic blood pressure), waist circumference, and blood glucose in 2030 patients with acute cerebral infarction were analyzed retrospectively. Results The prevalence of metabolic syndrome of 2030 inpatients with acute cerebral infarction was 67.73%, and the men and women were 71.80% and 62.00% respectively. The proportions of hypertension, abnormal waist circumference, lipid abnormalities, and impaired fasting glucose in the men were significantly higher than those in the women (all P < 0.05 ). The proportions of metabolic syndrome,hypertension, abnormal waist circumference, and impaired fasting glucose increase with the age (all P < 0.05 ). Conclusions The prevalence of metabolic syndrome in patients with acute cerebral infarction is high. It is very important to evaluate metabolic syndrome in patients with acute cerebral infarction. Controlling dyslipidemia, hypertension, hyperglycosemia, and obesity in the primary and secondary prevention of ischemic stroke can not be ignored.%目的 观察急性脑梗死患者血脂、血压、腰围和空腹血糖水平,并探讨其代谢综合征的临床特点.方法 回顾性分析2030例急性脑梗死患者的血脂、血压(收缩压、舒张压)、腰围和空腹血糖水平.结果 2030例急性脑梗死住院患者的代谢综合征患病率为67.73%,男性为71.80%,显著高于女性的62.00%(P<0.001).男性患者高血压、腰围异常、血脂异常和窄腹血糖受损比例均显著高于女性(P<0.005).代谢综合征以及高血压、腰围异常、血脂异常和空腹血糖受损比例随年龄增大而增高(P<0.05).结论 脑梗死患者的代谢综合征患病率很高.对脑梗死患者进行代谢综合征评价非常重要,控制血脂异

  9. Increased eosinophil activity in acute Plasmodium falciparum infection - association with cerebral malaria

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Reimert, C M; Tette, E

    1998-01-01

    followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM...

  10. Increasing metabolic rate despite declining body weight in an adult parasitoid wasp.

    Science.gov (United States)

    Casas, Jérôme; Body, Mélanie; Gutzwiller, Florence; Giron, David; Lazzari, Claudio R; Pincebourde, Sylvain; Richard, Romain; Llandres, Ana L

    2015-08-01

    Metabolic rate is a positive function of body weight, a rule valid for most organisms and the basis of several theories of metabolic ecology. For adult insects, however, the diversity of relationships between body mass and respiration remains unexplained. The aim of this study is to relate the respiratory metabolism of a parasitoid with body weight and foraging activity. We compared the metabolic rate of groups of starving and host-fed females of the parasitoid Eupelmus vuilleti recorded with respirometry for 7days, corresponding to the mean lifetime of starving females and over half of the lifetime of foraging females. The dynamics of carbohydrate, lipid and protein in the body of foraging females were quantified with biochemical techniques. Body mass and all body nutrients declined sharply from the first day onwards. By contrast, the CO2 produced and the O2 consumed increased steadily. Starving females showed the opposite trend, identifying foraging as the reason for the respiration increase of feeding females. Two complementary physiological processes explain the unexpected relationship between increasing metabolic rate and declining body weight. First, host hemolymph is a highly unbalanced food, and the excess nutrients (protein and carbohydrate) need to be voided, partially through excretion and partially through respiration. Second, a foraging young female produces eggs at an increasing rate during the first half of its lifetime, a process that also increases respiration. We posit that the time-varying metabolic rate contributions of the feeding and reproductive processes supplements the contribution of the structural mass and lead to the observed trend. We extend our explanations to other insect groups and discuss the potential for unification using Dynamic Energy Budget theory.

  11. Fructose increases corticosterone production in association with NADPH metabolism alterations in rat epididymal white adipose tissue.

    Science.gov (United States)

    Prince, Paula D; Santander, Yanina A; Gerez, Estefania M; Höcht, Christian; Polizio, Ariel H; Mayer, Marcos A; Taira, Carlos A; Fraga, Cesar G; Galleano, Monica; Carranza, Andrea

    2017-08-01

    Metabolic syndrome is an array of closely metabolic disorders that includes glucose intolerance/insulin resistance, central obesity, dyslipidemia, and hypertension. Fructose, a highly lipogenic sugar, has profound metabolic effects in adipose tissue, and has been associated with the etiopathology of many components of the metabolic syndrome. In adipocytes, the enzyme 11 β-HSD1 amplifies local glucocorticoid production, being a key player in the pathogenesis of central obesity and metabolic syndrome. 11 β-HSD1 reductase activity is dependent on NADPH, a cofactor generated by H6PD inside the endoplasmic reticulum. Our focus was to explore the effect of fructose overload on epididymal white adipose tissue (EWAT) machinery involved in glucocorticoid production and NADPH and oxidants metabolism. Male Sprague-Dawley rats fed with a fructose solution (10% (w/v) in tap water) during 9 weeks developed some characteristic features of metabolic syndrome, such as hypertriglyceridemia, and hypertension. In addition, high levels of plasma and EWAT corticosterone were detected. Activities and expressions of H6PD and 11 β-HSD1, NAPDH content, superoxide anion production, expression of NADPH oxidase 2 subunits, and indicators of oxidative metabolism were measured. Fructose overloaded rats showed an increased potential in oxidant production respect to control rats. In parallel, in EWAT from fructose overloaded rats we found higher expression/activity of H6PD and 11 β-HSD1, and NADPH/NADP(+) ratio. Our in vivo results support that fructose overload installs in EWAT conditions favoring glucocorticoid production through higher H6PD expression/activity supplying NADPH for enhanced 11 β-HSD1 expression/activity, becoming this tissue a potential extra-adrenal source of corticosterone under these experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

    Science.gov (United States)

    Jeong, Jeong-Won; Asano, Eishi; Kumar Pilli, Vinod; Nakai, Yasuo; Chugani, Harry T; Juhász, Csaba

    2017-03-21

    To determine the spatial relationship between 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp, 2017. © 2017

  13. Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    Science.gov (United States)

    Hashimoto, Michio; Inoue, Takayuki; Katakura, Masanori; Tanabe, Yoko; Hossain, Shahdat; Tsuchikura, Satoru; Shido, Osamu

    2013-10-01

    Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

  14. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena;

    2008-01-01

    with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...... expression in brain tissue was measured by real time PCR. RESULTS: Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect...

  15. Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; McKay, V; Morris-Jones, S D

    1994-01-01

    receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured...... concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We...

  16. Lateralized increases in cerebral blood flow during performance of verbal and spatial tasks: relationship with performance level.

    Science.gov (United States)

    Gur, R C; Ragland, J D; Resnick, S M; Skolnick, B E; Jaggi, J; Muenz, L; Gur, R E

    1994-03-01

    Physiologic neuroimaging studies have shown lateralized regional increase in brain activity during cognitive tasks, but the hypothesis that such changes are correlated with task performance has not been tested directly. We examined cerebral blood flow (CBF) changes induced by cognitive tasks in relation to performance. CBF was measured with the 133Xenon clearance method in 34 normal right-handed young (age verbal analogies and a spatial line orientation test. Performance measures included "speed" and "power" estimates of both activation tasks. Resting CBF was moderately correlated with performance. The correlations were slightly higher with activated CBF for verbal but not spatial performance. The degree of increase (task-baseline) did not correlate with performance for either task. The highest and topographically specific correlations were obtained between laterality of CBF and verbal performance. Higher left hemispheric activation was correlated with verbal performance, and this correlation was significantly higher in the angular gyrus region. For the spatial task the correlations were with relatively higher right hemispheric activation but without regional specificity. The results underscore the importance of integrating behavioral performance data with physiologic measures in neuroimaging activation studies.

  17. Increased sensitivity to ET-1 in rat cerebral arteries following organ culture

    DEFF Research Database (Denmark)

    Hansen-Schwartz, J; Edvinsson, L

    2000-01-01

    Endothelin-1 (ET-1) is recognized as being involved in the pathophysiology of cerebrovascular diseases. Using organ culture as a model for possible pathological changes we studied changes in ET(A) and ETB receptor function using a sensitive in vitro method. We observed an up-regulation of the ET......(B) receptor and an amazingly increased sensitivity to ET-1 by 3 log units in pEC50; pEC50(fresh) was 8.7 +/- 0.1, and pEC50(cultured) was 11.7 +/- 0.3. pA2 for FR139317 in the fresh vessel was 7.0 +/- 0.2 whereas it could not be obtained for the cultured vessel, indicating a possible cross-talk between the ET......(A) and ET(B) receptors. The increased sensitivity to ET-1 could also take place during cerebrovascular disease such as stroke or haemorrhage rendering the vessels considerably more sensitive to ET-1....

  18. Comparable cerebral oxygenation patterns in younger and older adults during dual-task walking with increasing load

    Directory of Open Access Journals (Sweden)

    Sarah A. Fraser

    2016-10-01

    Full Text Available The neuroimaging literature on dual-task gait clearly demonstrates increased prefrontal cortex (PFC involvement when performing a cognitive task while walking. However, findings from direct comparisons of the cerebral oxygenation patterns of younger (YA and older (OA adults during dual-task walking are mixed and it is unclear how YA and OA respond to increasing cognitive load (difficulty while walking. This functional near infra-red (fNIRS study examined cerebral oxygenation of YA and OA during self-paced dual-task treadmill walking at two different levels of cognitive load (auditory n-back. Changes in accuracy (% as well as oxygenated (HbO and deoxygenated (HbR hemoglobin were examined. For the HbO and HbR measures, eight regions of interest (ROIs were assessed: the anterior and posterior dorsolateral and ventrolateral PFC (aDLPFC, pDLPFC, aVLPFC, pVLPFC in each hemisphere. Nineteen YA (M = 21.83 yrs and 14 OA (M = 66.85 yrs walked at a self-selected pace while performing auditory 1-back and 2-back tasks. Walking alone (single motor: SM and performing the cognitive tasks alone (single cognitive: SC were compared to dual-task walking (DT = SM + SC. In the behavioural data, participants were more accurate in the lowest level of load (1-back compared to the highest (2-back; p ˂ .001. YA were more accurate than OA overall (p = .009, and particularly in the 2-back task (p = .048. In the fNIRS data, both younger and older adults had task effects (SM < DT in specific ROIs for ∆HbO (3 YA, 1 OA and ∆HbR (7 YA, 8 OA. After controlling for walk speed differences, direct comparisons between YA and OA did not reveal significant age differences, but did reveal a difficulty effect in HbO in the left aDLPFC (p = .028 and significant task effects (SM < DT in HbR for 6 of the 8 ROIs. Findings suggest that YA and OA respond similarly to manipulations of cognitive load when walking on a treadmill at a self-selected pace.

