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Sample records for cerebral metabolic features

  1. STUDIES IN CEREBRAL METABOLISM

    PubMed Central

    Gordan, Gilbert S.; Adams, John E.; Bentinck, Richard C.; Eisenberg, Eugene; Harper, Harold; Hobson, Quentin J. G.

    1953-01-01

    In numerous clinical observations, it has been noted that steroid hormones have effects upon the central nervous system. Earlier interpretations of this relationship were largely speculative until newer methods permitted quantitation of actions of hormones and hormonal deficiencies on cerebral metabolism. The present studies indicate that certain steroids which affect behavior also influence cerebral metabolism. PMID:13019600

  2. [Cerebral hydatid disease: imaging features].

    PubMed

    Tlili-Graiess, K; El-Ouni, F; Gharbi-Jemni, H; Arifa, N; Moulahi, H; Mrad-Dali, K; Guesmi, H; Abroug, S; Yacoub, M; Krifa, H

    2006-12-01

    Cerebral hytatid cysts (HC) are extremely rare, forming 2% of all intra cranial space occupying lesions even in counties where the disease is endemic. HC diagnosis is usually based on a pathognomonic computed tomography (CT) pattern. In order to assess the value of MR we reviewed the CT (n=25) and magnetic resonance (MR, n=4 including diffusion and proton magnetic resonance spectroscopy in 1) imaging of 25 patients with pathologically confirmed cerebral hydatid disease. 19 HC were seen in children under 16 years. All were supra tentorial with 22 in the middle cerebral artery territory. HC was solitary in 18 cases, unilocular in 23 and multi-vesicular in 2 with heavily calcified pericyst in 1. 2 cysts were intra ventricular and 1 intra aqueducal. The most typical features were well defined, smooth thin walled spherical or oval cystic lesions of CSF density and/or signal with considerable mass effect (20/25). Surrounding oedema with complete or incomplete rim enhancement was seen in 3 cases which were labelled as complicated and/or infected cysts. Although CT is diagnostic of hydatid disease in almost all cases (22/25), MRI including diffusion and spectroscopy precisely demonstrate location, number, cyst capsule, type of signal and enhancement and allows diagnosis of atypical or complicated HC and appears more helpful in surgical planning.

  3. Features to validate cerebral toxoplasmosis.

    PubMed

    Correia, Carolina da Cunha; Melo, Heloísa Ramos Lacerda; Costa, Vláudia Maria Assis; Brainer, Alessandra Mertens

    2013-01-01

    Neurotoxoplasmosis (NT) sometimes manifests unusual characteristics. We analyzed 85 patients with NT and AIDS according to clinical, cerebrospinal fluid, cranial magnetic resonance, and polymerase chain reaction (PCR) characteristics. In 8.5%, focal neurological deficits were absent and 16.4% had single cerebral lesions. Increased sensitivity of PCR for Toxoplasma gondii DNA in the central nervous system was associated with pleocytosis and presence of >4 encephalic lesions. Patients with NT may present without focal neurological deficit and NT may occur with presence of a single cerebral lesion. Greater numbers of lesions and greater cellularity in cerebrospinal fluid improve the sensitivity of PCR to T gondii.

  4. Hyperglycemia accelerates apparent diffusion coefficient-defined lesion growth after focal cerebral ischemia in rats with and without features of metabolic syndrome.

    PubMed

    Tarr, David; Graham, Delyth; Roy, Lisa A; Holmes, William M; McCabe, Christopher; Mhairi Macrae, I; Muir, Keith W; Dewar, Deborah

    2013-10-01

    Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

  5. Cerebral metabolic adaptation and ketone metabolism after brain injury.

    PubMed

    Prins, Mayumi L

    2008-01-01

    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.

  6. Cerebral metabolic adaptation and ketone metabolism after brain injury

    PubMed Central

    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

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

    SciTech Connect

    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.

  8. Electroencephalographic and clinical features of cerebral malaria

    PubMed Central

    Crawley, J; Smith, S; Muthinji, P; Marsh, K; Kirkham, F

    2001-01-01

    BACKGROUND—Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study.
METHODS—Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly intervals until recovery of consciousness. Ten deeply comatose children underwent intracranial pressure monitoring. Children were not mechanically ventilated, which made it possible to directly correlate the clinical and EEG findings.
RESULTS—Of 65 children aged 9 months and above, 40 had one or more seizures, and 18 had an episode of status epilepticus. Most seizures were partial motor, and spike wave activity consistently arose from the posterior temporo-parietal region, a border zone area lying between territories supplied by the carotid and vertebrobasilar circulations. Fifteen children had seizures that were clinically subtle or electrographic. Clinical seizures were associated with an abrupt rise in intracranial pressure. Fifty children recovered fully, seven died, and eight had persistent neurological sequelae. Initial EEG recordings of very slow frequency, or with background asymmetry, burst suppression, or interictal discharges, were associated with an adverse outcome.
CONCLUSIONS—Serial EEG recording has uncovered a range of clinical, subtle, and electrographic seizures complicating childhood cerebral malaria, and has emphasised their importance in the pathogenesis of coma. Further work is required to determine the most appropriate regimen for the prophylaxis and treatment of seizures in cerebral malaria, in order to improve outcome.

 PMID:11207176

  9. Cerebral ketone metabolism during development and injury.

    PubMed

    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.

  10. Cerebral Ketone Metabolism During Development and Injury

    PubMed Central

    Prins, Mayumi L.

    2011-01-01

    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. PMID:22104087

  11. Cerebral hemodynamics and cerebral metabolism during cold and warm stress.

    PubMed

    Doering, T J; Brix, J; Schneider, B; Rimpler, M

    1996-01-01

    .001) was measured at the end of the stimulus in comparison with the preliminary phase. Crossover analysis showed no significant period effects and intraindividual changes between period and treatment. Therefore, both treatments can be compared within the individual using paired t test. Local cold and warm stimuli influence the cerebral hemodynamics and cerebral metabolism. Cerebral hemodynamics (CBFV(MCA) in comparison with cerebral metabolism (cCytaa3, cHbO2) show opposite reactions under thermo-stress. Of special interest is the overshooting counter-regulation of cerebral metabolism after cold stimulation. These effects may open new thermotherapeutic aspects in central nervous system diseases.

  12. Epilepsy, cerebral blood flow, and cerebral metabolic rate.

    PubMed

    Duncan, R

    1992-01-01

    Penfield's observations in the 1930s provided the first systematic evidence of changes in regional cerebral blood flow (rCBF) associated with focal seizures. Further studies in humans and animals confirmed increases in cerebral blood flow and metabolism during generalised seizures, but the interictal, ictal, and postictal changes in focal epilepsy have begun to be elucidated in the last decade with the advent of in vivo imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) and, in the case of animal studies, of autoradiography. Most studies have been of temporal lobe epilepsy. Interictally, the characteristic finding has been reduced blood flow and/or metabolism in the affected temporal lobe, or more extensively in the ipsilateral hemisphere. The few studies to date of ictal or postictal changes have been of rCBF using SPECT. They show hyperperfusion of the whole temporal lobe ictally, hyperperfusion of the hippocampus, combined with hypoperfusion of lateral structures in the immediate postictal period. Later in the postictal period, hypoperfusion alone is seen. Studies of focal seizures in animals have shown hyperperfusion and hypermetabolism at the site of the focus often with widespread depression of both parameters in the ipsilateral neocortex. Limited studies of coupling between blood flow and metabolism in humans have suggested that flow during seizures is adequate for metabolic demand, although some animal studies have suggested localised areas of uncoupling. The results of modern in vivo imaging of ictal and postictal changes in blood flow and metabolism have correlated well with Penfield's observations, and these changes are now being used to help localise epileptic foci, allowing wider use of the surgical treatment he pioneered.

  13. Patterns of human local cerebral glucose metabolism during epileptic seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

    1982-10-01

    Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

  14. Cerebral blood flow and metabolism during sleep.

    PubMed

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

    PubMed Central

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

    2012-01-01

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

  16. Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

    PubMed

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

    2012-07-01

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

  17. Right cerebral hemiatrophy: neurocognitive and electroclinical features.

    PubMed

    Demirtas-Tatlidede, Asli; Yalcin, A Destina; Uysal, Ender; Forta, Hulki

    2010-04-01

    The purpose of this study was to retrospectively evaluate the cognitive and electroclinical characteristics of right cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome [DDMS]). Cognitive assessments with a particular emphasis on visuospatial functions, electroclinical features, and neuroimaging characteristics were analyzed for five patients with a clinically and neuroradiologically confirmed diagnosis of right-sided DDMS. Intelligence tests revealed mental retardation in all but one. Neuropsychological assessments demonstrated consistent impairments in tasks that have a spatial component (spatial processing and orientation discrimination), whereas attention, executive functions and verbal memory domains were variably impaired. Electroclinically, the main seizure types were simple partial motor, complex partial, and secondarily generalized seizures. Interictal EEG delineated lower amplitudes and slow background activity in the affected hemisphere. Overall, the cognitive performance of patients with DDMS encompasses a broad spectrum of impairments affecting multiple domains. Our findings support the concept that dorsal visual pathways responsible for spatial processing may be lateralized to the right hemisphere. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  18. Cerebral energy metabolism and microdialysis in neurocritical care.

    PubMed

    Nordström, Carl-Henrik

    2010-04-01

    It is of obvious clinical importance to monitor cerebral metabolism--in particular, cerebral energy metabolism and indicators of cellular damage-online at the bedside. The technique of cerebral microdialysis provides the opportunity for continuous monitoring of metabolic changes in the tissue before they are reflected in peripheral blood chemistry or in systemic physiological parameters. The basic idea of microdialysis is to mimic the function of a blood capillary by positioning a thin dialysis tube in the tissue and to be used to analyze the chemical composition of the interstitial fluid. The biochemical variables used during routine monitoring were chosen to cover important aspects of cerebral energy metabolism (glucose, pyruvate and lactate), to indicate excessive interstitial levels of excitatory transmitter substance (glutamate) and to give indications of degradation of cellular membranes (glycerol). Furthermore, pharmokinetic studies can be conducted using microdialysis. This article discusses technical and physiological aspects of microdialysis, and its clinical applications in brain injury.

  19. Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia

    SciTech Connect

    Kuhl, D.E.; Metter, E.J.; Benson, D.F.; Ashford, J.W.; Riege, W.H.; Fujikawa, D.G.; Markham, C.H.; Maltese, A.

    1985-05-01

    In the dementia of probable Alzheimer's Disease (AD), there is a decrease in the metabolic ratio of parietal cortex/caudate-thalamus which relates measures in the most and in the least severely affected locations. Since some demented patients with Parkinson's Disease (PDD) are known to share pathological and neurochemical features with AD patients, the authors evaluated if the distribution of cerebral hypometabolism in PDD and AD were the same. Local cerebral metabolic rates were determined using the FDG method and positron tomography in subjects with AD (N=23), and PDD (N=7), multiple infarct dementia (MID)(N=6), and controls (N=10). In MID, the mean par/caudthal ratio was normal (0.79 +- 0.9, N=6). In AD and PDD patients, this ratio correlated negatively with both the severity (r=-0.624, rho=0.001) and duration (r=-0.657, rho=0.001) of dementia. The ratio was markedly decreased in subjects with mild to severe dementia (0.46 +- 0.09, N=21) and with dementia duration greater than two years (0.44 +- 0.08, N=18), but the ratio was also significantly decreased in patients with less advanced disease, i.e., when dementia was only questionable (0.64 +- 0.14, N=9) (t=2.27, rho<0.037) and when duration was two years or less (0.62 +- 0.13, N=12)(t=2.88, rho<0.009). This similarity of hypometabolism in AD and PDD is additional evidence that a common mechanism may operate in both disorders. The par/caud-thal metabolic ratio may be an index useful in the differential diagnosis of early dementia.

  20. Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism

    PubMed Central

    Yaseen, Mohammad A.; Srinivasan, Vivek J.; Gorczynska, Iwona; Fujimoto, James G.; Boas, David A.; Sakadžić, Sava

    2015-01-01

    Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system’s design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. PMID:26713212

  1. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs

    SciTech Connect

    Busija, D.W.; Leffler, C.W. )

    1987-10-01

    The authors examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-{mu}m radioactive microspheres. Regional CBF ranged from 44 to 66 ml{center dot}min{sup {minus}1}{center dot}100 g{sup {minus}1}, and cerebral metabolic rate was 1.94 {plus minus} 0.23 ml O{sub 2}{center dot}100 g{sup {minus}1}{center dot}min{sup {minus}1} during normothermia (39{degree}C). Reduction of rectal temperature to 34-35{degree}C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, they examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilation during the second episode. They conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced.

  2. Multiple sclerosis with clinical and radiological features of cerebral tumour

    PubMed Central

    Sagar, HJ; Warlow, CP; Sheldon, PWE; Esiri, MM

    1982-01-01

    Three cases of multiple sclerosis, all confirmed pathologically, are described in whom both the unusual clinical features and the CT scan appearances suggested cerebral tumours. The failure of mass effect reliably to differentiate plaques and tumours on a CT scan is stressed and the literature relating to CT scanning in multiple sclerosis is reviewed. Images PMID:7131013

  3. Cerebral tumors: specific features in children.

    PubMed

    Koob, M; Girard, N

    2014-10-01

    Brain tumors are the second leading cause of cancer in children. Primary tumors predominate and are of very varied histological types. Their prognosis and treatment depend on the histological type and grade. The diagnostic approach to these includes analysis of the site of the lesion and appearances on computed tomography and MR, and taking account of the age and clinical features of the child. CT is used to diagnose the tumor in an emergency situation. Conventional MR provides a morphological approach and allows a staging assessment to be carried out before surgery. Advanced MR techniques (diffusion-weighted and perfusion imaging, MR spectroscopy) provide further information for the differential diagnosis, presumptive diagnosis of type and grade and to guide biopsy towards the most malignant areas in the lesion.

  4. Impact of pump flow rate during selective cerebral perfusion on cerebral hemodynamics and metabolism.

    PubMed

    Haldenwang, Peter L; Strauch, Justus T; Amann, Igor; Klein, Tobias; Sterner-Kock, Anja; Christ, Hildegard; Wahlers, Thorsten

    2010-12-01

    Although hypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic surgery, little is known about the ideal pump-flow management during this procedure. This study explored cerebral hemodynamics and metabolism at two different flow rates. Fourteen pigs (33 to 38 kg) were cooled on cardiopulmonary bypass to 25°C. After 10 minutes of hypothermic circulatory arrest, the animals were randomly assigned to 60 minutes of SCP at two different pump flow rates: 8 mL·kg(-1)·min(-1) (n = 7) and 18 mL·kg(-1)·min(-1) (n = 7). Microspheres were injected at baseline, coolest temperature, and at 5, 15, 25, and 60 minutes of SCP to calculate cerebral blood flow, cerebral vascular resistance, metabolic rate, and intracranial pressure. Cerebral blood flow decreased during cooling to 41% of the baseline value (from 57 ± 10 to 23 ± 4 mL·min(-1)·100 g(-1)). It recovered during the initial 15 minutes of SCP, showing a significantly higher increase (p = 0.017) at high-flow versus low-flow perfusion (139 ± 41 versus 75 ± 22 mL·min(-1)·100 g(-1)). After 60 minutes of SCP the cerebral blood flow almost returned to baseline values in the low-flow group (43 ± 25 mL·min(-1)·100 g(-1)), but showed an unexpected decrease (30 ± 7 mL·min(-1)·100 g(-1)) in the high-flow group. The highest regional cerebral blood flow was seen in the cortex (66 ± 12 mL·min(-1)·100 g(-1)), followed by the cerebellum (63 ± 12 mL·min(-1)·100 g(-1)), the pons (51 ± 17 mL·min(-1)·100 g(-1)), and the hippocampus (36 ± 9 mL·min(-1)·100 g(-1)). Intracranial pressure increased from 11 ± 3 to 13 ± 5 mm Hg during cooling on cardiopulmonary bypass. During low-flow SCP, it stayed stable at baseline values, whereas high-flow perfusion resulted in significantly higher intracranial pressures (17 ± 3 mm Hg; p = 0.001). Changes in cerebral vascular resistance and metabolic rate showed no significant differences between the groups. High-flow SCP provides no

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

    PubMed Central

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

    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

  6. Metabolic myopathies: clinical features and diagnostic approach.

    PubMed

    Smith, Edward C; El-Gharbawy, Areeg; Koeberl, Dwight D

    2011-05-01

    The rheumatologist is frequently called on to evaluate patients with complaints of myalgia, muscle cramps, and fatigue. The evaluation of these patients presents a diagnostic challenge given the nonspecific and intermittent nature of their complaints, often leading to inappropriate diagnostic testing. When these symptoms are associated with physical exertion, a metabolic myopathy should be suspected Although inflammatory myopathies may present with similar features, such a pattern should prompt a thorough evaluation for an underlying metabolic myopathy. This review discusses the most common causes of metabolic myopathies and reviews the current diagnostic options available to the clinician.