  19. Analyzing Ph value, energy and phospholipid metabolism of various cerebral tumors and normal brain tissue with 31P magnetic resonance spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Wei Tan; Guangyao Wu; Junmo Sun

    2006-01-01

    BACKGROUND: 31P magnetic resonance spectroscopy (31P MRS) can be used to non-injuredly and dynamicly detect various metabolites including phosphorus in organis and reflect changes of phospholipid metabolism and energy metabolism in tissue and pH value in cells.OBJECTIVE: To observe changes of pH value, phospholipid metabolism and energy metabolism of various cerebral tumors and normal brain tissue with 31P MRS.DESIGN: Semi-quantitative contrast observation.PARTICIPANTS: A total of 44 patients with cerebral tumor diagnosed with surgery operation were selected from the Department of Magnetic Resonance, Central South Hospital, Wuhan University from September 2004 to June 2006. All the subjects had complete 31P MRS data before steroid and operation. Among them,16 patients had glioma of grade Ⅱ-Ⅲ, 12 spongioblastoma and 16 meningioma. The mean age was (45±6)years. Another 36 subjects without focus on cerebral MRI were regarded as normal group, including 19 males and 18 females, and the mean age was (41±4) years. Included subjects were consent.METHODS: Eclipse1.5T MRS (Philips Company) was used to collect wave spectrum; jMRUI(1.3) was used to analyze experimental data and calculate pH value in voxel and ratios of phosphocreatine (PCr)/inorganic phosphate (Pi), PCr/phosphodiesterase (PDE) and phosphomonoesterase (PME)/β-adenosine triphosphate (β-ATP) of various metabolites. 31P MRS results were compared with t test between tumor patients and normal subjects.MAIN OUTCOME MEASURES: Changes of phospholipid metabolism (PME/PDE), energy metabolism (PCr/ATP) and pH value of various cerebral tumors and normal brain tissues.RESULTS: A total of 44 cases with cerebral tumor and 36 normal subjects were involved in the final analysis. pH value and semi-quantitative measurements of normal brain tissues and various cerebral tumors: ① pH value at top occipital region and temple occipital region of normal brain tissue was 7.04±0.02;PCt/β-ATP was 1.51 ±0.03; PCt/Pi was 2.85

  20. The increase in the number of astrocytes in the total cerebral ischemia model in rats

    Science.gov (United States)

    Kudabayeva, M.; Kisel, A.; Chernysheva, G.; Smol'yakova, V.; Plotnikov, M.; Khodanovich, M.

    2017-08-01

    Astrocytes are the most abundant cell class in the CNS. Astrocytic therapies have a huge potential for neuronal repair after stroke. The majority of brain stroke studies address the damage to neurons. Modern studies turn to the usage of morphological and functional changes in astroglial cells after stroke in regenerative medicine. Our study is focused on the changes in the number of astrocytes in the hippocampus (where new glia cells divide) after brain ischemia. Ischemia was modeled by occlusion of tr. brachiocephalicus, a. subclavia sin., a. carotis communis sin. Astrocytes were determined using immunohistochemical labeling with anti GFAP antibody. We found out that the number of astrocytes increased on the 10th and 30th days after stroke in the CA1, CA2 fields, the granular layer of dentate gyrus (GrDG) and hilus. The morphology of astrocytes became reactive in these regions. Therefore, our results revealed long-term reactive astrogliosis in the hippocampus region after total ischemia in rats.

  1. BH4 treatment in BH4-responsive PKU patients : Preliminary data on blood prolactin concentrations suggest increased cerebral dopamine concentrations

    NARCIS (Netherlands)

    van Vliet, Danique; Anjema, Karen; Jahja, Rianne; de Groot, Martijn J; Liemburg, Geertje B; Heiner-Fokkema, Rebecca; van der Zee, Eddy A; Derks, Terry G J; Kema, Ido P; van Spronsen, Francjan J

    2015-01-01

    In phenylketonuria (PKU), cerebral neurotransmitter deficiencies have been suggested to contribute to brain dysfunction. Present treatment aims to reduce blood phenylalanine concentrations by a phenylalanine-restricted diet, while in some patients blood phenylalanine concentrations also respond to c

  2. Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Pelligrino, D A; Paulson, O B;

    1994-01-01

    The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF...

  3. Nitric oxide (NO) is an endogenous anticonvulsant but not a mediator of the increase in cerebral blood flow accompanying bicuculline-induced seizures in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Theard, M A; Pelligrino, D A;

    1994-01-01

    ) is NO an endogenous anticonvulsant or proconvulsant substance? and (2) is the cerebral blood flow (CBF) increase accompanying bicuculline (BC)-induced seizures mediated by NO? The experiments were performed in 300-400-g Wistar rats anesthetized with 0.6% halothane and 70% N2O/30% O2. CBF was measured using...

  4. Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Martina Svensson

    2016-12-01

    Full Text Available Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to study the effects of 4.5 weeks of forced treadmill running prior to ischemia on neuronal damage, neuroinflammation and its effect on general stress by measuring corticosterone in feces. We subjected C57bl/6 mice (n = 63 to either treadmill running or a sedentary program prior to induction of global ischemia. Anxious, depressive, and cognitive behaviors were analyzed. Stress levels were analyzed using a corticosterone ELISA. Inflammatory and neurological outcomes were analyzed using immunohistochemistry, multiplex electrochemoluminescence ELISA and Western blot. To our surprise, we found that forced treadmill running induced a stress response, with increased anxiety in the Open Field test and increased levels of corticosterone. In accordance, mice subjected to forced exercise prior to ischemia developed larger neuronal damage in the hippocampus and showed higher cytokine levels in the brain and blood compared to non-exercised mice. The extent of neuronal damage correlated with increased corticosterone levels. To compare forced treadmill with voluntary wheel running, we used a different set of mice that exercised freely on running wheels. These mice did not show any anxiety or increased corticosterone levels. Altogether, our results indicate that exercise pre-conditioning may not be beneficial if the animals are forced to run as it can induce a detrimental stress response.

  5. Metabolic changes of prefrontal cerebral lobe ,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

    Institute of Scientific and Technical Information of China (English)

    Qinggang Xu; Hong Cao; Qingwei Song; Jianlin Wu

    2008-01-01

    BACKGROUND:Proton magnetic resonance spectroscopy(1H-MRS)non-invasively detects changes in chemical substances in the brain,which reflects the pathological metabolism.OBJECTIVE:To investigate changes in N-acetyl-aspartate(NAA),choline(Cho),creatine(Cr),and myoinositol(MI)in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression(PSD)using 1H-MRS.DESIGN:A case control study.SETTING:The First Affiliated Hospital of the Dalian Medical University.PARTICIPANTS:A total of 38 patients with stroke(28 male and 10 female patients,aged 40 to 79 years)were selected from the Department of Neurology,1st Atfiliated Hospital,Dalian Medical University,from February to October in 2004.All subjects met the DSM-IV criteria for cerebrovascular disease and depression.The degree of depression was defined according to Hamilton criteria.38 patients with PSD were divided into two groups according to the time after ischemia,20 patients in the acute group with less than 10 days after ischemic attack(mild:16 patients,moderate/severe:4 patients)and 18 patients in the chronic group with more than 11 days after ischemic attack(mild:15 patients,moderate/severe:3 patients).Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group.The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht,and each participant signed an informed consent form.METHODS:Spectra were acquired by multi-voxel point-resolved spectroscopy(PRESS)sequence with GE signal.ST MP-di,localized in prefrontal cerebral lobe and cerebellum.Values of NAA,Cho,MI,and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS11.5.MAIN OUTCOME MEASURES:Metabolite concentration in different brain regions of interest.Difference in metabolites between distinctly graded PSD patients and control subjects.Exclusion of age

  6. Metabolic flux phenotype of tobacco hairy roots engineered for increased geraniol production

    NARCIS (Netherlands)

    Masakapalli, S.K.; Ritala, A.; Dong, L.M.; Krol, van der A.R.; Oksman-Caldentey, K.M.; Ratcliffe, R.G.; Sweetlove, L.J.

    2014-01-01

    The goal of this study was to characterise the metabolic flux phenotype of transgenic tobacco (Nicotiana tabacum) hairy roots engineered for increased biosynthesis of geraniol, an intermediate of the terpenoid indole alkaloid pathway. Steady state, stable isotope labelling was used to determine flux

  7. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    OpenAIRE

    Schilling Brian K; Hammond Kelley G; Fisher-Wellman Kelsey H; Bloomer Richard J; Weber Adrianna A; Cole Bradford J

    2009-01-01

    Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  8. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    Directory of Open Access Journals (Sweden)

    Schilling Brian K

    2009-04-01

    Full Text Available Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  9. Increased metabolic turnover rate and transcapillary escape rate of albumin in long-term juvenile diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, N; Sander, E

    1975-01-01

    smaller than 0.05). The previously reported decrease in the intravascular albumin mass in long-term diabetics was thus confirmed by an average of 59.0 g/m2 surface area, compared with a normal value of 71.7 g/m2-(minus18%) (P smaller than 0.005). The albumin metabolic rate was increased, the fractional...

  10. Respirometry increases cortisol levels in rainbow trout Oncorhynchus mykiss: implications for measurements of metabolic rate

    DEFF Research Database (Denmark)

    Murray, L.; Rennie, M. D.; Svendsen, Jon Christian

    2017-01-01

    This study aimed to assess the extent to which chasing, handling and confining Oncorhynchus mykiss to a small respirometer chamber during respirometric experiments is stressful and affects metabolic measurements. The study observed increased cortisol levels in animals tested using a chase protocol...... and subsequent intermittent-flow respirometry, suggesting that this procedural treatment may stress animals...

  11. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities

    DEFF Research Database (Denmark)

    Høgh, P; Garde, Ellen; Mortensen, Erik Lykke;

    2007-01-01

    OBJECTIVE: Apolipoprotein E-epsilon4 (APOE-epsilon4) is a potential risk factor for cerebral vascular disease. The aim of the present study was to examine the relative importance of APOE-epsilon4 and other relevant risk factors for the extent of cerebral white matter hyperintensity (WMH...... the relative importance of the potential risk factors. RESULTS: APOE genotype and antihypertensive treatment were significantly associated with severity of total WMH load (P epsilon4 and WMH. Pharmaceutical treatment for arterial...

  12. Effect of cerebral blood flow on consciousness and outcome after head injury. Assessment by jugular bulb venous metabolism and IMP-SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Imaizumi, Shigeki; Onuma, Takehide; Motohashi, Osamu; Kameyama, Motonobu; Ishii, Kiyoshi [Sendai City Hospital (Japan)

    2002-10-01

    This study was performed to elucidate the therapeutical value of arteriojugularvenous oxygen difference (AVDO{sub 2}) in the ultra-emergent period after head injury. Rational therapeutic strategy after severe head injury needs information concerning the dynamical change of cerebral blood flow (CBF) and metabolism. We monitored the cerebral venous metabolism within 6 hours after head injury until the day IMP-SPECT was performed. Whole brain cerebral blood flow detected by IMP-SPECT and AVDO{sub 2} at the same day was compared, which restored to the period within 6 hours after head injury. From this procedure, we could outline cerebral blood flow conditions by only AVDO{sub 2} without IMP-SPECT in the ultra-emergent period. Eighty-six patients with head injury who were carried to our emergency center in the period of recent 2 years aged ranging from 15 to 94 years were the subjects. They all performed jugular bulb cannulation within 6 hours after the accident (Martin's phase I: day 0) to know saturation of jugular vein (SjO{sub 2}), AVDO{sub 2} and AVL. They were monitored until the day IMP-SPECT was performed (Martin's phase II; day 1-3 or phase III; day 4-15). The correlation between CBF and AVDO{sub 2}. The effect of CBF and cerebral venous metabolism on consciousness and outcome was also analyzed. CBF and AVDO{sub 2} in phase II and III were reversely correlated (p<0.0001). Normal CBF corresponded with 5.0 vol% in AVDO{sub 2}. AVDO{sub 2} in all cases changed 6.2 vol% at phase I, 4.5 vol% at phase II and 5.1 vol% at phase III. Glasgow comascale (GCS) on admission under 8 (n=47) and over 9 (n=39) significantly differed in AVDO{sub 2} and CBF in the period of II and III. The patients with favorable consciousness showed low AVDO{sub 2} and hyperemia afterwards. Dead cases in phase I (n=19) showed high AVDO{sub 2} and low SjO{sub 2}. The patients with severe disability (SD) (n=13) showed high AVDO{sub 2} and low CBF and the patients with good recovery (GR

  13. Extracellular brain pH with or without hypoxia is a marker of profound metabolic derangement and increased mortality after traumatic brain injury

    Science.gov (United States)

    Timofeev, Ivan; Nortje, Jurgens; Al-Rawi, Pippa G; Hutchinson, Peter JA; Gupta, Arun K

    2013-01-01

    Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pHbt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pHbt and PbtO2: 1—low PbtO2/pHbt, 2—low pHbt/normal PbtO2, 3—normal pHbt/low PbtO2, and 4—normal pHbt/PbtO2). Microdialysis values were compared between the groups. The relationship between PbtO2 and lactate/pyruvate (LP) ratio was evaluated at different pHbt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1—higher LP and reduced glucose (P<0.001). A significant negative correlation between LP and PbtO2 (rho=−0.159, P<0.001) was stronger at low pHbt (rho=−0.201, P<0.001) and nonsignificant at normal pHbt (P=0.993). The state 2 was a significant discriminator of mortality categories (P=0.031). Decreased pHbt is associated with impaired metabolism. Measuring pHbt with PbtO2 is a more robust way of detecting metabolic derangements. PMID:23232949

  14. A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe.

    Science.gov (United States)

    Vaughan, O R; Davies, K L; Ward, J W; de Blasio, M J; Fowden, A L

    2016-11-01

    Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta. The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta. In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity. Concomitantly, the uteroplacental tissues produced lactate at a greater rate. The results show that maternal cortisol concentrations regulate uteroplacental glycolytic metabolism, producing lactate for use in utero. Prolonged increases in placental lactate production induced by cortisol overexposure may contribute to the adverse effects of maternal stress on fetal wellbeing. Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg(-1)  day(-1) i.v. for 5 days, n = 20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day ∼130 of pregnancy (term = 145 days). Compared to saline infusion (n = 21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P Cortisol infusion also raised maternal insulin, glucose and lactate concentrations, and blood pH, PCO2 and HCO3(-) concentration. Although total uterine glucose uptake determined by Fick's principle was unaffected, a greater proportion was consumed by the uteroplacental tissues, so net fetal glucose uptake was 29% lower in cortisol-infused than control ewes (P  2-fold greater in cortisol- than

  15. Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases Coordination between Irregular Cerebral and Cardiac Activities.

    Science.gov (United States)

    Sik, Hin Hung; Gao, Junling; Fan, Jicong; Wu, Bonnie Wai Yan; Leung, Hang Kin; Hung, Yeung Sam

    2017-05-10

    In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities.

  16. Kinetic and metabolic considerations in the use of (I-125) HIPDM as a tracer for quantitative measurement of regional cerebral blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Lucignani, G.; Nehlig, A.; Blasberg, R.; Patlak, C.S.; Anderson, L.; Kung, H.F.; Fieschi, C.; Fazio, F.; Sokoloff, L.

    1984-01-01

    The kinetics of cerebral uptake and the metabolism of radioactive iodine labeled HIPDM (N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-(I-125)iodobenzyl) -1,3-propanediamine)(I-125)HIPDM were studied in vivo in male adult Sprague-Dawley rats in order to evaluate the potential usefulness of this compound for quantitative measurement of regional cerebral blood flow (rCBF). The first pass extraction fraction of (I-125)HIPDM in brain was found to be about 80%. The arterial concentration of unmetabolized (I-125)HIPDM following an i.v. pulse drops rapidly and represents only 30% of the blood sample total radioactivity at 60 minutes, whereas 92% of the radioactivity in brain tissue at the same time is in unaltered (I-125)HIPDM. The rate constant for (I-125)HIPDM transport across the blood-brain barrier (BBB) was calculated on the basis of a distribution model in which bi-directional exchange of the tracer between brain tissue and vascular space is assumed. A kinetic model and an operational equation have been derived for determination of rCBF with this molecule. The model and equation take into account the three following factors: (a) incomplete first pass extraction; (b) HIPDM metabolism; (c) bi-directional flux of tracer across the BBB. The observations suggest that this molecule might be of potential usefulness for rCBF measurements with single photon emission tomography, provided that all these factors are evaluated in man.

  17. Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI.

    Science.gov (United States)

    Ances, Beau M; Leontiev, Oleg; Perthen, Joanna E; Liang, Christine; Lansing, Amy E; Buxton, Richard B

    2008-02-15

    Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.

  18. Improved light collection and wavelet de-noising enable quantification of cerebral blood flow and oxygen metabolism by a low-cost, off-the-shelf spectrometer

    Science.gov (United States)

    Diop, Mamadou; Wright, Eric; Toronov, Vladislav; Lee, Ting-Yim; St. Lawrence, Keith

    2014-05-01

    Broadband continuous-wave near-infrared spectroscopy (CW-NIRS) is an attractive alternative to time-resolved and frequency-domain techniques for quantifying cerebral blood flow (CBF) and oxygen metabolism in newborns. However, efficient light collection is critical to broadband CW-NIRS since only a small fraction of the injected light emerges from any given area of the scalp. Light collection is typically improved by optimizing the contact area between the detection system and the skin by means of light guides with large detection surface. Since the form-factor of these light guides do not match the entrance of commercial spectrometers, which are usually equipped with a narrow slit to improve their spectral resolution, broadband NIRS spectrometers are typically custom-built. Nonetheless, off-the-shelf spectrometers have attractive advantages compared to custom-made units, such as low cost, small footprint, and wide availability. We demonstrate that off-the-shelf spectrometers can be easily converted into suitable instruments for deep tissue spectroscopy by improving light collection, while maintaining good spectral resolution, and reducing measurement noise. The ability of this approach to provide reliable cerebral hemodynamics was illustrated in a piglet by measuring CBF and oxygen metabolism under different anesthetic regimens.