  7. An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia

    PubMed Central

    Liu, Mengting; Tang, Liying; Liu, Xin; Fang, Jing; Zhan, Hao; Wu, Hongwei; Yang, Hongjun

    2016-01-01

    In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers. PMID:27274780

  8. Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction

    SciTech Connect

    Lenzi, G.L.; Frackowiak, R.S.; Jones, T.

    1982-09-01

    Fifteen patients with acute cerebral hemispheric infarcts have been studied with positron emission tomography and the /sup 15/O steady-state inhalation technique. Thirteen follow-up studies were also performed. The values of cerebral oxygen metabolism (CMRO/sub 2/), cerebral blood flow (CBF), and oxygen extraction ration (OER) have been calculated for the infarcted regions, their borders, the symmetrical regions in contralateral cerebral hemispheres, and the cerebellar hemispheres. This study demonstrates that in the completed stroke there are thresholds for regional CMRO/sub 2/ and regional CBF below which the general clinical outcome of the patients is usually poor. The ischaemic lesions invariably produce an uncoupling between the greatly decreased metabolic demand and the less affected blood supply, with very frequent instances of relative hyperperfusion. Remote effects of the hemispheric infarcts have been demonstrated, such as crossed cerebellar diaschisis and contralateral transhemispheric depression. The level of consciousness correlates with oxygen uptake and blood flow both in the posterior fossa and in the contralateral cerebral hemispheres. The follow-up studies of individual patients underline the high variability of metabolism-to-flow balance during the acute phase of the illness, and stress the need for more studies focused on repeated assessments of homogeneous patient populations.

  9. Metabolic profiling reveals key metabolic features of renal cell carcinoma.

    PubMed

    Catchpole, Gareth; Platzer, Alexander; Weikert, Cornelia; Kempkensteffen, Carsten; Johannsen, Manfred; Krause, Hans; Jung, Klaus; Miller, Kurt; Willmitzer, Lothar; Selbig, Joachim; Weikert, Steffen

    2011-01-01

    Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.

  10. Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease.

    PubMed

    Hashimoto, Tetsuya; Yokota, Chiaki; Koshino, Kazuhiro; Shimomura, Ryo; Hino, Tenyu; Moriguchi, Tetsuaki; Hori, Yuki; Uehara, Toshiyuki; Minematsu, Kazuo; Iida, Hidehiro; Toyoda, Kazunori

    2016-08-01

    Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease. We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and (15)O-labeled gases. The functional values in the cortex-subcortex, basal ganglia, and centrum semiovale were compared between the two groups. Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1-91.5 mL vs. median: 11.3; range: 4.2-73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups. Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.

  11. Local cerebral metabolism during partial seizures

    SciTech Connect

    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 venous thrombosis imagiologic features in a pregnant woman].

    PubMed

    Ferreira, Maria Madalena; Rios, Ana Cristina; Fragata, Isabel; Baptista, José Tiago; Manaças, Rui; Reis, João

    2011-01-01

    Cerebral venous thrombosis (CVT) is a relatively rare but serious condition potentially reversible upon accurate diagnosis and adequate therapy. The peri-partum state and pregnancy are predisposing factors and TVC accounts for about 6% of maternal deaths. Its clinical symptoms depend on the the thrombus site and extension, and also on the existing collateral vessels network. We present the case of a 33 year-old woman, 13 weeks pregnant, that complained of headaches and whose cranial magnetic resonance imaging revealed a subtotal oclusión of the superior sagittal sinus. We discuss the imaging features of dural venous thrombosis in the acute phase.

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

    PubMed Central

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

    2012-01-01

    Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research. PMID:22186671

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

    PubMed

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

    2012-07-01

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

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

    SciTech Connect

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

    1985-05-01

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

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

    SciTech Connect

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. PET measurements of cerebral metabolism corrected for CSF contributions

    SciTech Connect

    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.

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

    SciTech Connect

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

    1989-01-01

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

  20. Effect of anxiety on cortical cerebral blood flow and metabolism

    SciTech Connect

    Gur, R.C.; Gur, R.E.; Resnick, S.M.; Skolnick, B.E.; Alavi, A.; Reivich, M.

    1987-04-01

    The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using /sup 18/Flurodeoxyglucose (/sup 18/FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between anxiety and performance.

  1. CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

    PubMed Central

    Mathew, Roy J.

    1994-01-01

    Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

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

    PubMed

    Yamaguchi, H; Yamauchi, H; Hazama, S; Hamamoto, H; Inoue, N

    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<0.001), and a significant increase in oxyhemoglobin (Oxy-Hb) of 13.9% (p=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=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=0.0022). Examination of the relationships between individual parameters showed that the percentage changes in rCBF and Oxy-Hb were significantly correlated (r=0.758,p=0.011). The percentage changes in rCBF and %Oxy-Hb were also correlated significantly (r=0.740,p=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. © 1999 Society of Photo-Optical Instrumentation Engineers.

  3. Cortical Cerebral Blood Flow, Oxygen Extraction Fraction, and Metabolic Rate in Patients with Middle Cerebral Artery Stenosis or Acute Stroke.

    PubMed

    Liu, Z; Li, Y

    2016-04-01

    With the advances of magnetic resonance technology, the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen can be measured in MRI. Our aim was to measure the CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen use in patients with different severities of middle cerebral artery stenosis or acute stroke by using the arterial spin-labeling and susceptibility-weighted imaging techniques. Fifty-seven patients with MCA stenosis or acute stroke were recruited and classified into 4 groups: mild MCA stenosis (group 1), severe MCA stenosis (group 2), occluded MCA (group 3), and acute stroke (group 4). Arterial spin-labeling and SWI sequences were used to acquire CBF, oxygen extraction fraction, and cerebral metabolic rate of oxygen. The oxygen extraction fraction in hemispheres with mild MCA stenosis (group 1) was remarkably higher than that in the contralateral hemisphere. In addition, hemispheres with severe MCA stenosis (group 2) had significantly lower CBF and a significantly higher oxygen extraction fraction than the contralateral hemisphere. Hemispheres with occluded MCA (group 3) or acute stroke (group 4) had a significantly lower CBF and cerebral metabolic rate of oxygen and a significantly higher oxygen extraction fraction than the contralateral hemisphere. The oxygen extraction fraction gradually increased in groups 1-3. When this offset a decrease in CBF, the cerebral metabolic rate of oxygen remained at a normal level. An occluded MCA led to reduction in both the CBF and cerebral metabolic rate of oxygen. Moreover, the oxygen extraction fraction and cerebral metabolic rate of oxygen significantly increased and decreased, respectively, in the occluded MCA region during acute stroke. © 2016 by American Journal of Neuroradiology.

  4. Serotonin modulation of cerebral glucose metabolism: sex and age effects.

    PubMed

    Munro, Cynthia A; Workman, Clifford I; Kramer, Elisse; Hermann, Carol; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; Smith, Gwenn S

    2012-11-01

    The serotonin system is implicated in a variety of psychiatric disorders whose clinical presentation and response to treatment differ between males and females, as well as with aging. However, human neurobiological studies are limited. Sex differences in the cerebral metabolic response to an increase in serotonin concentrations were measured, as well as the effect of aging, in men compared to women. Thirty-three normal healthy individuals (14 men/19 women, age range 20-79 years) underwent two resting positron emission tomography studies with the radiotracer [18F]-2-deoxy-2-fluoro-D-glucose ([(18)F]-FDG) after placebo and selective serotonin reuptake inhibitor (SSRI, citalopram) infusions on two separate days. Results indicated that women demonstrated widespread areas of increased cortical glucose metabolism with fewer areas of decrease in metabolism in response to citalopram. Men, in contrast, demonstrated several regions of decreased cortical metabolism, but no regions of increased metabolism. Age was associated with greater increases in women and greater decreases in men in most brain regions. These results support prior studies indicating that serotonin function differs in men and women across the lifespan. Future studies aimed at characterizing the influences of age and sex on the serotonin system in patients with psychiatric disorders are needed to elucidate the relationship between sex and age differences in brain chemistry and associated differences in symptom presentation and treatment response. Copyright © 2012 Wiley Periodicals, Inc.

  5. SEROTONIN MODULATION OF CEREBRAL GLUCOSE METABOLISM: SEX AND AGE EFFECTS

    PubMed Central

    Munro, Cynthia A.; Workman, Clifford; Kramer, Elisse; Hermann, Carol; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; Smith, Gwenn S.

    2012-01-01

    The serotonin system is implicated in a variety of psychiatric disorders whose clinical presentation and response to treatment differ between males and females, as well as with aging. However, human neurobiological studies are limited. Sex differences in the cerebral metabolic response to an increase in serotonin concentrations were measured, as well as the effect of aging, in men compared to women. Thirty-three normal healthy individuals (14 men/19 women, age range 20–79 years) underwent two resting positron emission tomography (PET) studies with the radiotracer [18F]-2-deoxy-2-fluoro-D-glucose ([18F]-FDG) after placebo and selective serotonin reuptake inhibitor (SSRI, citalopram) infusions on two separate days. Results indicated that women demonstrated widespread areas of increased cortical glucose metabolism with fewer areas of decrease in metabolism in response to citalopram. Men, in contrast, demonstrated several regions of decreased cortical metabolism, but no regions of increased metabolism. Age was associated with greater increases in women and greater decreases in men in most brain regions. These results support prior studies indicating that serotonin function differs in men and women across the lifespan. Future studies aimed at characterizing the influences of age and sex on the serotonin system in patients with psychiatric disorders are needed to elucidate the relationship between sex and age differences in brain chemistry and associated differences in symptom presentation and treatment response. PMID:22836227

  6. Cerebral metabolism of glucose in benign hereditary chorea

    SciTech Connect

    Suchowersky, O.; Hayden, M.R.; Martin, W.R.; Stoessl, A.J.; Hildebrand, A.M.; Pate, B.D.

    1986-01-01

    Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using YF-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC.

  7. Cerebral microvascular dysfunction in metabolic syndrome is exacerbated by ischemia-reperfusion injury.

    PubMed

    Obadia, Nathalie; Lessa, Marcos Adriano; Daliry, Anissa; Silvares, Raquel Rangel; Gomes, Fabiana; Tibiriçá, Eduardo; Estato, Vanessa

    2017-09-08

    Metabolic syndrome (MetS) is associated with an increased risk of cerebrovascular diseases, including cerebral ischemia. Microvascular dysfunction is an important feature underlying the pathophysiology of cerebrovascular diseases. In this study, we aimed to investigate the impacts of ischemia and reperfusion (IR) injury on the cerebral microvascular function of rats with high-fat diet-induced MetS. We examined Wistar rats fed a high-fat diet (HFD) or normal diet (CTL) for 20 weeks underwent 30 min of bilateral carotid artery occlusion followed by 1 h of reperfusion (IR) or sham surgery. Microvascular blood flow was evaluated on the parietal cortex surface through a cranial window by laser speckle contrast imaging, functional capillary density, endothelial function and endothelial-leukocyte interactions by intravital videomicroscopy. Lipid peroxidation was assessed by TBARs analysis, the expression of oxidative enzymes and inflammatory markers in the brain tissue was analyzed by real-time PCR. The cerebral IR in MetS animals induced a functional capillary rarefaction (HFD IR 117 ± 17 vs. CTL IR 224 ± 35 capillary/mm(2); p < 0.05), blunted the endothelial response to acetylcholine (HFD IR -16.93% vs. CTL IR 16.19% from baseline inner diameter p < 0.05) and increased the endothelial-leukocyte interactions in the venules in the brain. The impact of ischemia on the cerebral microvascular blood flow was worsened in MetS animals, with a marked reduction of cerebral blood flow, exposing brain tissue to a higher state of hypoxia. Our results demonstrate that during ischemia and reperfusion, animals with MetS are more susceptible to alterations in the cerebral microcirculation involving endothelial dysfunction and oxidative stress events.

  8. Sustained high-altitude hypoxia increases cerebral oxygen metabolism

    PubMed Central

    Smith, Zachary M.; Krizay, Erin; Guo, Jia; Shin, David D.; Scadeng, Miriam

    2013-01-01

    Acute mountain sickness (AMS) is a common condition occurring within hours of rapid exposure to high altitude. Despite its frequent occurrence, the pathophysiological mechanisms that underlie the condition remain poorly understood. We investigated the role of cerebral oxygen metabolism (CMRO2) in AMS. The purpose of this study was to test 1) if CMRO2 changes in response to hypoxia, and 2) if there is a difference in how individuals adapt to oxygen metabolic changes that may determine who develops AMS and who does not. Twenty-six normal human subjects were recruited into two groups based on Lake Louise AMS score (LLS): those with no AMS (LLS ≤ 2), and those with unambiguous AMS (LLS ≥ 5). [Subjects with intermediate scores (LLS 3–4) were not included.] CMRO2 was calculated from cerebral blood flow and arterial-venous difference in O2 content. Cerebral blood flow was measured using arterial spin labeling MRI; venous O2 saturation was calculated from the MRI of transverse relaxation in the superior sagittal sinus. Arterial O2 saturation was measured via pulse oximeter. Measurements were made during normoxia and after 2-day high-altitude exposure at 3,800 m. In all subjects, CMRO2 increased with sustained high-altitude hypoxia [1.54 (0.37) to 1.82 (0.49) μmol·g−1·min−1, n = 26, P = 0.045]. There was no significant difference in CMRO2 between AMS and no-AMS groups. End-tidal Pco2 was significantly reduced during hypoxia. Low arterial Pco2 is known to increase neural excitability, and we hypothesize that the low arterial Pco2 resulting from ventilatory acclimatization causes the observed increase in CMRO2. PMID:23019310

  9. Cognitive tasks during walking affect cerebral blood flow signal features in middle cerebral arteries and their correlation to gait characteristics.

    PubMed

    Gatouillat, Arthur; Bleton, Héloïse; VanSwearingen, Jessie; Perera, Subashan; Thompson, Scott; Smith, Traci; Sejdić, Ervin

    2015-09-26

    Gait is a complex process involving both cognitive and sensory ability and is strongly impacted by the environment. In this paper, we propose to study of the impact of a cognitive task during gait on the cerebral blood flow velocity, the blood flow signal features and the correlation of gait and blood flow features through a dual task methodology. Both cerebral blood flow velocity and gait characteristics of eleven participants with no history of brain or gait conditions were recorded using transcranial Doppler on mid-cerebral artery while on a treadmill. The cognitive task was induced by a backward counting starting from 10,000 with decrement of 7. Central blood flow velocity raw and envelope features were extracted in both time, frequency and time-scale domain; information-theoretic metrics were also extracted and statistical significances were inspected. A similar feature extraction was performed on the stride interval signal. Statistical differences between the cognitive and baseline trials, between the left and right mid-cerebral arteries signals and the impact of the antropometric variables where studied using linear mixed models. No statistical differences were found between the left and right mid-cerebral arteries flows or the baseline and cognitive state gait features, while statistical differences for specific features were measured between cognitive and baseline states. These statistical differences found between the baseline and cognitive states show that cognitive process has an impact on the cerebral activity during walking. The state was found to have an impact on the correlation between the gait and blood flow features.

  10. Cerebral proliferative angiopathy: Clinical, angiographic features and literature review

    PubMed Central

    Liu, Peng; Lv, Xianli; Lv, Ming

    2016-01-01

    Purpose Here we present our experience with five cerebral proliferative angiopathy (CPA) patients to better delineate the clinical and angiographic features as well as the treatment selection of this disease. Methods Between October 2008 and October 2012, five consecutive patients diagnosed with CPA were admitted to our department in our hospital. All the five patients received magnetic resonance imaging, digital subtraction angiography, and positron emission computed tomography (PET) to definitively confirm this disease. We also collected 15 previously published instances of CPA to analyze the characteristics of this rare entity. Results As to the five patients, three were female and two were male, between the ages of 4 and 52 years with a mean age of 24.8 ± 20.6 years. The PET results showed that perfusion was decreased over the affected hemispheres in all five patients. As to the treatment, only one patient received encephalo-duro-arterio-synangiosis (EDAS) revascularization surgery. The other four patients were conservatively observed. During the follow-up period (range 3–6 years, mean 4 ± 1.9 years), the patient who underwent EDAS surgery manifested relief of clinical symptoms. In the conservative series, the symptoms in two patients aggravated and suffered permanent neurologic deficits. Conclusion CPA is a rare entity. Natural history has showed this disease is not stable and may progress at a certain time point. The EDAS procedure may be a treatment for CPA-related oligemia since there is currently little data and follow-up available. PMID:26472638

  11. Regulation of cerebral metabolism during cortical spreading depression

    PubMed Central

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

    2015-01-01

    We analyzed the metabolic response to cortical spreading depression that drastically increases local energy demand to restore ion homeostasis. During single and multiple cortical spreading depressions in the rat cortex, we simultaneously monitored extracellular levels of glucose and lactate using rapid sampling microdialysis and glucose influx using 18 F-fluorodeoxyglucose positron emission tomography while tracking cortical spreading depression using laser speckle imaging. Combining the acquired data with steady-state requirements we developed a mass-conserving compartment model including neurons and glia that was consistent with the observed data. In summary, our findings are: (1) Early breakdown of glial glycogen provides a major source of energy during increased energy demand and leaves 80% of blood-borne glucose to neurons. (2) Lactate is used solely by neurons and only if extracellular lactate levels are >80% above normal. (3) Although the ratio of oxygen and glucose consumption transiently reaches levels <3, the major part (>90%) of the overall energy supply is from oxidative metabolism. (4) During cortical spreading depression, brain release of lactate exceeds its consumption suggesting that lactate is only a circumstantial energy substrate. Our findings provide a general scenario for the metabolic response to increased cerebral energy demand. PMID:26661217

  12. Hepatic and cerebral energy metabolism after neonatal canine alimentation.

    PubMed

    Kliegman, R M; Miettinen, E L; Morton, S K

    1983-04-01

    Intrahepatic and intracerebral metabolic responses to neonatal fasting or enteric carbohydrate alimentation were investigated among newborn dogs. Pups were either fasted or given an intravenous glucose infusion (alimented) before an enteric feeding of physiologic quantities of either glucose or galactose. These pups were also compared to another group which was completely starved throughout the study period. Gastrointestinal carbohydrate feeding resulted in enhanced hepatic glycogen content among pups after a prior state of fasting. Though there were no differences of glycogen content between glucose or galactose feeding in this previously fasted group, combined intravenous glucose and enteric galactose administration produced the greatest effect on hepatic glycogen synthesis. Intrahepatic fructose 1, 6-diphosphate and phosphoenolpyruvate levels were increased among previously fasted pups fed enteric monosaccharides compared to completely starved control pups, whereas intrahepatic phosphoenolpyruvate and pyruvate levels were elevated after combined intravenous and enteric carbohydrate administration. Of greater interest was the observation that hepatic levels of ATP were significantly elevated among all groups given exogenous carbohydrates compared to the completely starved control group. In contrast to the augmented hepatic glycogen and ATP levels, there were no alterations of cerebral glycogen or ATP after alimentation. Nevertheless, cerebral pyruvate and/or phosphoenolpyruvate concentrations were elevated after enteric or combined intravenous and enteric alimentation compared to the totally starved control pups.

  13. A practical method of serial bedside measurement of cerebral blood flow and metabolism during neurointensive care.

    PubMed Central

    Sharples, P M; Stuart, A G; Aynsley-Green, A; Heaviside, D; Pay, D A; McGann, A; Crawford, P J; Harpin, R; Eyre, J A

    1991-01-01

    Acute encephalopathy is a major cause of death and neurological handicap in children. The principle aims of treatment are to provide adequate cerebral blood flow for the brain's metabolic needs and to prevent intracranial pressure rising above the level at which brain herniation occurs. Rational management requires an understanding of the pathophysiological changes in cerebral blood flow and metabolism which occur. The paucity of data on this subject reflects the perceived difficulty of measuring cerebral blood flow and cerebral metabolism in children. A modification of the Kety Schmidt technique of measuring cerebral blood flow and cerebral metabolism is described. This modification makes it possible to perform serial bedside measurements in children receiving intensive care. This method was used to perform 348 measurements in 58 children. The method was reproducible and no significant complications were encountered. The results indicated that appreciable changes in cerebral blood flow and metabolism could occur in individual patients over time, emphasising the importance of serial measurements. This technique may provide a practical means of monitoring cerebral blood flow and metabolism in very sick children receiving neurointensive care and evaluating the efficacy of treatment. PMID:1755648

  14. Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.

    PubMed Central

    Tedeschi, E; Hasselbalch, S G; Waldemar, G; Juhler, M; Høgh, P; Holm, S; Garde, L; Knudsen, L L; Klinken, L; Gjerris, F

    1995-01-01

    The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series. Images PMID:7500099

  15. Acute hypoxia increases the cerebral metabolic rate – a magnetic resonance imaging study

    PubMed Central

    Lindberg, Ulrich; Aachmann-Andersen, Niels Jacob; Lisbjerg, Kristian; Christensen, Søren Just; Law, Ian; Rasmussen, Peter; Olsen, Niels V; Larsson, Henrik BW

    2015-01-01

    The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O2 hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% (p<10-6), glutamate increased by 4.7% (p<10-4) and creatine and phosphocreatine decreased by 15.2% (p<10-3). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia. PMID:26661163

  16. Age differences in intercorrelations between regional cerebral metabolic rates for glucose

    SciTech Connect

    Horwitz, B.; Duara, R.; Rapoport, S.I.

    1986-01-01

    Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using (18F)fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men.

  17. In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH

    PubMed Central

    Yaseen, Mohammad A.; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A.; Boas, David A.

    2013-01-01

    Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism. PMID:23412419

  18. In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH.

    PubMed

    Yaseen, Mohammad A; Sakadžić, Sava; Wu, Weicheng; Becker, Wolfgang; Kasischke, Karl A; Boas, David A

    2013-02-01

    Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism.

  19. Cerebral Blood Flow and Metabolism in the Wernicke-Korsakoff Syndrome*

    PubMed Central

    Shimojyo, Sadatomo; Scheinberg, Peritz; Reinmuth, Oscar

    1967-01-01

    Cerebral blood flow and metabolism were measured by the iodoantipyrine-4-131I method in nine patients and by the nitrous oxide method in three patients with the Wernicke-Korsakoff syndrome. Cerebral blood flow and cerebral oxygen and glucose consumption were strikingly reduced from the normal, whereas cerebral vascular resistance was increased. Total cerebral metabolism and blood flow may be greatly reduced even though the cerebral metabolic defect is confined to circumscribed anatomical areas. Profound reduction in brain metabolism is not necessarily reflected in alterations of consciousness or awareness as has been previously suggested, or in electroencephalographic abnormalities. This appears to provide cogent support for the neurophysiological principle that disturbance of consciousness is a function of the location of the lesion, not the over-all degree of metabolic defect. The absence of improvement of cerebral metabolic functions in two patients who were restudied after an additional 2 to 3 weeks of treatment confirms the clinical impression of incomplete recovery in many such patients. PMID:6025486

  20. Metabolic Features of Cancer Treatment Resistance.

    PubMed

    Viale, Andrea; Draetta, Giulio F

    A major barrier to achieving durable remission and a definitive cure in oncology patients is the emergence of tumor resistance, a common outcome of different disease types, and independent from the therapeutic approach undertaken. In recent years, subpopulations of slow-cycling cells endowed with enhanced tumorigenic potential and multidrug resistance have been isolated in different tumors, and mounting experimental evidence suggests these resistant cells are responsible for tumor relapse. An in-depth metabolic characterization of resistant tumor stem cells revealed that they rely more on mitochondrial respiration and less on glycolysis than other tumor cells, a finding that challenges the assumption that tumors have a primarily glycolytic metabolism and defective mitochondria. The demonstration of a metabolic program in resistant tumorigenic cells that may be present in the majority of tumors has important therapeutic implications and is a critical consideration as we address the challenge of identifying new vulnerabilities that might be exploited therapeutically.

  1. Selective cerebral perfusion: real-time evidence of brain oxygen and energy metabolism preservation.

    PubMed

    Salazar, Jorge D; Coleman, Ryan D; Griffith, Stephen; McNeil, Jeffrey D; Steigelman, Megan; Young, Haven; Hensler, Bart; Dixon, Patricia; Calhoon, John; Serrano, Faridis; DiGeronimo, Robert

    2009-07-01

    Deep hypothermic circulatory arrest (DHCA) is commonly used for complex cardiac operations in children, often with selective cerebral perfusion (SCP). Little data exist concerning the real-time effects of DHCA with or without SCP on cerebral metabolism. Our objective was to better define these effects, focusing on brain oxygenation and energy metabolism. Piglets undergoing cardiopulmonary bypass were assigned to either 60 minutes of DHCA at 18 degrees C (n = 9) or DHCA with SCP at 18 degrees C (n = 8), using pH-stat management. SCP was administered at 10 mL/kg/min. A cerebral microdialysis catheter was implanted into the cortex for monitoring of cellular ischemia and energy stores. Cerebral oxygen tension and intracranial pressure also were monitored. After DHCA with or without SCP, animals were recovered for 4 hours off cardiopulmonary bypass. With SCP, brain oxygen tension was preserved in contrast to DHCA alone (p < 0.01). Deep hypothermic circulatory arrest was associated with marked elevations of lactate (p < 0.01), glycerol (p < 0.01), and the lactate to pyruvate ratio (p < 0.001), as well as profound depletion of the energy substrates glucose (p < 0.001) and pyruvate (p < 0.001). These changes persisted well into recovery. With SCP, no significant cerebral microdialysis changes were observed. A strong correlation was demonstrated between cerebral oxygen levels and cerebral microdialysis markers (p < 0.001). Selective cerebral perfusion preserves cerebral oxygenation and attenuates derangements in cerebral metabolism associated with DHCA. Cerebral microdialysis provides real-time metabolic feedback that correlates with changes in brain tissue oxygenation. This model enables further study and refinement of strategies aiming to limit brain injury in children requiring complex cardiac operations.

  2. Evaluation of MR derived cerebral oxygen metabolic index in experimental hyperoxic hypercapnia, hypoxia and ischemia

    PubMed Central

    An, Hongyu; Liu, Qingwei; Chen, Yasheng; Lin, Weili

    2009-01-01

    Background and Purpose A non-invasive MRI method to measure cerebral oxygen metabolism has the potential to assess tissue viability during cerebral ischemia. The purposes of this study were 1) to validate MR oxygenation measurements across a wide range of global cerebral oxygenation; and 2) to examine the spatiotemporal evolution of oxygen metabolism during focal middle cerebral artery occlusion (MCAO) in rats. Methods A group of rats (n=28) under normal, hyperoxic hypercapnia and hypoxia were studied to compare MR measured cerebral oxygen saturation (O2SatMRv) with blood gas oximetry measurements in the jugular vein (O2SatJV) and superior sagittal sinus (O2SatSSS). In a separate group of rats (n=31), MR measured cerebral oxygen metabolic index (MR_COMI) was acquired at multiple time-points during MCAO. Histogram analysis was performed on the normalized MR_COMI (rMR_COMI) to examine evolution of oxygen metabolism during acute ischemia. Results Highly linear relationships were obtained between O2SatMRv and O2SatJV/O2SatSSS in rats under global cerebral oxygenation alterations. In the focal ischemia study, rMR_COMI values were significantly lower within the areas of eventual infarction than other regions. Moreover, the rMR_COMI values within the ischemic territory decreased with time, concomitant with an increase in the number of voxels with severely impaired oxygen metabolism. Conclusion Accurate estimates of O2SatMRv can be obtained across a broad and physiologically relevant range of cerebral oxygenation. Furthermore, this method demonstrates a dynamic alteration of cerebral oxygen metabolism during acute ischemia in rats. PMID:19359642

  3. Regional cerebral brain metabolism correlates of neuroticism and extraversion.

    PubMed

    Deckersbach, Thilo; Miller, Karen K; Klibanski, Anne; Fischman, Alan; Dougherty, Darin D; Blais, Mark A; Herzog, David B; Rauch, Scott L

    2006-01-01

    Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based on the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the amygdala. Twenty healthy women completed an (18F)FDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively.

  4. Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology

    PubMed Central

    Dehaes, Mathieu; Cheng, Henry H.; Buckley, Erin M.; Lin, Pei-Yi; Ferradal, Silvina; Williams, Kathryn; Vyas, Rutvi; Hagan, Katherine; Wigmore, Daniel; McDavitt, Erica; Soul, Janet S.; Franceschini, Maria Angela; Newburger, Jane W.; Ellen Grant, P.

    2015-01-01

    Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi), cerebral oxygen metabolism (CMRO2i) and SO2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO2i and CBFi, which returned to baseline when stable. However, SO2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO2 alone. PMID:26713191

  5. Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy.

    PubMed Central

    Lockwood, A H; Ginsberg, M D; Rhoades, H M; Gutierrez, M T

    1986-01-01

    The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of "threshold" amounts of ammonia were assessed. 8 wk after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ranged from 12 to 18%. Unilateral infusions of ammonia did not affect behavior but altered the electroencephalogram and selectively increased the glucose metabolic rate in the thalamus, hypothalamus, and substantia nigra in half of the animals, a pattern similar to that seen after a portacaval shunt, suggesting hyperammonemia as the cause of postshunt increases in glucose metabolism. Visual inspection of autoradiograms, computed correlation coefficients relating interregional metabolism, and principal component analysis suggest that normal cerebral metabolic and functional interrelationships are altered by shunting. Ammonia stimulation of the hypothalamic satiety centers may suppress appetite and lead to cachexia. Reductions in the ammonia detoxification capacity of skeletal muscle may increase the probability of developing future episodes of hyperammonemia, perpetuating the process. Direct effects of ammonia on specific brain centers such as the dorsomedial hypothalamus and reticular activating system may combine with global disruptions of cerebral metabolic-functional relationships to produce the protean manifestations of portal-systemic encephalopathy. Images PMID:3722388

  6. Metabolic brain imaging correlated with clinical features of brain tumors

    SciTech Connect

    Alavi, J.; Alavi, A.; Dann, R.; Kushner, M.; Chawluk, J.; Powlis, W.; Reivich, M.