  19. A randomized controlled trial of web-based training to increase activity in children with cerebral palsy.

    Science.gov (United States)

    Mitchell, Louise E; Ziviani, Jenny; Boyd, Roslyn N

    2016-07-01

    To determine the efficacy of web-based training on activity capacity and performance in children with unilateral cerebral palsy (CP). In a matched-pairs randomized waitlist controlled trial, independently ambulant children and adolescents with unilateral CP were allocated to receive 30 minutes of training (intervention) 6 days per week, or usual care (waitlist control) for 20 weeks. Activity capacity was assessed using maximal repetitions of functional strength tasks and 6-minute walk test (6MWT); performance using 4-day ActiGraph GT3X+ accelerometer records at baseline and 20 weeks. Data were analysed by intention to treat comparing between groups using hierarchical linear modelling. Participants were n=101, 52 males, mean age 11 years 3 months (SD 2y 4mo). Intervention participants completed a mean 32.4 hours (SD 17.2) of training, associated with significant improvements in functional strength (mean difference 19.3 repetitions; 95% confidence interval [CI] 10.8-27.7; p0.05). Training was effective at increasing functional strength and walking endurance in independently ambulant children with unilateral CP. This did not translate into improvements in activity performance. © 2016 Mac Keith Press.

  20. Facilitation handlings induce increase in electromyographic activity of muscles involved in head control of cerebral palsy children.

    Science.gov (United States)

    Simon, Anelise de Saldanha; do Pinho, Alexandre Severo; Grazziotin Dos Santos, Camila; Pagnussat, Aline de Souza

    2014-10-01

    This study aimed to investigate the electromyographic (EMG) activation of the main cervical muscles involved in the head control during two postures widely used for the facilitation of head control in children with Cerebral Palsy (CP). A crossover trial involving 31 children with clinical diagnosis of CP and spastic quadriplegia was conducted. Electromyography was used to measure muscular activity in randomized postures. Three positions were at rest: (a) lateral decubitus, (b) ventral decubitus on the floor and (c) ventral decubitus on the wedge. Handlings for facilitating the head control were performed using the hip joint as key point of control in two postures: (a) lateral decubitus and (b) ventral decubitus on wedge. All children underwent standardized handlings, performed by the same researcher with experience in the neurodevelopmental treatment. EMG signal was recorded from muscles involved in the head control (paraspinal and sternocleidomastoid muscles) in sagittal, frontal and transverse planes, at the fourth cervical vertebra (C4), tenth thoracic vertebra (T10) and sternocleidomastoid muscle (SCM) levels. The results showed a significant increase in muscle activation when handling was performed in the lateral decubitus at C4 (Pcontrol, as evaluated by the activity of cervical and upper trunk muscles. Handling performed in lateral decubitus may induce a slightly better facilitation of head control. These findings contribute to evidence-based physiotherapy practice for the rehabilitation of severely spastic quadriplegic CP children.

  1. Erythropoietin Levels Increase during Cerebral Malaria and Correlate with Heme, Interleukin-10 and Tumor Necrosis Factor-Alpha in India.

    Science.gov (United States)

    Dalko, Esther; Tchitchek, Nicolas; Pays, Laurent; Herbert, Fabien; Cazenave, Pierre-André; Ravindran, Balachandran; Sharma, Shobhona; Nataf, Serge; Das, Bidyut; Pied, Sylviane

    2016-01-01

    Cerebral malaria (CM) caused by Plasmodium falciparum parasites often leads to the death of infected patients or to persisting neurological sequelae despite anti-parasitic treatments. Erythropoietin (EPO) was recently suggested as a potential adjunctive treatment for CM. However diverging results were obtained in patients from Sub-Saharan countries infected with P. falciparum. In this study, we measured EPO levels in the plasma of well-defined groups of P. falciparum-infected patients, from the state of Odisha in India, with mild malaria (MM), CM, or severe non-CM (NCM). EPO levels were then correlated with biological parameters, including parasite biomass, heme, tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon gamma-induced protein (IP)-10, and monocyte chemoattractant protein (MCP)-1 plasma concentrations by Spearman's rank and multiple correlation analyses. We found a significant increase in EPO levels with malaria severity degree, and more specifically during fatal CM. In addition, EPO levels were also found correlated positively with heme, TNF-α, IL-10, IP-10 and MCP-1 during CM. We also found a significant multivariate correlation between EPO, TNF-α, IL-10, IP-10 MCP-1 and heme, suggesting an association of EPO with a network of immune factors in CM patients. The contradictory levels of circulating EPO reported in CM patients in India when compared to Africa highlights the need for the optimization of adjunctive treatments according to the targeted population.

  2. Increased metabolic activity of neutrophils in patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    Vaidyanathan, Ashwin; Damodar, Komaladevi Sampath

    2015-01-01

    Aims: To compare the metabolic activity of peripheral neutrophils in patients diagnosed with chronic obstructive pulmonary disease (COPD) with that of healthy, nonsmoking volunteers. Materials and Methods: Venous blood samples were taken from patients diagnosed with COPD as well as from healthy nonsmokers. Each sample was subjected to the nitro blue tetrazolium (NBT) test in which neutrophils exhibiting elevated metabolic activity were detected by light microscopy. The test was repeated after stimulation with Escherichia coli (E. coli) endotoxin with fresh samples. Neutrophils showing dye uptake were then counted in each case. Results: We found that the mean numbers of activated neutrophils without and with the addition of endotoxin were 19% and 23%, respectively, in the control group and 56% and 62%, respectively, in the test group. Two-sample t-test statistic revealed that there was a significant (P < 0.01) increase in neutrophilic metabolic activity in patients with COPD as compared to that in healthy volunteers. This significance remained even after stimulation using E. coli endotoxin. Conclusion: The results hint at a potentially relevant pathogenic mechanism in COPD related to the metabolic activity of neutrophils. By exhibiting enhanced metabolic activity, neutrophils in the COPD patients are more likely to be involved in damaging lung tissues. PMID:26664165

  3. Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.

    Science.gov (United States)

    Frederick, David W; Davis, James G; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A; Nakamaru-Ogiso, Eiko; Baur, Joseph A

    2015-01-16

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.

  4. Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta-Analysis

    Science.gov (United States)

    Wang, Huajun; Cheng, Yanmei; Shao, Decheng; Chen, Junyuan; Sang, Yuan; Gui, Tao; Luo, Simin; Li, Jieruo; Chen, Chao; Ye, Yongguang; Yang, Yong; Li, Yikai

    2016-01-01

    Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38–3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03–1.07, p < 0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.

  5. 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.

  6. Strategies for improving the Voxel-based statistical analysis for animal PET studies: assessment of cerebral glucose metabolism in cat deafness model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Kang, Hye Jin; Im, Ki Chun; Moon, Dae Hyuk; Lim, Sang Moo; Oh, Seung Ha; Lee, Dong Soo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In imaging studies of the human brain, voxel-based statistical analysis method was widely used, since these methods were originally developed for the analysis of the human brain data, they are not optimal for the animal brain data. The aim of this study is to optimize the procedures for the 3D voxel-based statistical analysis of cat FDG PET brain images. A microPET Focus 120 scanner was used. Eight cats underwent FDG PET scans twice before and after inducing the deafness. Only the brain and adjacent regions were extracted from each data set by manual masking. Individual PET image at normal and deaf state was realigned to each other to remove the confounding effects by the different spatial normalization parameters on the results of statistical analyses. Distance between the sampling points on the reference image and kernel size of Gaussian filter applied to the images before estimating the realignment parameters were adjusted to 0.5 mm and 2 mm. Both data was then spatial normalized onto study-specific cat brain template. Spatially normalized PET data were smoothed and voxel-based paired t-test was performed. Cerebral glucose metabolism decreased significantly after the loss of hearing capability in parietal lobes, postcentral gyri, STG, MTG, lTG, and IC at both hemisphere and left SC (FDR corrected P < 0.05, k=50). Cerebral glucose metabolism in deaf cats was found to be significantly higher than in controls in the right cingulate (FDR corrected P < 0.05, k=50). The ROI analysis also showed significant reduction of glucose metabolism in the same areas as in the SPM analysis, except for some regions (P < 0.05). Method for the voxel-based analysis of cat brain PET data was optimized for analysis of cat brain PET. This result was also confirmed by ROI analysis. The results obtained demonstrated the high localization accuracy and specificity of the developed method, and were found to be useful for examining cerebral glucose metabolism in a cat cortical deafness model.

  7. Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

    Directory of Open Access Journals (Sweden)

    Valeska Lizzi Lagranha

    Full Text Available We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits, AMPA (GluR2 subunit and kainate (GluR6 subunit, as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT and glutaryl-CoA dehydrogenase deficient (Gchh-/- mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

  8. Adolescent Metabolic Syndrome Risk Is Increased with Higher Infancy Weight Gain and Decreased with Longer Breast Feeding

    OpenAIRE

    Kim Khuc; Estela Blanco; Raquel Burrows; Marcela Reyes; Marcela Castillo; Betsy Lozoff; Sheila Gahagan

    2012-01-01

    Background. Prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide. Meeting the criteria for the metabolic syndrome puts children at risk for later cardiovascular and metabolic disease. Methods. Using linear regression, we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year-old Chilean adolescents (n = 357), accounting for the extent of breastfeeding in infancy and known covariates in...

  9. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes.

    Directory of Open Access Journals (Sweden)

    Naoto Kudo

    Full Text Available Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT. Oxygen consumption (VO2 and energy expenditure (EE were increased significantly in mice treated with theaflavin rich fraction (TF compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes.

  10. Cerebral hemorrhage increases plasma concentrations of noradrenalin and creatine kinase MB fraction with induction of cardiomyocyte damage in rats.