    1985-05-01

    Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.

  7. Metabolic features of chronic fatigue syndrome

    PubMed Central

    Naviaux, Robert K.; Naviaux, Jane C.; Li, Kefeng; Bright, A. Taylor; Alaynick, William A.; Wang, Lin; Baxter, Asha; Nathan, Neil; Anderson, Wayne; Gordon, Eric

    2016-01-01

    More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer. PMID:27573827

  8. Metabolic features of chronic fatigue syndrome.

    PubMed

    Naviaux, Robert K; Naviaux, Jane C; Li, Kefeng; Bright, A Taylor; Alaynick, William A; Wang, Lin; Baxter, Asha; Nathan, Neil; Anderson, Wayne; Gordon, Eric

    2016-09-13

    More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21-67 y). Females were 52 (±2.5) y old (range, 20-67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84-100%] in males using eight metabolites and 96% (95% CI, 86-100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

  9. Cerebral blood flow and oxygen metabolism during mild hypothermia in patients with subarachnoid haemorrhage.

    PubMed

    Kawamura, S; Suzuki, A; Hadeishi, H; Yasui, N; Hatazawa, J

    2000-01-01

    Cerebral blood flow and O2 metabolism during hypothermia (33-34 degrees C) was evaluated in 5 patients with aneurysmal subarachnoid haemorrhage by positron emission tomography (PET). Their preoperative clinical condition was WFNS scale IV or V. The patients received surface cooling postoperatively, and were maintained in a hypothermic state during transfer for radiological examination. Positron emission tomography revealed a decrease in cerebral blood flow and O2 metabolic rate. Cerebral blood flow was 34.8+/-15.1 ml/100 ml/min and the O2 metabolic rate was 1.85+/-0.61 ml/100 ml/min in areas of the middle cerebral artery ipsilateral to the ruptured aneurysms, whereas these values were 30.8+/-7.1 and 2.21+/-0.45 ml/100 ml/min, respectively, on the contralateral side. This represents a decrease of 37+/-27% compared to normal cerebral blood flow and 52+/-16% compared to normal O2 metabolic rate (p < 0.02) in the ipsilateral areas, and decreases of 44+/-13% and 43+/-12%, respectively, on the contralateral side. The present results reflected the luxury perfusion state in almost all cases and provide the first PET evidence of decreased cerebral blood flow and metabolic rate of O2 during hypothermia in humans.

  10. Disturbance of oxidative metabolism of glucose in recent human cerebral infarcts

    SciTech Connect

    Wise, R.J.; Rhodes, C.G.; Gibbs, J.M.; Hatazawa, J.; Palmer, T.; Frackowiak, R.S.; Jones, T.

    1983-12-01

    Eight patients with recent cerebral hemispheric infarction were studied with positron emission tomography and the oxygen-15 steady-state inhalation and (18F)deoxyglucose techniques to obtain values of regional cerebral blood flow, oxygen consumption, and glucose metabolism. The Sokoloff equation, used to calculate glucose metabolism, was simplified to exclude the exponential terms containing the rate constants. A value of the lumped constant quoted for normal brain (0.42) was used for infarcted regions and contralateral hemisphere. Mean regional cerebral blood flow, oxygen consumption, and glucose metabolism were all significantly depressed within the infarcts compared with the mirror regions in the contralateral cerebral hemisphere. The mean fractional extraction of oxygen was low, indicating an adequate supply of oxygen for residual oxidative metabolism. Regional oxygen consumption and glucose metabolism were significantly correlated within the infarcts, but with a relationship of 2 moles of oxygen per mole of glucose--one-third that in the contralateral hemisphere and in normal brain. Although these results suggest that the metabolizing tissue of a recent cerebral infarct utilizes aerobic glycolysis, caution about the validity of this pathophysiological observation is dictated by limitations in current positron emission tomographic tracer methodology.

  11. Defective autophagy is a key feature of cerebral cavernous malformations

    PubMed Central

    Marchi, Saverio; Corricelli, Mariangela; Trapani, Eliana; Bravi, Luca; Pittaro, Alessandra; Delle Monache, Simona; Ferroni, Letizia; Patergnani, Simone; Missiroli, Sonia; Goitre, Luca; Trabalzini, Lorenza; Rimessi, Alessandro; Giorgi, Carlotta; Zavan, Barbara; Cassoni, Paola; Dejana, Elisabetta; Retta, Saverio Francesco; Pinton, Paolo

    2015-01-01

    Cerebral cavernous malformation (CCM) is a major cerebrovascular disease affecting approximately 0.3–0.5% of the population and is characterized by enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhages. Cerebral cavernous malformation is a genetic disease that may arise sporadically or be inherited as an autosomal dominant condition with incomplete penetrance and variable expressivity. Causative loss-of-function mutations have been identified in three genes, KRIT1 (CCM1), CCM2 (MGC4607), and PDCD10 (CCM3), which occur in both sporadic and familial forms. Autophagy is a bulk degradation process that maintains intracellular homeostasis and that plays essential quality control functions within the cell. Indeed, several studies have identified the association between dysregulated autophagy and different human diseases. Here, we show that the ablation of the KRIT1 gene strongly suppresses autophagy, leading to the aberrant accumulation of the autophagy adaptor p62/SQSTM1, defective quality control systems, and increased intracellular stress. KRIT1 loss-of-function activates the mTOR-ULK1 pathway, which is a master regulator of autophagy, and treatment with mTOR inhibitors rescues some of the mole-cular and cellular phenotypes associated with CCM. Insufficient autophagy is also evident in CCM2-silenced human endothelial cells and in both cells and tissues from an endothelial-specific CCM3-knockout mouse model, as well as in human CCM lesions. Furthermore, defective autophagy is highly correlated to endothelial-to-mesenchymal transition, a crucial event that contributes to CCM progression. Taken together, our data point to a key role for defective autophagy in CCM disease pathogenesis, thus providing a novel framework for the development of new pharmacological strategies to prevent or reverse adverse clinical outcomes of CCM lesions. PMID:26417067

  12. Defective autophagy is a key feature of cerebral cavernous malformations.

    PubMed

    Marchi, Saverio; Corricelli, Mariangela; Trapani, Eliana; Bravi, Luca; Pittaro, Alessandra; Delle Monache, Simona; Ferroni, Letizia; Patergnani, Simone; Missiroli, Sonia; Goitre, Luca; Trabalzini, Lorenza; Rimessi, Alessandro; Giorgi, Carlotta; Zavan, Barbara; Cassoni, Paola; Dejana, Elisabetta; Retta, Saverio Francesco; Pinton, Paolo

    2015-11-01

    Cerebral cavernous malformation (CCM) is a major cerebrovascular disease affecting approximately 0.3-0.5% of the population and is characterized by enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhages. Cerebral cavernous malformation is a genetic disease that may arise sporadically or be inherited as an autosomal dominant condition with incomplete penetrance and variable expressivity. Causative loss-of-function mutations have been identified in three genes, KRIT1 (CCM1), CCM2 (MGC4607), and PDCD10 (CCM3), which occur in both sporadic and familial forms. Autophagy is a bulk degradation process that maintains intracellular homeostasis and that plays essential quality control functions within the cell. Indeed, several studies have identified the association between dysregulated autophagy and different human diseases. Here, we show that the ablation of the KRIT1 gene strongly suppresses autophagy, leading to the aberrant accumulation of the autophagy adaptor p62/SQSTM1, defective quality control systems, and increased intracellular stress. KRIT1 loss-of-function activates the mTOR-ULK1 pathway, which is a master regulator of autophagy, and treatment with mTOR inhibitors rescues some of the mole-cular and cellular phenotypes associated with CCM. Insufficient autophagy is also evident in CCM2-silenced human endothelial cells and in both cells and tissues from an endothelial-specific CCM3-knockout mouse model, as well as in human CCM lesions. Furthermore, defective autophagy is highly correlated to endothelial-to-mesenchymal transition, a crucial event that contributes to CCM progression. Taken together, our data point to a key role for defective autophagy in CCM disease pathogenesis, thus providing a novel framework for the development of new pharmacological strategies to prevent or reverse adverse clinical outcomes of CCM lesions.

  13. Cerebral circulatory and metabolic effects of 5-hydroxytryptamine in anesthetized baboons.

    PubMed Central

    Harper, M A; MacKenzie, E T

    1977-01-01

    1. The cerebral circulatory effects of the intracarotid administration of 5-hydroxytryptamine were examined in anaesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe technique, cerebral O2 consumption and glucose uptake were measured as indices of brain metabolism and electrocortical activity was continuously monitored. 2. Despite a marked reduction in the calibre of the internal carotid artery (assessed angiographically), the intracarotid infusion of 5-hydroxytryptamine 0-1 microgram/kg. min did not effect any significant changes in cerebral blood flow, O2 consumption or glucose uptake. 3. Following transient osmotic disruption of the blood-brain barrier with the intracarotid infusion of hypertonic urea, the same dose of 5-hydroxytryptamine effected a marked reduction in cerebral blood flow from 51 +/- 2 to 36 +/- 2 ml./100 g. min (mean +/- S.E.; P less than 0-01). Both indices of cerebral metabolism were reduced significantly and the e.e.g. showed a more pronounced suppression-burst pattern. 4. We postulate that the cerebral circulatory responses to 5-hydroxytryptamine are dependent upon the integrity of the blood-brain barrier and the predominant effect of the intravascular administration of 5-hydroxytryptamine is on cortical activity or metabolism, rather than on cerebrovascular smooth muscle. Images Plate 1 PMID:411921

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

    PubMed Central

    Mellendijk, Laura; Wiesmann, Maximilian; 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 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. PMID:26580647

  15. Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates.

    PubMed

    Shellhaas, Renée A; Burns, Joseph W; Wiggins, Stephanie A; Christensen, Mary K; Barks, John D E; Chervin, Ronald D

    2014-04-01

    Among adults, wakefulness and rapid eye movement (REM) sleep, compared to non-REM sleep, require higher overall brain metabolism, but in neonates analogous data are not available. Behavioral states with higher metabolic demand could increase vulnerability to hypoperfusion or hypoxia in the compromised neonatal brain. Using cerebral oximetry (near-infrared spectroscopy), and simultaneous polysomnography, we evaluated whether brain oxygen metabolism varies by sleep-wake state among critically ill newborns. For each of 10 infants, sleep-wake cycling was detectable and cerebral oximetry varied (P < .0001) across behavioral states, but the patterns differed among subjects. We conclude that cerebral oxygen metabolism varies with sleep-wake states in high-risk newborns. The direction and degree of these changes are variable and subject-specific in this initial sample, but could reflect or affect brain injury and vulnerability.

  16. The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans.

    PubMed

    Braz, Igor D; Fisher, James P

    2016-08-15

    Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age-related alterations in cerebral vascular function. During low-to-moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ∼10-30%. Beyond ∼60-70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation-mediated reduction in the partial pressure of arterial carbon dioxide (P aC O2) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial-internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age-related reduction in P aC O2 during exercise by the provision of supplementary CO2 is suggested to remove ∼50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age-related reductions in cerebral perfusion during exercise are partly associated with a lower P aC O2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  17. The micro-architecture of the cerebral cortex: Functional neuroimaging models and metabolism

    PubMed Central

    Riera, Jorge J.; Schousboe, Arne; Waagepetersen, Helle S.; Howarth, Clare; Hyder, Fahmeed

    2014-01-01

    In order to interpret/integrate data obtained with different functional neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward-generative models of a diversity of brain mechanisms at the mesoscopic level are considered necessary. For the cerebral cortex, the brain structure with possibly the most relevance for functional neuroimaging, a variety of such biophysical models has been proposed over the last decade. The development of technological tools to investigate in vitro the physiological, anatomical and biochemical principles at the microscopic scale in comparative studies formed the basis for such theoretical progresses. However, with the most recent introduction of systems to record electrical (e.g. miniaturized probes chronically/acutely implantable in the brain), optical (e.g. two-photon laser scanning microscopy) and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy) signals using living laboratory animals, the field is receiving even greater attention. Major advances have been achieved by combining such sophisticated recording systems with new experimental strategies (e.g. transgenic/knock-out animals, high resolution stereotaxic manipulation systems for probe-guidance and cellular-scale chemical-delivery). Theoreticians may now be encouraged to re-consider previously formulated mesoscopic level models in order to incorporate important findings recently made at the microscopic scale. In this series of reviews, we summarize the background at the microscopic scale, which we suggest will constitute the foundations for upcoming representations at the mesoscopic level. In this first part, we focus our attention on the nerve ending particles in order to summarize basic principles and mechanisms underlying cellular metabolism in the cerebral cortex. It will be followed by two parts highlighting major features in its organization/working-principles to regulate both cerebral blood circulation and neuronal activity, respectively

  18. Metabolic Pattern of the Acute Phase of Subarachnoid Hemorrhage in a Novel Porcine Model: Studies with Cerebral Microdialysis with High Temporal Resolution

    PubMed Central

    Nyberg, Christoffer; Karlsson, Torbjörn; Hillered, Lars; Engström, Elisabeth Ronne

    2014-01-01

    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. PMID:24940881

  19. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia.

    PubMed

    Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

    2014-01-01

    Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

  20. Cerebral glucose metabolism in type I alpha-N-acetylgalactosaminidase deficiency: an infantile neuroaxonal dystrophy.

    PubMed

    Rudolf, J; Grond, M; Schindler, D; Heiss, W D; Desnick, R J

    1999-08-01

    Cerebral glucose metabolism was investigated in a 4.8-year-old boy with alpha-N-acetylgalactosaminidase deficiency using 2-[18F]fluoro-2-deoxy-D-glucose and positron emission tomography (PET). In comparison to normal values for age, the overall cerebral glucose metabolism was reduced and the regional cerebral glucose metabolism was decreased in proportion to the degree of atrophy. In the supratentorial cortical regions, the hypometabolism was asymmetric. However, the level of regional cerebral glucose metabolism in all cortical regions excluded a persistent vegetative state. In the lentiform nucleus and the head of the caudate, comparatively increased regional cerebral glucose metabolism was documented, similar to findings in neurodegenerative disorders with active epilepsy. In contrast, the infratentorial structures (cerebellar hemispheres, brain stem, mesencephalon, and hypothalamus), which are predominantly affected by the atrophic process, showed distinct and symmetric hypometabolism. Thus, the 2-[18F]-fluoro-2-deoxy-D-glucose PET scans provided additional insight into and correlation of the functional and structural disturbances in type I alpha-N-acetylgalactosaminidase deficiency, in addition to documenting the hypometabolism due to brain atrophy.

  1. Hemorrhagic Reversible Cerebral Vasoconstriction Syndrome: Features and Mechanisms.

    PubMed

    Topcuoglu, Mehmet A; Singhal, Aneesh B

    2016-07-01

    To compare hemorrhagic and nonhemorrhagic reversible cerebral vasoconstriction syndromes (RCVS) with a view to understand mechanisms. This single-center retrospective study included 162 patients with RCVS. Clinical, brain imaging, and angiography data were analyzed. The mean age was 44±13 years, 78% women. Hemorrhages occurred in 43% including 21 patients with intracerebral hemorrhage (ICH) and 62 with convexal subarachnoid hemorrhage (cSAH). The frequency of triggers (eg, vasoconstrictive drugs) and risk factors (eg, migraine) were not significantly different between hemorrhagic and nonhemorrhagic RCVS or between subgroups (ICH versus non-ICH, isolated cSAH versus normal scan). Hemorrhagic lesions occurred within the first week, whereas infarcts and vasogenic edema accumulated during 2 to 3 weeks (P<0.001). Although all ICHs occurred before cSAH, their time course was not significantly different (P=0.11). ICH and cSAH occurred earlier than infarcts (P≤0.001), and ICH earlier than vasogenic edema (P=0.009). Angiogram analysis showed more severe vasoconstriction in distal versus proximal segments in all lesion types (ICH, cSAH, infarction, vasogenic edema, and normal scan). The isolated infarction group had more severe proximal vasoconstriction, and those with normal imaging had significantly less vasoconstriction. Multivariable analysis failed to uncover independent predictors of hemorrhagic RCVS; however, female sex predicted ICH (P=0.048), and angiographic severity predicted infarction (P=0.043). ICH and cSAH are common complications of RCVS. Triggers and risk factors do not predict lesion subtype but may alter central vasomotor control mechanisms resulting in centripetal angiographic evolution. Early distal vasoconstriction is associated with lobar ICH and cSAH, and delayed proximal vasoconstriction with infarction. © 2016 American Heart Association, Inc.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  5. Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease.

    PubMed

    Esmaeilzadeh, Mouna; Kullingsjö, Johan; Ullman, Henrik; Varrone, Andrea; Tedroff, Joakim

    2011-01-01

    Huntington disease is a hereditary neurodegenerative disorder resulting in loss of motor, cognitive, and behavioral functions and is characterized by a distinctive pattern of cerebral metabolic abnormalities. Pridopidine (ACR16) belongs to a novel class of central nervous system compounds in development for the treatment of Huntington disease. The objective of the study was to investigate the metabolic changes in patients with Huntington disease before and after pridopidine treatment. [(18)F]Fluorodeoxyglucose positron emission tomographic imaging was used to measure the regional cerebral metabolic rate of glucose at baseline and after 14 days of open-label pridopidine treatment in 8 patients with Huntington disease. Clinical assessments were performed using the Unified Huntington's Disease Rating Scale. Statistical parametric mapping analysis showed increased metabolic activity in several brain regions such as the precuneus and the mediodorsal thalamic nucleus after treatment. In addition, after pridopidine treatment, the correlation between the clinical status and the cerebral metabolic activity was strengthened. Our findings suggest that pridopidine induces metabolic changes in brain regions implicated as important for mediating compensatory mechanisms in Huntington disease. In addition, the finding of a strong relationship between clinical severity and metabolic activity after treatment also suggests that pridopidine treatment targets a Huntington disease-related metabolic activity pattern.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  9. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography

    SciTech Connect

    Wolkin, A.; Jaeger, J.; Brodie, J.D.; Wolf, A.P.; Fowler, J.; Rotrosen, J.; Gomez-Mont, F.; Cancro, R.

    1985-05-01

    Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities.

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

    SciTech Connect

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. )

    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.

  11. Cerebral energy metabolism, glucose transport and blood flow: changes with maturation and adaptation to hypoglycaemia.

    PubMed

    Nehlig, A

    1997-02-01

    Brain maturation is characterized by a peak of cerebral energy metabolism and blood flow occurring between 3 and 8 years of age in humans and around 14-17 days of postnatal life in rats. This high activity coincides with the period of active brain growth. The human brain is dependent on glucose alone during that period, whereas rat brain uses both glucose and ketone bodies to cover its energetic and biosynthetic needs. The maturation of the density of glucose transporter sites-GLUT1 located at the blood-brain barrier and GLUT3 at the neuronal membrane-parallels the development of cerebral glucose utilization. During moderate acute hypoglycaemia, there are no changes in cerebral functional activity; cerebral glucose utilization decreases and blood flow increases only when hypoglycaemia is severe (lower than 2 mumol/ml). During chronic hypoglycaemia, the brain adapts to the low circulating levels of glucose: the number of glucose transporter sites is increased, and cerebral glucose utilization and function are maintained at normal levels while cerebral blood flow is more moderately increased than during acute hypoglycaemia. Neuronal damage consecutive to severe and prolonged hypoglycaemia occurs mainly in the cerebral cortex, hippocampus and caudate-putamen as a result of active release of excitatory amino acids.

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

    ERIC Educational Resources Information Center

    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)

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

    NASA Astrophysics Data System (ADS)

    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.

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

    ERIC Educational Resources Information Center

    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)

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

    PubMed

    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.

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

    PubMed Central

    Prins, Mayumi L.; Matsumoto, Joyce H.

    2014-01-01

    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. PMID:24721741

  17. Eccentric target sign in cerebral toxoplasmosis: neuropathological correlate to the imaging feature.

    PubMed

    Kumar, G G Sharath; Mahadevan, A; Guruprasad, A S; Kovoor, Jerry M E; Satishchandra, P; Nath, Avindra; Ranga, Udaykumar; Shankar, S K

    2010-06-01

    Cerebral toxoplasmosis remains one of the most common focal brain lesions in patients with acquired immune deficiency syndrome (AIDS). Diagnosis is a challenge because on cranial imaging it closely mimics central nervous system lymphoma, primary and metastatic central nervous system (CNS) tumors, or other intracranial infections like tuberculoma or abscesses. A magnetic resonance imaging (MRI) feature on postcontrast T1-weighted sequences considered pathognomonic of toxoplasmosis is the "eccentric target sign." The pathological correlate of this imaging sign has been speculative. Herein we correlate the underlying histopathology to the MR feature of eccentric target sign in a patient with autopsy-proven HIV/AIDS-related cerebral toxoplasmosis. The central enhancing core of the target seen on MRI was produced by a leash of inflamed vessels extending down the length of the sulcus that was surrounded by concentric zones of necrosis and a wall composed of histiocytes and proliferating blood vessels, with impaired permeability producing the peripheral enhancing rim.

  18. Eccentric Target Sign in Cerebral Toxoplasmosis – neuropathological correlate to the imaging feature

    PubMed Central

    Sharath Kumar, GG; Mahadevan, A; Guruprasad, AS; Kovoor, Jerry ME; Satishchandra, P; Nath, Avindra; Kumar, Ranga Uday; Shankar, SK

    2010-01-01

    Cerebral toxoplasmosis remains one of the most common focal brain lesions in patients with acquired immune deficiency syndrome (AIDS). Diagnosis is a challenge as on cranial imaging, it closely mimics central nervous system lymphoma, primary and metastatic CNS tumors or other intracranial infections like tuberculoma or abscesses. An MR imaging feature on post contrast T1 weighted sequences considered pathognomonic of toxoplasmosis is the ‘eccentric target sign’. The pathological correlate of this imaging sign has been speculative. Herein we correlate the underlying histopathology to the MR feature of ‘eccentric target sign’ in a patient with autopsy proven HIV/AIDS related cerebral toxoplasmosis. The central enhancing core of the target seen on MR imaging was produced by a leash of inflamed vessels extending down the length of sulcus that was surrounded by concentric zones of necrosis and a wall composed of histiocytes and proliferating blood vessels with impaired permeability producing the peripheral enhancing rim. PMID:20512900

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

    PubMed

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

    2017-04-01

    Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO2 +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO2 +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

    Madsen, P L; Schmidt, J F; Wildschiødtz, G; Friberg, L; Holm, S; Vorstrup, S; Lassen, N A

    1991-06-01

    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. Contrary to the only previous study in humans, which reported an insignificant 3% reduction in CMRO2 during sleep, we found a deep-sleep-associated statistically highly significant 25% decrease in CMRO2, a magnitude of depression according with studies of glucose uptake and reaching levels otherwise 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.

  1. Mechanisms of murine cerebral malaria: Multimodal imaging of altered cerebral metabolism and protein oxidation at hemorrhage sites

    PubMed Central

    Hackett, Mark J.; Aitken, Jade B.; El-Assaad, Fatima; McQuillan, James A.; Carter, Elizabeth A.; Ball, Helen J.; Tobin, Mark J.; Paterson, David; de Jonge, Martin D.; Siegele, Rainer; Cohen, David D.; Vogt, Stefan; Grau, Georges E.; Hunt, Nicholas H.; Lay, Peter A.

    2015-01-01

    Using a multimodal biospectroscopic approach, we settle several long-standing controversies over the molecular mechanisms that lead to brain damage in cerebral malaria, which is a major health concern in developing countries because of high levels of mortality and permanent brain damage. Our results provide the first conclusive evidence that important components of the pathology of cerebral malaria include peroxidative stress and protein oxidation within cerebellar gray matter, which are colocalized with elevated nonheme iron at the site of microhemorrhage. Such information could not be obtained previously from routine imaging methods, such as electron microscopy, fluorescence, and optical microscopy in combination with immunocytochemistry, or from bulk assays, where the level of spatial information is restricted to the minimum size of tissue that can be dissected. We describe the novel combination of chemical probe–free, multimodal imaging to quantify molecular markers of disturbed energy metabolism and peroxidative stress, which were used to provide new insights into understanding the pathogenesis of cerebral malaria. In addition to these mechanistic insights, the approach described acts as a template for the future use of multimodal biospectroscopy for understanding the molecular processes involved in a range of clinically important acute and chronic (neurodegenerative) brain diseases to improve treatment strategies. PMID:26824064

  2. Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism.

    PubMed

    Dawson, Neil; Ferrington, Linda; Olverman, Henry J; Harmar, Anthony J; Kelly, Paul A T

    2009-08-01

    Polymorphic variation in the human serotonin transporter (SERT; 5-HTT) gene resulting in a lifelong increase in SERT expression is associated with reduced anxiety and a reduced risk of affective disorder. Evidence also suggests that sex influences the effect of this polymorphism on affective functioning. Here we use novel transgenic mice overexpressing human SERT (hSERT OVR) to investigate the possible influence of sex on the alterations in SERT protein expression and cerebral function that occur in response to increased SERT gene transcription. SERT binding levels were significantly increased in the brain of hSERT OVR mice in a region-dependent manner. The increased SERT binding in hSERT OVR mice was more pronounced in female than in male mice. Cerebral metabolism, as reflected by a quantitative index of local cerebral glucose utilization (iLCMRglu), was significantly decreased in many brain regions in hSERT OVR female as compared with wild-type female mice, whereas there was no evidence for a significant effect in any region in males. The ability of hSERT overexpression to modify cerebral metabolism was significantly greater in females than in males. This effect was particularly pronounced in the medial striatum, globus pallidus, somatosensory cortex, mamillary body, and ventrolateral thalamus. Overall, these findings demonstrate that the influence of a lifelong increase in SERT gene transcription on cerebral function is greater in females than in males and may relate, in part, to the influence of sex on genetically driven increases in SERT protein expression.

  3. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study

    PubMed Central

    Park, So Hyeon; Park, Hyun Soo

    2016-01-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders. PMID:27574485

  4. Cerebral energy metabolism following fluid-percussion brain injury in cats.

    PubMed

    Unterberg, A W; Andersen, B J; Clarke, G D; Marmarou, A

    1988-04-01

    Clinical and experimental evidence suggests that head injury can cause alterations of cerebral energy metabolism. However, the etiology of this metabolic perturbation is not known. The objective of this study was to determine the effect of fluid-percussion trauma on cerebral energy metabolism. Seven ventilated, chloralose-anesthetized cats were subjected to a 3.2-atm fluid-percussion brain injury. Before and for 8 hours after trauma, continuous phosphorus-3 1 magnetic resonance spectrography was obtained to noninvasively monitor tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi) levels. Measurement of cerebral blood flow (CBF) by the radioactive microsphere technique and calculation of oxygen and glucose consumption (CMRO2 and CMRG1) were also performed before trauma as well as 30 minutes and 1, 2, 4, and 8 hours after trauma. The data showed a moderate decrease in tissue pH from 7.04 to 6.89 at 30 minutes following trauma with return to control levels by 3 hours posttrauma. During the 8-hour observation period, CBF, CMRO2, and CMRG1 remained at control levels. Tissue PCr and Pi levels were also unchanged. Fluid-percussion trauma at the 3.2-atm level in ventilated cats causes a moderate and transient decrease in tissue pH that returns to control levels after trauma. No other metabolic changes are seen later than 30 minutes posttrauma. This indicates that a mild metabolic disturbance occurs after trauma in the ventilated animal and quickly returns to normal.

  5. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study.

    PubMed

    Park, So Hyeon; Park, Hyun Soo; Kim, Sang Eun

    2016-08-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after (18)F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders.

  6. Clinical and metabolic features of urolithiasis and microlithiasis in children.

    PubMed

    Alpay, Harika; Ozen, Ahmet; Gokce, Ibrahim; Biyikli, Nese

    2009-11-01

    We evaluated the clinical, radiological and metabolic features of 162 children with urolithiasis or microlithiasis who had been referred to our pediatric nephrology clinics between 1998 and 2008 with suspected urolithiasis. The medical histories of these children (78 girls, 84 boys), who ranged in age from 2 months to 16 years (mean age 5.59 +/- 0.35 years), were reviewed retrospectively for clinical and metabolic features of urinary tract calculi. Urinary tract infections (UTI) were present in 45.9% of the cases. The most common presenting symptoms were flank pain or restlessness (25.3%) and hematuria (21.6%), followed by UTI (16%), whereas 23.5% of the cases were detected incidentally during evaluation for other medical conditions. Other symptoms at presentation included dysuria, passing stones, penile edema, enuresis, vomiting and anorexia. Urine analysis revealed metabolic abnormalities in 87% of the cases, including hypercalciuria (33.8%), hypocitraturia (33.1%), hyperoxaluria (26.5%), hyperuricosuria (25.4%), hypocitraturia + hypercalciuria (21.1%), hyperphosphaturia (20.8%) and cystinuria (5.7%). Almost 50% of the patients had a positive family history for urolithiasis. The most frequently involved site was in the kidneys (86%). Ureters and bladder were involved in 12 and 2% of the cases, respectively. A family history of urolithiasis, presenting symptoms and underlying metabolic abnormalities were similar for microlithiasis and the patients with larger stones. However, in our study population, microlithiasis was mainly a disease of young infants, with a greater chance for remission and often not associated with structural changes. The presenting symptoms of urolithiasis show a wide spectrum, so that a high index of suspicion is important for early detection. A metabolic abnormality can be identified in 87% of cases of urolithiasis. Detection of microlithiasis may explain a number of symptoms, thus reducing invasive diagnostic procedures and allowing early

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

    PubMed Central

    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 < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA Vmean, and cerebral vascular conductance index (MCA Vmean/MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO2 (by ∼30 μmol (100 g−1) min−1), and decreases in OCI (by ∼1.5) and (by ∼10 mmHg) during 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

  8. Tissue-dependent cerebral energy metabolism in adolescents with bipolar disorder.

    PubMed

    Dudley, Jonathan; DelBello, Melissa P; Weber, Wade A; Adler, Caleb M; Strakowski, Stephen M; Lee, Jing-Huei

    2016-02-01

    To investigate tissue-dependent cerebral energy metabolism by measuring high energy phosphate levels in unmedicated adolescents diagnosed with bipolar I disorder. Phosphorus-31 magnetic resonance spectroscopic imaging data were acquired over the entire brain of 24 adolescents with bipolar I disorder and 19 demographically matched healthy comparison adolescents. Estimates of phosphocreatine (PCr) and adenosine triphosphate (ATP, determined from the γ-resonance) in homogeneous gray and white matter in the right and left hemispheres of the cerebrum of each subject were obtained by extrapolation of linear regression analyses of metabolite concentrations vs. voxel gray matter fractions. Multivariate analyses of variance showed a significant effect of group on high energy phosphate concentrations in the right cerebrum (p=0.0002) but not in the left (p=0.17). Post-hoc testing in the right cerebrum revealed significantly reduced concentrations of PCr in gray matter and ATP in white matter in both manic (p=0.002 and 0.0001, respectively) and euthymic (p=0.004 and 0.002, respectively) bipolar I disorder subjects relative to healthy comparisons. The small sample sizes yield relatively low statistical power between manic and euthymic groups; cross-sectional observations limit the ability to determine if these findings are truly independent of mood state. Our results suggest bioenergetic impairment - consistent with downregulation of creatine kinase - is an early pathophysiological feature of bipolar I disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Argon does not affect cerebral circulation or metabolism in male humans.