    Science.gov (United States)

    Liang, Xiao-Min; Chen, Jia; Zhang, Tao; Liu, Juan; Jiang, Xiao-Jiang; Xu, Zhi-Qiang

    2014-12-01

    The incidence of cardiac damage is high during acute cerebral hemorrhage. The animal data on the relationship between cerebral apoplexy and cardiac damage are lacking. Thus, the aim of the study was to evaluate the effects of cerebral hemorrhage on plasma concentrations of monoamine transmitter noradrenalin (NA), creatine kinase muscle and brain (CK-MB) isoenzyme fraction, and cardiomyocyte changes in the rat model. In this study, 140 Wistar rats were randomly and equally divided into experimental and control groups, and collagenase was injected into the right caudate nucleus to induce cerebral hemorrhage in the experimental group. Plasma NA was analyzed using high-performance liquid chromatography with electrochemical detection and serum CK-MB was measured by enzyme reaction rate method. We found that both NA and CK-MB were elevated (p MB concentrations reached peak levels at 24 h which were found to be 3.52 ± 0.06 μg/L and 5.47 ± 0.49 μkat/L, respectively. Thereafter, NA and CK-MB concentrations decreased gradually. Plasma NA declined to the preoperative level (1.66 ± 0.03 μg/L) at 72 h, while CK-MB level (2.71 ± 0.17 μkat/L) was found to be still higher than its preoperative level. It was, therefore, concluded that plasma NA might be involved in the induction and development of cardiomyocytes damage during cerebral hemorrhage.

  11. Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.

    Science.gov (United States)

    Hansen, Fernanda; de Souza, Daniela Fraga; Silveira, Simone da Luz; Hoefel, Ana Lúcia; Fontoura, Júlia Bijoldo; Tramontina, Ana Carolina; Bobermin, Larissa Daniele; Leite, Marina Concli; Perry, Marcos Luiz Santos; Gonçalves, Carlos Alberto

    2012-12-01

    Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.

  12. Soil warming increases metabolic quotients of soil microorganisms without changes in temperature sensitivity of soil respiration

    Science.gov (United States)

    Marañón-Jiménez, Sara; Soong, Jenniffer L.; Leblans, Niki I. W.; Sigurdsson, Bjarni D.; Dauwe, Steven; Fransen, Erik; Janssens, Ivan A.

    2017-04-01

    Increasing temperatures can accelerate soil organic matter (SOM) decomposition and release large amounts of CO2 to the atmosphere, potentially inducing climate change feedbacks. Alterations to the temperature sensitivity and metabolic pathways of soil microorganisms in response to soil warming can play a key role in these soil carbon (C) losses. Here, we present results of an incubation experiment using soils from a geothermal gradient in Iceland that have been subjected to different intensities of soil warming (+0, +1, +3, +5, +10 and +20 °C above ambient) over seven years. We hypothesized that 7 years of soil warming would led to a depletion of labile organic substrates, with a subsequent decrease of the "apparent" temperature sensitivity of soil respiration. Associated to this C limitation and more sub-optimal conditions for microbial growth, we also hypothesized increased microbial metabolic quotients (soil respiration per unit of microbial biomass), which is associated with increases in the relative amount of C invested into catabolic pathways along the warming gradient. Soil respiration and basal respiration rates decreased with soil warming intensity, in parallel with a decline in soil C availability. Contrasting to our first hypothesis, we did not detect changes in the temperature sensitivity of soil respiration with soil warming or on the availability of nutrients and of labile C substrates at the time of incubation. However, in agreement to our second hypothesis, microbial metabolic quotients (soil respiration per unit of microbial biomass) increased at warmer temperatures, while the C retained in biomass decreased as substrate became limiting. Long-term (7 years) temperature increases thus triggered a change in the metabolic functioning of the soil microbial communities towards increasing energy costs for maintenance or resource acquisition, thereby lowering the capacity of C retention and stabilization of warmed soils. These results highlight the need

  13. Increased Expression of Slit2 and its Robo Receptors During Astroglial Scar Formation After Transient Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Jin, Xuyan; Shin, Yoo-Jin; Riew, Tae-Ryong; Choi, Jeong-Heon; Lee, Mun-Yong

    2016-12-01

    Slit2, a secreted glycoprotein, has recently been implicated in the post-ischemic astroglial reaction. The objective of this study was to investigate the temporal changes and cellular localization of Slit2 and its receptors, Robo1, Robo2, and Robo4, in a rat transient focal ischemia model induced by middle cerebral artery occlusion. We used double- and triple-immunolabeling to determine the cell-specific changes in Slit2 and its receptors during a 10-week post-ischemia period. The expression profiles of Slit2 and the Robo receptors shared overlapping expression patterns in sham-operated and ischemic striatum. Constitutive expression of Slit2 and Robo receptors was observed in striatal neurons with weak intensity, whereas in rats reperfused after ischemic insults, these immunoreactivities were increased in reactive astrocytes. Astroglial induction of Slit2 and Robo in the peri-infarct region was distinct on days 7-14 after reperfusion and thereafter increased progressively throughout the 10-week experimental period. Slit2 and Robo were prominently expressed in the perinuclear cytoplasm and main processes of reactive astrocytes forming the astroglial scar. This observation was confirmed by quantification of the mean fluorescence intensity of Slit2 and Robo receptors over reactive astrocytes localized at the edge of the infarct area. However, activated microglia/macrophages in the peri-infarct area were devoid of any specific labeling for Slit2 and Robo. Thus, our data revealed a selective and sustained induction of Slit2 and Robo in astrocytes localized throughout the astroglial scar after ischemic stroke, suggesting that Slit2/Robo signaling participates in glial scar formation and brain remodeling following ischemic injury.

  14. Brain structural connectivity increases concurrent with functional improvement: Evidence from diffusion tensor MRI in children with cerebral palsy during therapy

    Directory of Open Access Journals (Sweden)

    Zoë A. Englander

    2015-01-01

    Full Text Available Cerebral Palsy (CP refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005. Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17, who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

  15. 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

    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...

  16. 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

    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...

  17. Metabolic and respiratory costs of increasing song amplitude in zebra finches.

    Directory of Open Access Journals (Sweden)

    Sue Anne Zollinger

    Full Text Available Bird song is a widely used model in the study of animal communication and sexual selection, and several song features have been shown to reflect the quality of the singer. Recent studies have demonstrated that song amplitude may be an honest signal of current condition in males and that females prefer high amplitude songs. In addition, birds raise the amplitude of their songs to communicate in noisy environments. Although it is generally assumed that louder song should be more costly to produce, there has been little empirical evidence to support this assumption. We tested the assumption by measuring oxygen consumption and respiratory patterns in adult male zebra finches (Taeniopygia guttata singing at different amplitudes in different background noise conditions. As background noise levels increased, birds significantly increased the sound pressure level of their songs. We found that louder songs required significantly greater subsyringeal air sac pressure than quieter songs. Though increased pressure is probably achieved by increasing respiratory muscle activity, these increases did not correlate with measurable increases in oxygen consumption. In addition, we found that oxygen consumption increased in higher background noise, independent of singing behaviour. This observation supports previous research in mammals showing that high levels of environmental noise can induce physiological stress responses. While our study did not find that increasing vocal amplitude increased metabolic costs, further research is needed to determine whether there are other non-metabolic costs of singing louder or costs associated with chronic noise exposure.

  18. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork.

    Science.gov (United States)

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors.

  19. Increased isobutanol production in Saccharomyces cerevisiae by overexpression of genes in valine metabolism

    DEFF Research Database (Denmark)

    Chen, Xiao; Nielsen, Kristian Fog; Borodina, Irina;

    2011-01-01

    of its relative tolerance to alcohols, robustness in industrial fermentations, and the possibility for future combination of isobutanol production with fermentation of lignocellulosic materials. RESULTS: The yield of isobutanol was improved from 0.16 to 0.97 mg per g glucose by simultaneous...... overexpression of biosynthetic genes ILV2, ILV3, and ILV5 in valine metabolism in anaerobic fermentation of glucose in mineral medium in S. cerevisiae. Isobutanol yield was further improved by twofold by the additional overexpression of BAT2, encoding the cytoplasmic branched-chain amino-acid aminotransferase...... were 3.86 and 0.28 mg per g glucose, respectively. They increased to 4.12 and 2.4 mg per g glucose in yeast extract/peptone/dextrose (YPD) complex medium under aerobic conditions, respectively. CONCLUSIONS: Overexpression of genes ILV2, ILV3, ILV5, and BAT2 in valine metabolism led to an increase...

  20. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella

    DEFF Research Database (Denmark)

    Kovatcheva-Datchary, Petia; Nilsson, Anne; Akrami, Rozita

    2015-01-01

    The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day...... consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had...... increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non...

  1. Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice.

    Science.gov (United States)

    Temp, Fernanda Rossatto; Marafiga, Joseane Righes; Milanesi, Laura Hautrive; Duarte, Thiago; Rambo, Leonardo Magno; Pillat, Micheli Mainardi; Mello, Carlos Fernando

    2017-09-05

    Seizures increase prostaglandin and cytokine levels in the brain. However, it remains to be determined whether cyclooxygenase-2 (COX-2) derived metabolites play a role in seizure-induced cytokine increase in the brain and whether anticonvulsant activity is shared by all COX-2 inhibitors. In this study we investigated whether three different COX-2 inhibitors alter pentylenetetrazol (PTZ)-induced seizures and increase of interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex of mice. Adult male albino Swiss mice received nimesulide, celecoxib or etoricoxib (0.2, 2 or 20mg/kg in 0.1% carboxymethylcellulose (CMC) in 5% Tween 80, p.o.). Sixty minutes thereafter the animals were injected with PTZ (50mg/kg, i.p.) and the latency to myoclonic jerks and to generalized tonic-clonic seizures were recorded. Twenty minutes after PTZ injection animals were killed and cytokine levels were measured. PTZ increased cytokine levels in the cerebral cortex and hippocampus. While celecoxib and nimesulide attenuated PTZ -induced increase of proinflammatory cytokines in the cerebral cortex, etoricoxib did not. Nimesulide was the only COX-2 inhibitors that attenuated PTZ-induced seizures. This effect coincided with an increase of IL-10 levels in the cerebral cortex and hippocampus, constituting circumstantial evidence that IL-10 increase may be involved in the anticonvulsant effect of nimesulide. Copyright © 2017. Published by Elsevier B.V.