    PubMed

    Grüne, Frank; Kazmaier, Stephan; Hoeks, Sanne Elisabeth; Stolker, Robert Jan; Coburn, Marc; Weyland, Andreas

    2017-01-01

    Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia.

  10. Cerebral glucose metabolic differences in patients with panic disorder

    SciTech Connect

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

    1990-08-01

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

  11. MR image features predicting hemorrhagic transformation in acute cerebral infarction: a multimodal study.

    PubMed

    Liu, Chunming; Dong, Zhengchao; Xu, Liang; Khursheed, Aiman; Dong, Longchun; Liu, Zhenxing; Yang, Jun; Liu, Jun

    2015-11-01

    The aims of this study were to observe magnetic resonance imaging (MRI) features and the frequency of hemorrhagic transformation (HT) in patients with acute cerebral infarction and to identify the risk factors of HT. We first performed multimodal MRI (anatomical, diffusion weighted, and susceptibility weighted) scans on 87 patients with acute cerebral infarction within 24 hours after symptom onset and documented the image findings. We then performed follow-up examinations 3 days to 2 weeks after the onset or whenever the conditions of the patients worsened within 3 days. We utilized univariate statistics to identify the correlations between HT and image features and used multivariate logistical regression to correct for confounding factors to determine relevant independent image features of HT. HT was observed in 17 out of total 87 patients (19.5 %). The infarct size (p = 0.021), cerebral microbleeds (CMBs) (p = 0.004), relative apparent diffusion (rADC) (p = 0.023), and venous anomalies (p = 0.000) were significantly related with HT in the univariate statistics. Multivariate analysis demonstrated that CMBs (odd ratio (OR) = 0.082; 95 % confidence interval (CI) = 0.011-0.597; p = 0.014), rADC (OR = 0.000; 95 % CI = 0.000-0.692; p = 0.041), and venous anomalies (OR = 0.066; 95 % CI = 0.011-0.403; p = 0.003) were independent risk factors for HT. The frequency of HT is 19.5 % in this study. CMBs, rADC, and venous anomalies are independent risk factors for HT of acute cerebral infarction.

  12. Alleviation of Brain Injury-Induced Cerebral Metabolic Depression by Amphetamine: A Cytochrome Oxidase Histochemistry Study

    PubMed Central

    Sutton, Richard L.; Hovda, David A.; Chen, Michael J.; Feeney, Dennis M.

    2000-01-01

    Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and ,he administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of II subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilaterai to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans. PMID:10709218

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

    PubMed Central

    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, 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, we review state

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

    PubMed

    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

  15. Cerebral hemodynamic and metabolic changes caused by brain retraction after aneurysmal subarachnoid hemorrhage.

    PubMed

    Yundt, K D; Grubb, R L; Diringer, M N; Powers, W J

    1997-03-01

    The cerebral hemodynamic and metabolic effects of aneurysmal subarachnoid hemorrhage are complex. To investigate the impact of surgical retraction, we analyzed position emission tomography (PET) studies that measured the regional cerebral metabolic rate for oxygen, regional oxygen extraction fraction, and regional cerebral blood flow in four patients before and after right frontotemporal craniotomies for clipping of ruptured anterior circulation aneurysms. Preoperative studies were conducted 1 day before surgery and postoperative studies 6 to 17 days after surgery. No patient had hydrocephalus or intracerebral hematoma. At the time of the second PET study, none of the patients had signs of clinical vasospasm. Regional measurements were obtained from the right ventrolateral frontal and anterior temporal regions corresponding to the area of retraction and compared to the same regions in the opposite hemisphere. To establish a quantitative means to differentiate between hemodynamic and metabolic changes related to arterial vasospasm and those caused by brain retraction, we studied a second group of preoperative patients, who had undergone PET during angiographic and clinical vasospasm. There was a 45% reduction in regional cerebral metabolic rate for oxygen (1.87 +/- 0.22 to 1.04 +/- 0.28 ml 100 g-1 min-1) and 32% reduction in regional oxygen extraction fraction (0.41 +/- 0.04 to 0.28 +/- 0.03) in the region of retraction but no change in the opposite hemisphere (paired t test; P = 0.042 and 0.003, respectively). There was no change in regional cerebral blood flow in any region. Brain retraction produced a focal area of tissue injury at the site of retractor blade placement, as compared to more diffuse vascular territory changes produced by vasospasm. This reduction in the cerebral metabolic rate of oxygen and the oxygen extraction fraction indicates a primary reduction in metabolism and uncoupling of flow and metabolism (luxury perfusion). Similar findings of luxury

  16. Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I

    PubMed Central

    2014-01-01

    Background Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. Results Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood–brain barrier breakdown was associated with displacement of tight-junction protein Occludin. Conclusion Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke. PMID:24468193

  17. Relationship between relative cerebral blood flow, relative cerebral blood volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal brain.

    PubMed

    Nourhashemi, Mina; Kongolo, Guy; Mahmoudzadeh, Mahdi; Goudjil, Sabrina; Wallois, Fabrice

    2017-04-01

    The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen ([Formula: see text]), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and [Formula: see text] in preterms may, therefore, help to elucidate the principles of cortical hemodynamics during development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see text] by two independent acquisition systems: diffuse correlation spectroscopy and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and 35 weeks of gestational age. Transfer entropy was calculated in order to determine the directionality between rCBF-rCBV and [Formula: see text]. The surrogate method was applied to determine statistical significance. The results show that rCBV and [Formula: see text] have a predominant driving influence on rCBF at the resting state in the preterm neonatal brain. Statistical analysis robustly detected the correct directionality of rCBV on rCBF and [Formula: see text] on rCBF. This study helps to clarify the early organization of the rCBV-rCBF and [Formula: see text] inter-relationship in the immature cortex.

  18. Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy

    PubMed Central

    Weissenborn, Karin; Ahl, Björn; Fischer‐Wasels, Daniela; van den Hoff, Joerg; Hecker, Hartmut; Burchert, Wolfgang; Köstler, Herbert

    2007-01-01

    Background Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy. Methods 13N‐ammonia and 18F‐fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0–1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex. Results A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated. Conclusion Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy. PMID:17660226

  19. Cerebral metabolism during experimental endotoxin shock and after preconditioning with monophosphoryl lipid A.

    PubMed

    Ditz, Claudia; Bahlmann, Ludger; Klaus, Stephan; Keck, Alexander; Onken, Nils; Gliemroth, Jan

    2014-11-01

    Preconditioning with low doses of monophosphoryl lipid A (MPL) has been shown to induce endotoxin tolerance and to reduce the metabolic and hemodynamic consequences of endotoxin shock. However, no data are available about the effects of endotoxin preconditioning on cerebral metabolism during endotoxemia. The study was designed to determine the effects of endotoxin preconditioning with MPL on cerebral metabolism via microdialysis compared to muscle tissue metabolism during experimental endotoxemia. In a controlled animal study, continuous endotoxin infusion (1μg/kg b.w. per h) was administrated to 7 female mixed-breed pigs after pretreatment with MPL in incremental doses of endotoxin during days 5-2 before the experiments. In the control group, 7 animals received a saline pretreatment. In addition to hemodynamic monitoring and blood gas analyses, interstitial lactate, pyruvate, glucose and glycerol concentrations in muscle and cerebral tissue were measured using in vivo microdialysis. There were no significant differences between the two groups with respect to hemodynamic parameters, while mixed venous oxygen saturation (SvO2), arterial blood pH and mean pulmonary arterial pressure (MPAP) were significantly higher in the preconditioned group. Cerebral perfusion pressure (CPP) and brain tissue oxygen pressure (ptiO2) values stayed stable throughout the experiment with no inter-group differences. While interstitial concentrations of lactate and glycerol as well as the lactate/pyruvate (LP) and the lactate/glucose (LG) ratio in muscle tissues were significantly increased in control animals compared to those who had been pretreated with MPL; the results of cerebral microdialysis showed no significant changes in interstitial lactate or glycerol levels in both groups. However, the lactate/glucose (LG) ratio in the control group showed a significantly higher increase than in the preconditioned group. Preconditioning with low doses of MPL ameliorates the negative metabolic

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

    PubMed

    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

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

    PubMed

    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.

  2. Bone Metabolism in Cerebral Palsy and the Effect of Light-Emitting Diode (LED) Irradiation

    PubMed Central

    Yamamoto, Kengo; Ohshiro, Toshio; Ohshiro, Takafumi

    2012-01-01

    In recent years, through the availability of examination by bone metabolism markers, diagnosis and treatment for osteoporosis in elderly people has been greatly advanced. However, bone metabolism in cases of cerebral palsy has not been fully examined. Though children with cerebral palsy tend to be susceptible to insufficiency fractures, a method of treatment for insufficiency fractures has not been established. In the longitudinal progress of bone metabolism, although there was a difference depending on the severity, reduced bone resorption tended to be mild but osteo-genesis tended to decrease in the severe cases. Osteogenesis and bone resorption markers decreased at around ages 8 and 15. The bone resorption marker maintained mild advancement after age 15. With LED irradiation, all of IGF-1, ucOC, osteogenic marker; BAP, and urinary bone resorption marker; NTx/Cr showed a tendency to normalize. In particular, IGF-1, BAP, and NTx/Cr increased significantly one month after irradiation, compared to the non-irradiation group. Bone density assessed by the DIP method showed no apparent change in the short term either. Irradiation by a commercial LED light bulb indicated a possible positive effect on bone metabolism for children with severe cerebral palsy. PMID:24610978

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

    SciTech Connect

    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.

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

    PubMed

    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.

  5. The temporal profile of cerebral blood flow and tissue metabolites indicates sustained metabolic depression after experimental subarachnoid hemorrhage in rats.

    PubMed

    Westermaier, Thomas; Jauss, Alina; Eriskat, Jörg; Kunze, Ekkehard; Roosen, Klaus

    2011-01-01

    Derangement of cerebral metabolism occurs after various insults such as ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). To investigate the course of cerebral blood flow and metabolic parameters in the first hours after experimental SAH. Sixteen Sprague-Dawley rats were subjected to SAH using the endovascular filament model or served as controls (8 rats in each group). Local cerebral blood flow and intracranial pressure were measured continuously. Microdialysis samples were acquired in 30-minute intervals for 6 hours after SAH. Concentrations of glucose, lactate, pyruvate, and glutamate were determined. After induction of SAH, cerebral perfusion pressure and local cerebral blood flow sharply decreased. The decrease in local cerebral blood flow exceeded the decrease in cerebral perfusion pressure throughout the observation period. Glutamate concentrations in microdialysis samples increased sixfold and recovered to baseline levels. Lactate concentrations immediately increased after SAH, recovered incompletely, and remained above the levels of control animals until the end of the sampling period. Pyruvate concentrations showed a delayed increase starting 2 hours after SAH. The course of cerebral blood flow after SAH resembles global ischemia followed by a continuous low-flow state caused by a sudden decrease in cerebral perfusion pressure and acute vasoconstriction. The courses of lactate and pyruvate concentrations indicate a persistently deranged aerobic metabolism.

  6. The habenula and iron metabolism in cerebral mouse models of multiple sclerosis

    PubMed Central

    Sands, Scott A.; Tsau, Sheila; LeVine, Steven M.

    2015-01-01

    Iron accumulates in the CNS of patients with multiple sclerosis, but our understanding of the mechanism accounting for this accumulation is unclear. Mouse models of cerebral experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mice were used together with a histochemical stain for iron and immunohistochemical stains for transferrin receptor, synaptophysin, iron regulatory protein 1 (IRP1) and/or IRP2 to investigate the role of disease activity on CNS iron metabolism. The expression of transferrin receptor, but not IRP1 or IRP2, increased in the medial habenula, which is adjacent to the third ventricle, in response to both types of cerebral EAE. In the habenula, the elevated expression of transferrin receptor in C57BL/6 mice with cerebral EAE was generally restricted to the medial habenula while the expression in SJL mice with cerebral EAE was more diffusely expressed. Iron levels were increased in all regions of the habenula in C57BL/6 mice with cerebral EAE, and in the medial and medial lateral but not the lateral habenula in SJL mice with cerebral EAE. Synaptophysin, which has been observed previously in endocytic vesicles together with the transferrin receptor, was concentrated at the medial habenula, but its levels did not increase with disease in C57BL/6 mice with cerebral EAE. Our results support the model that the medial habenula responds to disease activity by upregulating transferrin receptor to facilitate the movement of iron into the brain from the third ventricle, raising the possibility that a similar mechanism accounts for iron accumulation in deep gray matter structures in patients with multiple sclerosis. PMID:26362814

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

    PubMed

    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.

  8. Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions

    PubMed Central

    Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro

    2017-01-01

    The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions. PMID:28700720

  9. Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions.

    PubMed

    Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro; Rey, Beatriz

    2017-01-01

    The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.

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

    PubMed Central

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

    2007-01-01

    Glucose is the obligate energetic fuel for the mammalian brain and most studies of cerebral energy metabolism assume that the vast majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter proteins (GLUTs) deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters: MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis (Pellerin and Magistretti, 1994) suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, i.e. capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and GLUT3 in BBB endothelial cells, astrocytes and neurons, along with the corresponding kinetic properties of the monocarboxylate transporters, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed upon neuronal activation. PMID:17579656

  11. Overuse of paracetamol caffeine aspirin powders affects cerebral glucose metabolism in chronic migraine patients.

    PubMed

    Di, W; Shi, X; Zhu, Y; Tao, Y; Qi, W; Luo, N; Xiao, Z; Yi, C; Miao, J; Zhang, A; Zhang, X; Fang, Y

    2013-04-01

    Overuse of analgesic plays a prominent role in migraine chronification. Paracetamol caffeine aspirin (PCA) powders are commonly used in Chinese migraineurs. This study investigated the effects of the specific combination analgesic on cerebral glucose metabolism in chronic migraine (CM). 18F-FDG-PET was used to measure regional metabolism in all subjects. Brain metabolisms of CM patients with analgesic overuse (AO-CM; n=10), no analgesic overuse (NAO-CM; n=10), and no regimen (NR-CM; n=10) and 17 age- and gender-matched normal controls (NC) were compared using statistical parametric mapping. Then, all patients underwent brain MRI analysis within 7 days after PET scans, as well as MMSE and MoCA scale for cognitive function tests. Glucose metabolic changes in CM patients taking different dosage of analgesic during headache-free periods and clear distinctions in several brain regions were observed. Patients with AO-CM exhibited significant metabolic reductions in thalamus, as well as increased metabolism in middle temporal gyrus and insula relative to NR-CM and NAO-CM. However, in these regions, no difference was observed in AO-CM except for increased metabolism in the right insula relative to NC group. Overusing PCA powders affects regional brain glucose metabolism in CM. Increased metabolism in the right insula may be associated with recurrently overusing of PCA powders. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  12. The regional cerebral blood flow changes in major depressive disorder with and without psychotic features.

    PubMed

    Gonul, Ali Saffet; Kula, Mustafa; Bilgin, Arzu Guler; Tutus, Ahmet; Oguz, Aslan

    2004-09-01

    Depressive patients with psychotic features demonstrate distinct biological abnormalities in the hypothalamic-pituitary-adrenal axis (HPA), dopaminergic activity, electroencephalogram sleep profiles and measures of serotonergic function when compared to nonpsychotic depressive patients. However, very few functional neuroimaging studies were specifically designed for studying the effects of psychotic features on neuroimaging findings in depressed patients. The objective of the present study was to compare brain Single Photon Emission Tomography (SPECT) images in a group of unmedicated depressive patients with and without psychotic features. Twenty-eight patients who fully met DSM-IV criteria for major depressive disorder (MDD, 12 had psychotic features) were included in the study. They were compared with 16 control subjects matched for age, gender and education. Both psychotic and nonpsychotic depressed patients showed significantly lower regional cerebral blood flow (rCBF) values in the left and right superior frontal cortex, and left anterior cingulate cortex compared to those of controls. In comparison with depressive patients without psychotic features (DwoPF), depressive patients with psychotic features (DwPF) showed significantly lower rCBF perfusion ratios in left parietal cortex, left cerebellum but had higher rCBF perfusion ratio in the left inferior frontal cortex and caudate nucleus. The present study showed that DwPF have a different rCBF pattern compared to patients without psychotic features. Abnormalities involving inferior frontal cortex, striatum and cerebellum may play an important role in the generation of psychotic symptoms in depression.

  13. Radioactive oxygen-15 in the study of cerebral blood flow, blood volume, and oxygen metabolism

    SciTech Connect

    Ter-Pogossian, M.M.; Herscovitch, P.

    1985-10-01

    The short half-life of /sup 15/O led early observers to believe that it was unsuitable for use as a biological tracer. However, initial studies with this nuclide demonstrated its potential usefulness for in vivo, regional physiologic measurements. Subsequently, techniques were developed to measure cerebral blood flow (CBF), blood volume, and oxygen metabolism using intracarotid injection of /sup 15/O-labeled radiopharmaceuticals and highly collimated scintillation probes to record the time course of radioactivity in the brain. The development of positron emission tomography (PET) made possible the in vivo, noninvasive measurement of the absolute concentration of positron-emitting nuclides. A variety of tracer kinetic models were formulated to obtain physiologic measurements from tomographic images of the distribution of 15O-labeled radiopharmaceuticals in the brain. Regional cerebral oxygen metabolism is measured using scan data obtained following the inhalation of /sup 15/O-labeled oxygen. The tracer kinetic models used to measure rCBV, blood flow, and oxygen metabolism will be described and their relative advantages and limitations discussed. Several examples of the use of /sup 15/O tracer methods will be reviewed to demonstrate their widespread applicability to the study of cerebral physiology and pathophysiology. 110 references.

  14. Typical cerebral metabolic patterns in neurodegenerative brain diseases.

    PubMed

    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

    2010-10-30

    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 [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

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

    SciTech Connect

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. ); Gillin, J.C. )

    1989-01-01

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

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

    SciTech Connect

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

    1985-05-01

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

  17. Effects of one minimum alveolar anesthetic concentration sevoflurane on cerebral metabolism, blood flow, and CO2 reactivity in cardiac patients.

    PubMed

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

    1999-08-01

    We investigated the cerebral hemodynamic effects of 1 minimum alveolar anesthetic concentration (MAC) sevoflurane anesthesia in nine male patients scheduled for elective coronary bypass grafting. For measurement of cerebral blood flow (CBF), a modified Kety-Schmidt saturation technique was used with argon as an inert tracer gas. Measurements of CBF were performed before the induction of anesthesia and 30 min after induction under normocapnic, hypocapnic, and hypercapnic conditions. Compared with the awake state under normocapnic conditions, sevoflurane reduced the mean cerebral metabolic rate of oxygen by 47% and the mean cerebral metabolic rate of glucose by 39%. Concomitantly, CBF was reduced by 38%, although mean arterial pressure was kept constant. Significant changes in jugular venous oxygen saturation were absent. Hypocapnia and hypercapnia caused a 51% decrease and a 58% increase in CBF, respectively. These changes in CBF caused by variation of Paco2 indicate that cerebrovascular CO2 reactivity persists during 1 MAC sevoflurane anesthesia. We used a modified Kety-Schmidt saturation technique to investigate the effects of 1 minimum alveolar anesthetic concentration (MAC) sevoflurane on cerebral blood flow, metabolism, and CO2 reactivity in cardiac patients. We found that the global cerebral blood flow and global cerebral metabolic rate of oxygen remained coupled and that cerebrovascular CO2 reactivity is not impaired by the administration of 1 MAC sevoflurane.

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

    PubMed

    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

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

    PubMed

    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.

  20. Argon does not affect cerebral circulation or metabolism in male humans

    PubMed Central

    Kazmaier, Stephan; Hoeks, Sanne Elisabeth; Stolker, Robert Jan; Coburn, Marc; Weyland, Andreas

    2017-01-01

    Objective Accumulating data have recently underlined argon´s neuroprotective potential. However, to the best of our knowledge, no data are available on the cerebrovascular effects of argon (Ar) in humans. We hypothesized that argon inhalation does not affect mean blood flow velocity of the middle cerebral artery (Vmca), cerebral flow index (FI), zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe), resistance area product (RAP) and the arterio-jugular venous content differences of oxygen (AJVDO2), glucose (AJVDG), and lactate (AJVDL) in anesthetized patients. Materials and methods In a secondary analysis of an earlier controlled cross-over trial we compared parameters of the cerebral circulation under 15 minutes exposure to 70%Ar/30%O2 versus 70%N2/30%O2 in 29 male patients under fentanyl-midazolam anaesthesia before coronary surgery. Vmca was measured by transcranial Doppler sonography. ZFP and RAP were estimated by linear regression analysis of pressure-flow velocity relationships of the middle cerebral artery. CPPe was calculated as the difference between mean arterial pressure and ZFP. AJVDO2, AJVDG and AJVDL were calculated as the differences in contents between arterial and jugular-venous blood of oxygen, glucose, and lactate. Statistical analysis was done by t-tests and ANOVA. Results Mechanical ventilation with 70% Ar did not cause any significant changes in mean arterial pressure, Vmca, FI, ZFP, CPPe, RAP, AJVDO2, AJVDG, and AJVDL. Discussion Short-term inhalation of 70% Ar does not affect global cerebral circulation or metabolism in male humans under general anaesthesia. PMID:28207907

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

    PubMed Central

    Reitman, Aaron J.; Chapman, Rachel; Stein, James E.; Paquette, Lisa; Panigrahy, Ashok; Nelson, Marvin D.; Friedlich, Philippe

    2016-01-01

    Background Extracorporeal membrane oxygenation (ECMO) is an effective therapy for supporting infants with reversible cardiopulmonary failure. Still, survivors are at risk for long-term neurodevelopmental impairments, the cause of which is not fully understood. Objective To elucidate the effects of ECMO on the newborn brain. We hypothesized that the cerebral metabolic profile of neonates who received ECMO would differ from neonates who did not receive ECMO. To address this, we used magnetic resonance spectroscopy (1H-MRS) to investigate the effects of venoarterial and venovenous ECMO on cerebral metabolism. Methods 41 neonates treated with ECMO were contrasted to 38 age-matched neonates. Results All 1H-MRS data were acquired from standardized grey matter and white matter regions of interest using a short-echo (TE = 35 milliseconds), point-resolved spectroscopy sequence (PRESS) and quantitated using LCModel. Metabolite concentrations (mmol/kg) were compared across groups using multivariate analysis of covariance. Elevated creatine (p = 0.002) and choline (p = 0.005) concentrations were observed in the grey matter among neonates treated with ECMO relative to the reference group. Likewise, choline concentrations were elevated in the white matter (p = 0.003) while glutamate was reduced (p = 0.03). Contrasts between ECMO groups revealed lower osmolite concentrations (e.g. myoinositol) among the venovenous ECMO group. Conclusion Neonates who underwent ECMO were found to have an abnormal cerebral metabolic profile, with the pattern of abnormalities suggestive of an underlying inflammatory process. Additionally, neonates who underwent venovenous ECMO had low cerebral osmolite concentrations as seen in vasogenic edema. PMID:28033354

  2. Changes in cerebral glucose metabolism after an expedition to high altitudes.

    PubMed

    Merz, Tobias M; Treyer, Valerie; Hefti, Urs; Spengler, Christina M; Schwarz, Urs; Buck, Alfred; Maggiorini, Marco

    2006-01-01

    The possibility of persistent cerebral impairment due to exposure to extreme altitude and resulting hypoxic conditions is of great concern to both high altitude mountaineers and researchers. The aim of the present study was to investigate the effect of prolonged exposure to hypoxia on cerebral glucose metabolism, which probably precedes structural and functional impairment. Positron emission tomography (PET) employing [18F]-2-deoxy-2-fluoro-D-glucose (FDG) was performed, and the normobaric hypoxic ventilatory response (HVR) was assessed in 11 mountaineers before (pre) and after (post) climbing Mount Shisha Pangma (8048 m). During the climb, acute mountain sickness (AMS) symptoms were recorded and heart rate and oxygen saturation (SaO2) were measured daily. Neuropsychological evaluations were conducted at different heights. The difference FDGpost- FDGpre was analyzed voxel by voxel using statistical parametric mapping (SPM) and volumes of interest (VOI). SPM revealed two areas of increased cerebral FDG uptake after the expedition, one localized in the left cerebellum (+9.4%) and one in the white matter lateral of the left thalamus (+8.3%). The VOI analysis revealed increased postexpeditional metabolism in an area of the right cerebellum (+11%) and of the thalamus bilaterally (+3.7% on the left, +4.6% on the right). FDG-PET alterations did not correlate with changes in SaO2, HVR, or AMS scores. All neuropsychological test results during the climb were unremarkable. We conclude that a prolonged stay at an extreme altitude leads to regional specific changes in the cerebral glucose metabolism without any signs of neuropsychological impairment during the climb.

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

    PubMed Central

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

    2014-01-01

    Background 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. Methods In neonates monitored with video-EEG, NIRS-measured cerebral regional oxygen saturation (rSO2) and systemic O2 saturation were recorded every 5 seconds. Mean rSO2 was extracted for 1-hour blocks before, during, and after phenobarbital doses. For each electrographic seizure, mean rSO2 was extracted for a period of 3-times the duration of the seizure before and after the ictal pattern, and 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 (FTOE). Results For 20 neonates (EGA 39.6±1.5 weeks), 61 phenobarbital doses and 40 seizures were analyzed. Cerebral rSO2 rose (p=0.005), and FTOE declined (p=0.018) with increasing phenobarbital doses. rSO2 declined during seizures, compared with baseline and post-ictal phases (baseline 81.2 vs. ictal 77.7 vs. post-ictal 79.4; p=0.004). FTOE was highest during seizures (p=0.002). Conclusions 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. PMID:25812123

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

    PubMed

    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.

  5. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex

    PubMed Central

    2010-01-01

    Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project. PMID:18568015

  6. Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: Systematic review and meta-analysis.

    PubMed

    Samarasekera, Neshika; Rodrigues, Mark Alexander; Toh, Pheng Shiew; Salman, Rustam Al-Shahi

    2017-01-01

    We sought to summarize Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) features of intracerebral hemorrhage (ICH) associated with cerebral amyloid angiopathy (CAA) in published observational radio-pathological studies. In November 2016, two authors searched OVID Medline (1946-), Embase (1974-) and relevant bibliographies for studies of imaging features of lobar or cerebellar ICH with pathologically proven CAA ("CAA-associated ICH"). Two authors assessed studies' diagnostic test accuracy methodology and independently extracted data. We identified 22 studies (21 cases series and one cross-sectional study with controls) of CT features in 297 adults, two cross-sectional studies of MRI features in 81 adults and one study which reported both CT and MRI features in 22 adults. Methods of CAA assessment varied, and rating of imaging features was not masked to pathology. The most frequently reported CT features of CAA-associated ICH in 21 case series were: subarachnoid extension (pooled proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies) and an irregular ICH border (64%, 95% CI 32-91%, I2 = 85%, five studies). CAA-associated ICH was more likely to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA-associated ICH 7/41 vs. non-CAA ICH 0/42; χ2 = 7.8, p = 0.005). Superficial siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 = 35%, 3 studies). Subarachnoid extension and an irregular ICH border are common imaging features of CAA-associated ICH, but methodologically rigorous diagnostic test accuracy studies are required to determine the sensitivity and specificity of these features.

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

    SciTech Connect

    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.

  8. Propofol compared with isoflurane inhibits mitochondrial metabolism in immature swine cerebral cortex

    PubMed Central

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

    2014-01-01

    Anesthetics used in infants and children are implicated in the 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 immature swine anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon-labeled glucose and leucine in the common carotid artery 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 with isoflurane, propofol depleted ATP and glycogen stores. Propofol 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 lactate accumulation. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype that resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations that typically accompany propofol infusion syndrome. These metabolic abnormalities may have a role in the neurotoxity observed with propofol in the vulnerable immature brain. PMID:24398942

  9. Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers.

    PubMed

    London, Edythe D; Berman, Steven M; Voytek, Bradley; Simon, Sara L; Mandelkern, Mark A; Monterosso, John; Thompson, Paul M; Brody, Arthur L; Geaga, Jennifer A; Hong, Michael S; Hayashi, Kiralee M; Rawson, Richard A; Ling, Walter

    2005-11-15

    Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

  10. [Differential effects of isoflurane and nitrous oxide on cerebral blood flow, metabolism and electrocorticogram after incomplete cerebral ischemia in the rat].

    PubMed

    Ishikawa, T; Maekawa, T; Shinohara, K; Sakabe, T; Takeshita, H

    1989-07-01

    Differential effects of isoflurane (ISOF) and N2O on cerebral blood flow, metabolism and electrocorticogram (ECoG) were examined in rats subjected to 15 min-incomplete cerebral ischemia. In the first study, regional cerebral blood flow (rCBF) and ECoG were measured during and after ischemia. In the second study, local cerebral blood flow (LCBF) and glucose utilization (LCGU) were determined at 60 min after reperfusion. In the N2O group, rCBF in both the cerebral cortex and hippocampus decreased significantly to less than 10% of the pre-ischemic value during ischemia, and it increased to 170% at 10 min after reperfusion. The ECoG became flat during ischemia and reappeared at 21 min after reperfusion. In the ISOF group, rCBF decreased significantly to 25% during ischemia and returned to the preischemic value after reperfusion. The ECoG became flat during ischemia and reappeared at 14 min. In the N2O group, LCBFs decreased significantly to 40-50% of the pre-ischemic values in the forebrain. LCGUs decreased significantly to 30-50% in all structures of the forebrain. In the ISOF group, LCBFs decreased significantly to 60-80% in the forebrain, but were not different in other structures. LCGUs did not differ from pre-ischemic values in all structures except for in the thalamus and habenula. These results may indicate cerebral protective effects of ISOF on incomplete cerebral ischemia in rats.