  2. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri.

    Science.gov (United States)

    Mathew, Jobin; Paul, Jes; Nandhu, M S; Paulose, C S

    2010-09-01

    We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.

  3. Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome.

    Science.gov (United States)

    Basu, Arpita; Betts, Nancy M; Mulugeta, Afework; Tong, Capella; Newman, Emily; Lyons, Timothy J

    2013-03-01

    Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (α-carotene, β-carotene, lycopene) and tocopherols (α-tocopherol, γ-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively; P glutathione (1783 to 2395 μg/g hemoglobin and 1905 to 2751 μg/g hemoglobin, respectively; P glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 μg/dL, P green tea may provide antioxidant protection in the metabolic syndrome.

  4. Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats

    OpenAIRE

    Rebolledo-Solleiro, Daniela; Roldán-Roldán, Gabriel; Díaz, Daniel; Velasco, Myrian; Larqué, Carlos; Rico-Rosillo, Guadalupe; Vega-Robledo, Gloria Bertha; Zambrano, Elena; Hiriart, Marcia; Pérez de la Mora, Miguel

    2017-01-01

    Metabolic syndrome (MS) is a cluster of signs that increases the risk to develop diabetes mellitus type 2 and cardiovascular disease. In the last years, a growing interest to study the relationship between MS and psychiatric disorders, such as depression and anxiety, has emerged obtaining conflicting results. Diet-induced MS rat models have only examined the effects of high-fat or mixed cafeteria diets to a limited extent. We explored whether an anxiety-like behavior was associated with MS in...

  5. Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients: A Longitudinal Study.

    Science.gov (United States)

    Chai, Chao; Wang, Zhiye; Fan, Linlin; Zhang, Mengjie; Chu, Zhiqiang; Zuo, Chao; Liu, Lei; Mark Haacke, E; Guo, Wenmei; Shen, Wen; Xia, Shuang

    2016-03-01

    The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs).Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores.CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P CMBs and MMSE, 9 patients had scores CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = -0.673, P = 0.023).The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP.

  6. Clopidogrel use is associated with an increased prevalence of cerebral microbleeds in a stroke-free population: the Rotterdam study.

    Science.gov (United States)

    Darweesh, Sirwan K L; Leening, Maarten J G; Akoudad, Saloua; Loth, Daan W; Hofman, Albert; Ikram, M Arfan; Vernooij, Meike W; Stricker, Bruno H

    2013-09-26

    Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke. We performed a cross-sectional analysis using data from the Rotterdam Study, a prospective population-based cohort of persons aged 45 years and older. Among 4408 stroke-free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever-users and 4287 never-users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (> 4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19. In stroke-free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibility of residual confounding in this study.

  7. Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients

    Science.gov (United States)

    Chai, Chao; Wang, Zhiye; Fan, Linlin; Zhang, Mengjie; Chu, Zhiqiang; Zuo, Chao; Liu, Lei; Mark Haacke, E.; Guo, Wenmei; Shen, Wen; Xia, Shuang

    2016-01-01

    Abstract The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs). Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores. CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P CMBs and MMSE, 9 patients had scores CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = −0.673, P = 0.023). The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP. PMID:27015171

  8. Clopidogrel Use Is Associated With an Increased Prevalence of Cerebral Microbleeds in a Stroke‐Free Population: The Rotterdam Study

    Science.gov (United States)

    Darweesh, Sirwan K.L.; Leening, Maarten J.G.; Akoudad, Saloua; Loth, Daan W.; Hofman, Albert; Arfan Ikram, M.; Vernooij, Meike W.; Stricker, Bruno H.

    2013-01-01

    Background Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke. Methods and Results We performed a cross‐sectional analysis using data from the Rotterdam Study, a prospective population‐based cohort of persons aged 45 years and older. Among 4408 stroke‐free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever‐users and 4287 never‐users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (>4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19. Conclusions In stroke‐free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibility of residual confounding in this study. PMID:24072532

  9. Metabolic encephalopathies.

    Science.gov (United States)

    Angel, Michael J; Young, G Bryan

    2011-11-01

    Kinnier Wilson coined the term metabolic encephalopathy to describe a clinical state of global cerebral dysfunction induced by systemic stress that can vary in clinical presentation from mild executive dysfunction to deep coma with decerebrate posturing; the causes are numerous. Some mechanisms by which cerebral dysfunction occurs in metabolic encephalopathies include focal or global cerebral edema, alterations in transmitter function, the accumulation of uncleared toxic metabolites, postcapillary venule vasogenic edema, and energy failure. This article focuses on common causes of metabolic encephalopathy, and reviews common causes, clinical presentations and, where relevant, management.

  10. Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng; Luo, Huai-Rong

    2017-01-01

    Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan.

  11. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-05-28

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.

  12. Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Joan

    2011-01-01

    Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow. Activity-dependent rises in CMRO2 fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca2+ stimulate oxidative metabolism vi...

  13. NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism.

    Science.gov (United States)

    Chrysovergis, K; Wang, X; Kosak, J; Lee, S-H; Kim, J S; Foley, J F; Travlos, G; Singh, S; Baek, S J; Eling, T E

    2014-12-01

    Obesity is a major health problem associated with high morbidity and mortality. NSAID-activated gene (NAG-1) is a TGF-β superfamily member reported to alter adipose tissue levels in mice. We investigated whether hNAG-1 acts as a regulator of adiposity and energy metabolism. hNAG-1 mice, ubiquitously expressing hNAG-1, were placed on a control or high-fat diet for 12 weeks. hNAG-1-expressing B16/F10 melanoma cells were used in a xenograft model to deliver hNAG-1 to obese C57BL/6 mice. As compared with wild-type littermates, transgenic hNAG-1 mice have less white fat and brown fat despite equivalent food intake, improved glucose tolerance, lower insulin levels and are resistant to dietary- and genetic-induced obesity. hNAG-1 mice are more metabolically active with higher energy expenditure. Obese C57BL/6 mice treated with hNAG-1-expressing xenografts show decreases in adipose tissue and serum insulin levels. hNAG-1 mice and obese mice treated with hNAG-1-expressing xenografts show increased thermogenic gene expression (UCP1, PGC1α, ECH1, Cox8b, Dio2, Cyc1, PGC1β, PPARα, Elvol3) in brown adipose tissue (BAT) and increased expression of lipolytic genes (Adrb3, ATGL, HSL) in both white adipose tissue (WAT) and BAT, consistent with higher energy metabolism. hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance.

  14. A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

    Science.gov (United States)

    Simon, Aaron B; Griffeth, Valerie E M; Wong, Eric C; Buxton, Richard B

    2013-01-01

    Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL) and Blood Oxygenation Level Dependent (BOLD) imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP) estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged.

  15. A novel method of combining blood oxygenation and blood flow sensitive magnetic resonance imaging techniques to measure the cerebral blood flow and oxygen metabolism responses to an unknown neural stimulus.

    Directory of Open Access Journals (Sweden)

    Aaron B Simon

    Full Text Available Simultaneous implementation of magnetic resonance imaging methods for Arterial Spin Labeling (ASL and Blood Oxygenation Level Dependent (BOLD imaging makes it possible to quantitatively measure the changes in cerebral blood flow (CBF and cerebral oxygen metabolism (CMRO(2 that occur in response to neural stimuli. To date, however, the range of neural stimuli amenable to quantitative analysis is limited to those that may be presented in a simple block or event related design such that measurements may be repeated and averaged to improve precision. Here we examined the feasibility of using the relationship between cerebral blood flow and the BOLD signal to improve dynamic estimates of blood flow fluctuations as well as to estimate metabolic-hemodynamic coupling under conditions where a stimulus pattern is unknown. We found that by combining the information contained in simultaneously acquired BOLD and ASL signals through a method we term BOLD Constrained Perfusion (BCP estimation, we could significantly improve the precision of our estimates of the hemodynamic response to a visual stimulus and, under the conditions of a calibrated BOLD experiment, accurately determine the ratio of the oxygen metabolic response to the hemodynamic response. Importantly we were able to accomplish this without utilizing a priori knowledge of the temporal nature of the neural stimulus, suggesting that BOLD Constrained Perfusion estimation may make it feasible to quantitatively study the cerebral metabolic and hemodynamic responses to more natural stimuli that cannot be easily repeated or averaged.

  16. 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)

  17. Relation of EEG alpha background to cognitive fuction, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes

    Energy Technology Data Exchange (ETDEWEB)

    Devinsky, O.; Sato, S.; Conwit, R.A.; Schapiro, M.B. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1990-01-01

    We studied 19 young adults (19 to 37 years old) and 9 older patients (42 to 66 years old) with Down's syndrome (DS) and a control group of 13 healthy adults (22 to 38 years old) to investigate the relation of electroencephalographic (EEG) alpha background to cognitive function and cerebral metabolism. Four of the older patients with DS had a history of mental deterioration, disorientation, and memory loss and were demented. Patients and control subjects had EEGs, psychometric testing, quantitative computed tomography, and positron emission tomography with fludeoxyglucose F 18. A blinded reader classified the EEGs into two groups--those with normal alpha background or those with abnormal background. All the control subjects, the 13 young adult patients with DS, and the 5 older patients with DS had normal EEG backgrounds. In comparison with the age-matched patients with DS with normal alpha background, older patients with DS with decreased alpha background had dementia, fewer visuospatial skills, decreased attention span, larger third ventricles, and a global decrease in cerebral glucose utilization with parietal hypometabolism. In the young patients with DS, the EEG background did not correlate with psychometric or positron emission tomographic findings, but the third ventricles were significantly larger in those with abnormal EEG background. The young patients with DS, with or without normal EEG background, had positron emission tomographic findings similar to those of the control subjects. The mechanism underlying the abnormal EEG background may be the neuropathologic changes of Alzheimer's disease in older patients with DS and may be cerebral immaturity in younger patients with DS.

  18. Changes in metabolism of cerebral glucose after stereotactic leukotomy for refractory obsessive-compulsive disorder: a case report.

    Science.gov (United States)

    Biver, F; Goldman, S; François, A; De La Porte, C; Luxen, A; Gribomont, B; Lotstra, F

    1995-01-01

    Brain glucose metabolism was investigated with PET and [18F]fluorodeoxyglucose, before and after a bifrontal stereotactic leukotomy in a 37 year old woman with refractory obsessive-compulsive disorder. A bilateral decrease in glucose metabolism was found in the orbital frontal cortex after psychosurgery. Glucose metabolism was decreased to a lesser degree in Brodmann's area 25, in the thalamus, and in the caudate nucleus. Clinical improvement in obsessive-compulsive disorder after stereotactic tractotomy seems to be associated with metabolic changes in the brain, in particular, in the orbital part of the frontal lobe. Images PMID:7738568

  19. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise

    DEFF Research Database (Denmark)

    Avnstorp, Magnus B; Rasmussen, Peter; Brassard, Patrice

    2015-01-01

    Avnstorp, Magnus B., Peter Rasmussen, Patrice Brassard, Thomas Seifert, Morten Overgaard, Peter Krustrup, Niels H. Secher, and Nikolai B. Nordsborg. Cerebral water and ion balance remains stable when humans are exposed to acute hypoxic exercise. High Alt Med Biol 16:000-000, 2015.-Background...... metabolism and increased an index of cerebral blood flow, but cerebral net water and ion homeostasis remained stable. Thus, although AMS develops within hours and may be related to exercise-induced disturbance of cerebral ion and water balance, such changes are not detectable when subjects are exposed...

  20. 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...... that there is a general reduction in rCMRglc in long-term recurrence free survivors of childhood primary brain tumors treated with CRT in high doses (44-56 Gy)......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...

  1. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

  2. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  3. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  4. Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Seifert, Thomas; Secher, Niels H

    2015-01-01

    CONTEXT: 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. OBJECTIVES: The object......CONTEXT: 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. OBJECTIVES......: The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism. DESIGN: Single trial. SETTING: Hospital. PARTICIPANT: Healthy post-absorptive males (n = 6). INTERVENTIONS: Subjects were studied under basal condition and three...... 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...

  5. Metabolic flux phenotype of tobacco hairy roots engineered for increased geraniol production.

    Science.gov (United States)

    Masakapalli, Shyam K; Ritala, Anneli; Dong, Lemeng; van der Krol, Alexander R; Oksman-Caldentey, Kirsi-Marja; Ratcliffe, R George; Sweetlove, Lee J

    2014-03-01

    The goal of this study was to characterise the metabolic flux phenotype of transgenic tobacco (Nicotiana tabacum) hairy roots engineered for increased biosynthesis of geraniol, an intermediate of the terpenoid indole alkaloid pathway. Steady state, stable isotope labelling was used to determine flux maps of central carbon metabolism for transgenic lines over-expressing (i) plastid-targeted geraniol synthase (pGES) from Valeriana officinalis, and (ii) pGES in combination with plastid-targeted geranyl pyrophosphate synthase from Arabidopsis thaliana (pGES+pGPPS), as well as for wild type and control-vector-transformed roots. Fluxes were constrained by the redistribution of label from [1-¹³C]-, [2-¹³C]- or [¹³C6]glucose into amino acids, sugars and organic acids at isotopic steady state, and by biomass output fluxes determined from the fractionation of [U-¹⁴C]glucose into insoluble polymers. No significant differences in growth and biomass composition were observed between the lines. The pGES line accumulated significant amounts of geraniol/geraniol glycosides (151±24 ng/mg dry weight) and the de novo synthesis of geraniol in pGES was confirmed by ¹³C labelling analysis. The pGES+pGPPS also accumulated geraniol and geraniol glycosides, but to lower levels than the pGES line. Although there was a distinct impact of the transgenes at the level of geraniol synthesis, other network fluxes were unaffected, reflecting the capacity of central metabolism to meet the relatively modest demand for increased precursors in the transgenic lines. It is concluded that re-engineering of the terpenoid indole alkaloid pathway will only require simultaneous manipulation of the steps producing the pathway precursors that originate in central metabolism in tissues engineered to produce at least an order of magnitude more geraniol than has been achieved so far.

  6. Metabolic engineering of Caldicellulosiruptor bescii yields increased hydrogen production from lignocellulosic biomass

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Minseok [University of Georgia, Athens, GA; Chung, Daehwan [University of Georgia, Athens, GA; Elkins, James G [ORNL; Guss, Adam M [ORNL; Westpheling, Janet [University of Georgia, Athens, GA

    2013-01-01

    Background: Members of the anaerobic thermophilic bacterial genus Caldicellulosiruptor are emerging candidates for consolidated bioprocessing (CBP) because they are capable of efficiently growing on biomass without conventional pretreatment. C. bescii produces primarily lactate, acetate and hydrogen as fermentation products, and while some Caldicellulosiruptor strains produce small amounts of ethanol C. bescii does not, making it an attractive background to examine the effects of metabolic engineering. The recent development of methods for genetic manipulation has set the stage for rational engineering of this genus for improved biofuel production. Here, we report the first targeted gene deletion, the gene encoding lactate dehydrogenase (ldh), for metabolic engineering of a member of this genus. Results: A deletion of the C. bescii L-lactate dehydrogenase gene (ldh) was constructed on a non-replicating plasmid and introduced into the C. bescii chromosome by marker replacement. The resulting strain failed to produce detectable levels of lactate from cellobiose and maltose, instead increasing production of acetate and H2 by 21-34% relative to the wild type and pyrFA parent strains. The same phenotype was observed on a real-world substrate switchgrass (Panicum virgatum). Furthermore, the ldh deletion strain grew to a higher maximum optical density than the wild type on maltose and cellobiose, consistent with the prediction that the mutant would gain additional ATP with increased acetate production. Conclusions: Deletion of ldh in C. bescii is the first use of recently developed genetic methods for metabolic engineering of these bacteria. This deletion resulted in a redirection of electron flow from production of lactate to acetate and hydrogen. New capabilities in metabolic engineering combined with intrinsic utilization of lignocellulosic materials position these organisms to provide a new paradigm for consolidated bioprocessing of fuels and other products from

  7. Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder.

    Science.gov (United States)

    Ramage, Amy E; Litz, Brett T; Resick, Patricia A; Woolsey, Mary D; Dondanville, Katherine A; Young-McCaughan, Stacey; Borah, Adam M; Borah, Elisa V; Peterson, Alan L; Fox, Peter T

    2016-02-01

    Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.

  8. Clinical Neuroimaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji [Nakamura Memorial Hospital, Sapporo (Japan)

    1999-06-01

    Notice points in clinical imaging of cerebral ischemia are reviewed. When cerebral blood flow is determined in acute stage of cerebral embolism (cerebral blood flow SPECT), it is important to find area of ischemic core and ischemic penumbra. When large cortex area is assigned to ischemic penumbra, thrombolytic therapy is positively adapted, but cautious correspondence is necessary when ischemic core is recognized. DWI is superior in the detection of area equivalent to ischemic core of early stage, but, in imaging of area equivalent to ischemic penumbra, perfusion image or distribution image of cerebral blood volume (CBV) by MRI need to be combined. Luxury perfusion detected by cerebral blood flow SPECT in the cases of acute cerebral embolism suggests vascular recanalization, but a comparison with CT/MRI and continuous assessment of cerebral circulation dynamics were necessary in order to predict brain tissue disease (metabolic abnormality). In hemodynamic cerebral ischemia, it is important to find stage 2 equivalent to misery perfusion by quantification of cerebral blood flow SPECT. Degree of diaschisis can indicate seriousness of brain dysfunction for lacuna infarct. Because cerebral circulation reserve ability (perfusion pressure) is normal in all areas of the low cerebral blood flow by diaschisis mechanism, their areas are easily distinguished from those of hemodynamic cerebral ischemia. (K.H.)

  9. Erythropoietin Pretreatment of Transplanted Endothelial Colony-Forming Cells Enhances Recovery in a Cerebral Ischemia Model by Increasing Their Homing Ability: A SPECT/CT Study.

    Science.gov (United States)

    Garrigue, Philippe; Hache, Guillaume; Bennis, Youssef; Brige, Pauline; Stalin, Jimmy; Pellegrini, Lionel; Velly, Lionel; Orlandi, Francesca; Castaldi, Elena; Dignat-George, Françoise; Sabatier, Florence; Guillet, Benjamin

    2016-11-01

    Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients with an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hindlimb ischemia. The present study used SPECT/CT to evaluate whether priming of ECFCs with erythropoietin could enhance their homing to the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effect on blood-brain barrier (BBB) disruption, cerebral apoptosis, and cerebral blood flow (CBF). Rats underwent a 1-h MCAO followed by reperfusion and then 1 d after MCAO received an intravenous injection of either PBS (control, n = 10), PBS-primed ECFCs (ECFCPBS, n = 13), or erythropoietin-primed ECFCs (ECFCEPO, n = 10). ECFC homing and the effect on BBB disruption, cerebral apoptosis, and CBF were evaluated by SPECT/CT up to 14 d after MCAO. The results were expressed as median ± interquartile range for ipsilateral-to-contralateral ratio of the activity in middle cerebral artery-vascularized territories in each hemisphere. Histologic evaluation of neuronal survival and astrocytic proliferation was performed on day 14. Erythropoietin priming increased homing of ECFCs to the ischemic hemisphere (ECFCPBS, 111.0% ± 16.0%; ECFCEPO, 146.5% ± 13.3%). BBB disruption was significantly reduced (control, 387% ± 153%; ECFCPBS, 151% ± 46% [P < 0.05]; ECFCEPO, 112% ± 9% [P < 0.001]) and correlated negatively with ECFC homing (Pearson r = -0.6930, P = 0.0002). Cerebral apoptosis was significantly reduced (control, 161% ± 10%; ECFCPBS, 141% ± 9% [P < 0.05]; ECFCEPO,118% ± 5% [P < 0.001]) and correlated negatively with ECFC homing (r = -0.7251, P < 0.0001). CBF was significantly restored with ECFCs and almost totally so with erythropoietin priming (control, 72% ± 2

  10. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  11. Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

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    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

  12. Increased expression of fatty-acid and calcium metabolism genes in failing human heart.

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    Vanessa García-Rúa

    Full Text Available BACKGROUND: Heart failure (HF involves alterations in metabolism, but little is known about cardiomyopathy-(CM-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA uptake and oxidation or in calcium-(Ca(2+-handling in the human heart. METHODS: RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36 without diabetes mellitus of ischaemic (ICM, n = 16 or dilated (DCM, n = 20 cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6. RESULTS: Significant increases in mRNA of genes regulating FA uptake (CD36 and intracellular transport (Heart-FA-Binding Protein (HFABP were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA, PPAR-gamma coactivator-1-alpha (PGC1A and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+-handling genes (Two-Pore-Channel 1 (TPCN1, Two-Pore-Channel 2 (TPCN2, and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1 increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL: three were common to and three distinct from ICM. CONCLUSION: DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2

  13. Amelioration of age-dependent increase in protein carbonyls of cerebral hemispheres of mice by melatonin and ascorbic acid.

    Science.gov (United States)

    Dkhar, Preeticia; Sharma, Ramesh

    2011-12-01

    Melatonin secreted by the pineal gland acts as a free radical scavenger besides its role as a hormonal signaling agent. It detoxifies a variety of free radicals and reactive oxygen intermediates including hydroxyl radical, peroxynitrite anion and singlet oxygen. Ascorbic acid (Vitamin C), a water soluble vitamin, is a naturally occurring antioxidant and cofactor in various enzymes. Protein carbonyls are formed as a consequence of the oxidative modification of proteins by reactive oxygen species. Oxidative modification alters the function of protein and is thought to play an important role in the decline of cellular functions during aging. In the present study, the effect of melatonin and ascorbic acid on age-related carbonyl content of cerebral hemispheres in mice was investigated. Protein carbonyls of cerebral hemispheres have been found to be significantly higher in 18-month-old mice as compared to 1-month old mice. Administration of a single dose of melatonin (10 mg/kg body weight) and ascorbic acid (10 mg/kg body weight) intraperitoneally for three consecutive days decreases the carbonyl content in 1- and 18-month-old mice significantly. The present study thus suggests that the formation of protein carbonyls in the cerebral hemispheres of the aging mice can be prevented by the antioxidative effects of melatonin and ascorbic acid that could in turn be beneficial in having health benefits from age-related neurodegenerative diseases.

  14. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco;

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid...... preceded by an early RA-induced phosphorylation of p38 mitogen-activated protein kinase. UCP1 expression was not induced. CONCLUSION: The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism....

  15. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    OpenAIRE

    Vaughan Roger A; Garcia-Smith Randi; Bisoffi Marco; Conn Carole A; Trujillo Kristina A

    2012-01-01

    Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA) or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determine...

  16. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.

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    Niraj K Nirala

    2013-06-01

    Full Text Available The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in

  17. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  18. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  19. Early evaluation of cerebral metabolic rate of glucose (CMRglu) with {sup 18}F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Maria Lucia; Lavalle, Mariadea; Leccisotti, Lucia; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Institute of Nuclear Medicine, Rome (Italy); Mangiola, Annunziato; De Bonis, Pasquale; Anile, Carmelo [Universita Cattolica del Sacro Cuore, Institute of Neurosurgery, Rome (Italy); Indovina, Luca [Universita Cattolica del Sacro Cuore, Institute of Physics, Rome (Italy); Marra, Camillo [Universita Cattolica del Sacro Cuore, Institute of Neurology, Rome (Italy); Pelliccioni, Armando [Istituto Nazionale per l' Assicurazione contro gli Infortuni sul Lavoro (INAIL), Rome (Italy)

    2012-02-15

    We evaluated the relationships between the cerebral metabolic rate of glucose (CMRglu) measured by dynamic {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the clinical and neuropsychological assessment before and after the surgical procedure in idiopathic normal pressure hydrocephalus (INPH) patients. Eleven selected INPH patients underwent clinical assessment (modified Rankin scale, Krauss scale, Larsson categorization system and Stein-Langfitt scale), cognitive evaluation (Mini-Mental State Examination, MMSE) and dynamic {sup 18}F-FDG PET/CT scan 3 days before and 1 week after ventricular shunt placement. After shunting, the global CMRglu significantly increased (2.95 {+-} 0.44 vs 4.38 {+-} 0.68, p = 10{sup -7}) in all INPH patients with a mean percentage value of 48.7%. After shunting, no significant change was found in the Evans ratio whereas a significant decrease in all clinical scale scores was observed. Only a slight reduction in the MMSE was found. After shunting, a significant correlation between the global CMRglu value and clinical assessment was found (R {sup 2} = 0.75, p = 0.024); indeed all clinical scale scores varied (decreasing) and the CMRglu value also varied (increasing) in all INPH patients. Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of ''neuronal plasticity'' and for the cells' reactivity in order to recover their metabolic function. (orig.)

  20. Continued improvement of cardiovascular mortality in Hungary - impact of increased cardio-metabolic prescriptions

    Directory of Open Access Journals (Sweden)

    Jozan Peter

    2010-07-01

    Full Text Available Abstract Background During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior. Methods Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered. Results We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI. The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome. Conclusions These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.

  1. Metabolic alterations in the human erythrocyte produced by increases in glucose concentration

    Science.gov (United States)

    Travis, Susan F.; Morrison, Anthony D.; Clements, Rex S.; Winegrad, Albert I.; Oski, Frank A.

    1971-01-01

    Human erythrocytes incubated in medium containing 50 mM glucose have increased intracellular sorbitol and fructose concentrations as compared with samples incubated with 5 mM glucose. Increased medium glucose concentration did not significantly alter total glucose consumption or lactate production. However, the intracellular lactate:pyruvate ratio rose, the concentrations of fructose diphosphate, and triose phosphates increased, and the 2,3-diphosphoglycerate concentration fell. [14C]O2 production from glucose-1-14C also increased with increased medium glucose concentration. These changes are believed to reflect changes in the redox states of the diphosphopyridine nucleotide/reduced form of diphosphopyridine nucleotide (NAD/NADH) and nicotinamide—adenine dinucleotide phosphate/reduced form of nicotinamide—adenine dinucleotide phosphate (NADP/NADPH) couples resulting from increased activity of the polyol pathway. Addition of pyruvate to the incubation media prevented these changes. These studies illustrate that an increase in the red cell's normal substrate, glucose, can produce changes in red cell metabolism. PMID:4398937

  2. 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.

  3. All-trans retinoic acid increases oxidative metabolism in mature adipocytes

    DEFF Research Database (Denmark)

    Mercader, Josep; Madsen, Lise; Felipe, Francisco;

    2007-01-01

    BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid...... metabolism and related gene expression were analyzed in differentiated 3T3-L1 adipocytes after exposure to RA or vehicle. RESULTS: Treatment with RA resulted in decreased cellular triacylglycerol content and increased basal lipolysis and fatty acid oxidation rate. At the mRNA level, RA treatment led......), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were...

  4. Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients

    OpenAIRE

    Chai, Chao; Wang, Zhiye; Fan, Linlin; Zhang, Mengjie; Chu, Zhiqiang; Zuo, Chao; Liu, Lei; E. Mark Haacke; Guo, Wenmei; Shen, Wen; Xia, Shuang

    2016-01-01

    Abstract The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs). Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups wit...

  5. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  6. Energy dense, protein restricted diet increases adiposity and perturbs metabolism in young, genetically lean pigs.

    Directory of Open Access Journals (Sweden)

    Kimberly D Fisher

    Full Text Available Animal models of obesity and metabolic dysregulation during growth (or childhood are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12, containing 15% tallow, 35% refined sugars and 9.1-12.9% crude protein, or a control corn-based diet (n = 11 with 12.2-19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001 energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT; blood glucose increased (P<0.05 in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01, even 4 h post-challenge. During OGTT, glucose area under the curve (AUC was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001. Chronic HED intake increased (P<0.05 subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7 was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.

  7. Increased serum hepcidin levels in subjects with the metabolic syndrome: a population study.

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