  11. Nutrient intake and cerebral metabolism in healthy middle-aged adults: Implications for cognitive aging.

    PubMed

    Oleson, Stephanie; Gonzales, Mitzi M; Tarumi, Takashi; Davis, Jaimie N; Cassill, Carolyn K; Tanaka, Hirofumi; Haley, Andreana P

    2017-10-01

    Growing evidence suggests dietary factors influence cognition, but the effects of nutrient intake on cerebral metabolism in adults are currently unknown. The present study investigated the relationship between major macronutrient intake (fat, carbohydrate, and protein) and cerebral neurochemical profiles in middle-aged adults. Thirty-six adults recorded dietary intake for 3 days prior to completing cognitive testing and a proton magnetic resonance spectroscopy ((1)H-MRS) scan. (1)H-MRS of occipitoparietal gray matter was used to assess glutamate (Glu), N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) relative to creatine (Cr) levels. Regression analyses revealed that high intake of polyunsaturated fatty acids (PUFAs) was associated with lower cerebral Glu/Cr (P = 0.005), and high intake of saturated fat (SFA) was associated with poorer memory function (P = 0.030) independent of age, sex, education, estimated intelligence, total caloric intake, and body mass index. In midlife, greater PUFA intake (ω-3 and ω-6) may be associated with lower cerebral glutamate, potentially indicating more efficient cellular reuptake of glutamate. SFA intake, on the other hand, was linked with poorer memory performance. These results suggest that dietary fat intake modification may be an important intervention target for the prevention of cognitive decline.

  12. Infarctions in the vascular territory of the posterior cerebral artery: clinical features in 232 patients

    PubMed Central

    2011-01-01

    Background Ischemic stroke caused by infarction in the territory of the posterior cerebral artery (PCA) has not been studied as extensively as infarctions in other vascular territories. This single centre, retrospective clinical study was conducted a) to describe salient characteristics of stroke patients with PCA infarction, b) to compare data of these patients with those with ischaemic stroke due to middle cerebral artery (MCA) and anterior cerebral artery (ACA) infarctions, and c) to identify predictors of PCA stroke. Findings A total of 232 patients with PCA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986-2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 232 patients with PCA stroke were compared with those of the 1355 patients with MCA infarctions and 51 patients with ACA infarctions included in the registry. Infarctions of the PCA accounted for 6.8% of all cases of stroke (n = 3808) and 9.6% of cerebral infarctions (n = 2704). Lacunar infarction was the most frequent stroke subtype (34.5%) followed by atherothrombotic infarction (29.3%) and cardioembolic infarction (21.6%). In-hospital mortality was 3.9% (n = 9). Forty-five patients (19.4%) were symptom-free at hospital discharge. Hemianopia (odds ratio [OR] = 6.43), lacunar stroke subtype (OR = 2.18), symptom-free at discharge (OR = 1.92), limb weakness (OR = 0.10), speech disorders (OR = 0.33) and cardioembolism (OR = 0.65) were independent variables of PCA stroke in comparison with MCA infarction, whereas sensory deficit (OR = 2.36), limb weakness (OR = 0.11) and cardioembolism as stroke mechanism (OR = 0.43) were independent variables associated with PCA stroke in comparison with ACA infarction. Conclusions Lacunar stroke is the

  13. Regulation of cerebral cholesterol metabolism in Alzheimer disease.

    PubMed

    Reiss, Allison B; Voloshyna, Iryna

    2012-03-01

    Alzheimer disease (AD) is an age-related neurodegenerative disorder that manifests as a progressive loss of memory and deterioration of higher cognitive functions. Alzheimer disease is characterized by accumulation in the brain of the β-amyloid peptide generated by β- and γ-secretase processing of amyloid precursor protein. Epidemiological studies have linked elevated plasma cholesterol and lipoprotein levels in midlife with AD development. Cholesterol-fed animal models exhibit neuropathologic features of AD including accumulation of β-amyloid peptide. Specific isoforms of the cholesterol transporter apolipoprotein E are associated with susceptibility to AD. Although multiple lines of evidence indicate a role for cholesterol in AD, the exact impact and mechanisms involved remain largely unknown. This review summarizes the current state of our knowledge of the influence of cholesterol and lipid pathways in AD pathogenesis in vitro and in vivo.

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

    PubMed

    Szabo, Z; Camargo, E E; Sostre, S; Shafique, I; Sadzot, B; Links, J M; Dannals, R F; Wagner, H N

    1992-01-01

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

  15. Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism.

    PubMed Central

    Forrester, T; Harper, A M; MacKenzie, E T; Thomson, E M

    1979-01-01

    1. Responses of cerebral blood vessels to peri- and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(-11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(-9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(-7) M and 4 x 10(-6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood-brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow. PMID:119042

  16. Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebral ischemia

    PubMed Central

    2014-01-01

    Neurovascular and gliovascular interactions significantly affect endothelial phenotype. Physiologically, brain endothelium attains several of its properties by its intimate association with neurons and astrocytes. However, during cerebrovascular pathologies such as cerebral ischemia, the uncoupling of neurovascular and gliovascular units can result in several phenotypical changes in brain endothelium. The role of neurovascular and gliovascular uncoupling in modulating brain endothelial properties during cerebral ischemia is not clear. Specifically, the roles of metabolic stresses involved in cerebral ischemia, including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose deprivation and re-oxygenation, OGDR) in modulating neurovascular and gliovascular interactions are not known. The complex intimate interactions in neurovascular and gliovascular units are highly difficult to recapitulate in vitro. However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo. While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential. PMID:24438487

  17. Constancy and trade-offs in the neuroanatomical and metabolic design of the cerebral cortex

    PubMed Central

    Karbowski, Jan

    2014-01-01

    Mammalian brains span about four orders of magnitude in cortical volume and have to operate in different environments that require diverse behavioral skills. Despite these geometric and behavioral diversities, the examination of cerebral cortex across species reveals that it contains a substantial number of conserved characteristics that are associated with neuroanatomy and metabolism, i.e., with neuronal connectivity and function. Some of these cortical constants or invariants have been known for a long time but not sufficiently appreciated, and others were only recently discovered. The focus of this review is to present the cortical invariants and discuss their role in the efficient information processing. Global conservation in neuroanatomy and metabolism, as well as their correlated regional and developmental variability suggest that these two parallel systems are mutually coupled. It is argued that energetic constraint on cortical organization can be strong if cerebral blood supplied is either below or above a certain level, and it is rather soft otherwise. Moreover, because maximization or minimization of parameters associated with cortical connectivity, function and cost often leads to conflicts in design, it is argued that the architecture of the cerebral cortex is a result of structural and functional compromises. PMID:24574975

  18. Constancy and trade-offs in the neuroanatomical and metabolic design of the cerebral cortex.

    PubMed

    Karbowski, Jan

    2014-01-01

    Mammalian brains span about four orders of magnitude in cortical volume and have to operate in different environments that require diverse behavioral skills. Despite these geometric and behavioral diversities, the examination of cerebral cortex across species reveals that it contains a substantial number of conserved characteristics that are associated with neuroanatomy and metabolism, i.e., with neuronal connectivity and function. Some of these cortical constants or invariants have been known for a long time but not sufficiently appreciated, and others were only recently discovered. The focus of this review is to present the cortical invariants and discuss their role in the efficient information processing. Global conservation in neuroanatomy and metabolism, as well as their correlated regional and developmental variability suggest that these two parallel systems are mutually coupled. It is argued that energetic constraint on cortical organization can be strong if cerebral blood supplied is either below or above a certain level, and it is rather soft otherwise. Moreover, because maximization or minimization of parameters associated with cortical connectivity, function and cost often leads to conflicts in design, it is argued that the architecture of the cerebral cortex is a result of structural and functional compromises.

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

    PubMed

    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.

  20. SMART: physical activity and cerebral metabolism in older people: study protocol for a randomised controlled trial.

    PubMed

    Fleckenstein, Johannes; Matura, Silke; Engeroff, Tobias; Füzéki, Eszter; Tesky, Valentina A; Pilatus, Ulrich; Hattingen, Elke; Deichmann, Ralf; Vogt, Lutz; Banzer, Winfried; Pantel, Johannes

    2015-04-11

    Physical activity exerts a variety of long-term health benefits in older adults. In particular, it is assumed to be a protective factor against cognitive decline and dementia. Randomised controlled assessor blinded 2-armed trial (n = 60) to explore the exercise- induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age ≥ 65), recruited within the setting of assisted living facilities and newspaper advertisements are allocated to a 12-week individualised aerobic exercise programme intervention or a 12-week waiting control group. Total follow-up is 24 weeks. The main outcome is the change in cerebral metabolism as assessed with Magnetic Resonance Spectroscopic Imaging reflecting changes of cerebral N-acetyl-aspartate and of markers of neuronal energy reserve. Imaging also measures changes in cortical grey matter volume. Secondary outcomes include a broad range of psychometric (cognition) and movement-related parameters such as nutrition, history of physical activity, history of pain and functional diagnostics. Participants are allocated to either the intervention or control group using a computer-generated randomisation sequence. The exercise physiologist in charge of training opens sealed and opaque envelopes and informs participants about group allocation. For organisational reasons, he schedules the participants for upcoming assessments and exercise in groups of five. All assessors and study personal other than exercise physiologists are blinded. Magnetic Resonance Spectroscopic Imaging gives a deeper insight into mechanisms of exercise-induced changes in brain metabolism. As follow-up lasts for 6 months, this study is able to explore the mid-term cerebral metabolic effects of physical activity assuming that an individually tailored aerobic ergometer training has the potential to counteract brain ageing. NCT02343029 (clinicaltrials.gov; 12 January 2015).

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

    PubMed

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

    2010-03-01

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

  2. Clinical presentation and metabolic features of overt and occult urolithiasis.

    PubMed

    Polito, Cesare; Apicella, Andrea; Marte, Antonio; Signoriello, Giuseppe; La Manna, Angela

    2012-01-01

    Although pediatricians are frequently confronted with patients presenting urolithiasis symptoms without obvious stones, the syndrome of occult urolithiasis may be still viewed with some skepticism. We have compared the clinical and metabolic features of 197 children with obvious calculi, 189 with microcalculi (diameter ≤ 3 mm based on renal sonography), and 114 with symptoms of urolithiasis and normal renal sonography findings. Only microcalculi and normal sonography subjects with a urinary abnormality potentially leading to urolithiasis were included in the study. Age at presentation increased significantly (p = 0.0001) in the groups in the order normal sonography to microcalculi to calculi groups. There was no significant difference among the three groups in terms of family history of urolithiasis, gender distribution, and degree of hypercalciuria, hyperuricosuria, hyperoxaluria, or hypocitraturia. The average frequency of pain attacks of patients with recurrent abdominal pain (RAP) ranged from 3.6 to 4.6 days of pain per month among the three groups, which is four to ninefold lower than that reported for children with functional or organic gastrointestinal RAP. The consistency of many clinical and urinary metabolic characteristics indicates a common underlying disorder in overt and occult urolithiasis. The increase of age at presentation from the normal sonography to microcalculi and calculi groups may reflect progressive crystal accretion leading ultimately to overt stone formation.

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

    PubMed

    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. Ovine middle cerebral artery characterization and quantification of ultrastructure and other features: changes with development.

    PubMed

    Goyal, Ravi; Henderson, David A; Chu, Nina; Longo, Lawrence D

    2012-02-15

    Regulation of tone, blood pressure, and blood flow in the cerebral vasculature is of vital importance, particularly in the developing infant. We tested the hypothesis that, in addition to accretion of smooth muscle cells (SMCs) in cell layers with vessel thickening, significant changes in smooth muscle structure, as well as phenotype, extracellular matrix, and membrane proteins, in the media of cerebral arteries (CAs) during the course of late fetal development account for associated changes in contractility. Using transmission electron, confocal, wide-field epifluorescence, and light microscopy, we examined the structure and ultrastructure of CAs. Also, we utilized wire myography, Western immunoblotting, and real-time quantitative PCR to examine several other features of these arteries. We compared the main branch ovine middle CAs of 95- and 140-gestational day (GD) fetuses with those of adults (n = 5 for each experimental group). We observed a graded increase in phenylephrine- and KCl-induced contractile responses with development. Structurally, lumen diameter, media thickness, and media cross-sectional area increased dramatically from one age group to the next. With maturation, the cross-sectional profiles of CA SMCs changed from flattened bands in the 95-GD fetus to irregular ovoid-shaped fascicles in the 140-GD fetus and adult. We also observed a change in the type of collagen, specific integrin molecules, and several other parameters of SMC morphology with maturation. Ovine CAs at 95 GD appeared morphologically immature and poorly equipped to respond to major hemodynamic adjustments with maturation.

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

    PubMed Central

    Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R; Selmer, Christian; Vogelsang, Thomas; Secher, Niels H

    2004-01-01

    During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O2/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differences (AV) for O2, glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy young subjects. In a second experiment magnetic resonance spectroscopy (1H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AVO2 from 3.2 ± 0.1 at rest to 3.5 ± 0.2 mm (mean ± s.e.m.; P < 0.05) and the AVglc from 0.6 ± 0.0 to 0.9 ± 0.1 mm (P < 0.01). Notably, the AVlac increased from 0.0 ± 0.0 to 1.3 ± 0.2 mm at the point of exhaustion (P < 0.01). Thus, maximal exercise reduced the cerebral metabolic ratio from 6.0 ± 0.3 to 2.8 ± 0.2 (P < 0.05) and it remained low during the early recovery. Despite this, the CSF concentration of lactate postexercise (1.2 ± 0.1 mm; n = 7) was not different from baseline (1.4 ± 0.1 mm; n = 6). Also, the 1H-MRS signal from lactate obtained after exercise was smaller than the estimated detection limit of ∼1.5 mm. The finding that an increase in lactate could not be detected in the CSF or within the brain rules out accumulation in a distribution volume and indicates that the lactate taken up by the brain is metabolized. PMID:14608005

  6. 13C-labelled microdialysis studies of cerebral metabolism in TBI patients☆

    PubMed Central

    Carpenter, Keri L.H.; Jalloh, Ibrahim; Gallagher, Clare N.; Grice, Peter; Howe, Duncan J.; Mason, Andrew; Timofeev, Ivan; Helmy, Adel; Murphy, Michael P.; Menon, David K.; Kirkpatrick, Peter J.; Carpenter, T. Adrian; Sutherland, Garnette R.; Pickard, John D.; Hutchinson, Peter J.

    2014-01-01

    Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons’ tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of 13C-labelled cerebral microdialysis both to deliver 13C-labelled substrates into brains of TBI patients and recover the 13C-labelled metabolites, with high-resolution 13C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of 13C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and 13C research modalities addressing them. PMID:24361470

  7. (13)C-labelled microdialysis studies of cerebral metabolism in TBI patients.

    PubMed

    Carpenter, Keri L H; Jalloh, Ibrahim; Gallagher, Clare N; Grice, Peter; Howe, Duncan J; Mason, Andrew; Timofeev, Ivan; Helmy, Adel; Murphy, Michael P; Menon, David K; Kirkpatrick, Peter J; Carpenter, T Adrian; Sutherland, Garnette R; Pickard, John D; Hutchinson, Peter J

    2014-06-16

    Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons' tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of (13)C-labelled cerebral microdialysis both to deliver (13)C-labelled substrates into brains of TBI patients and recover the (13)C-labelled metabolites, with high-resolution (13)C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of (13)C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and (13)C research modalities addressing them.

  8. Impact of methamphetamine on regional metabolism and cerebral blood flow after traumatic brain injury.

    PubMed

    O'Phelan, Kristine; Ernst, Thomas; Park, Dalnam; Stenger, Andrew; Denny, Katherine; Green, Deborah; Chang, Cherylee; Chang, Linda

    2013-10-01

    Substance abuse is a frequent comorbid condition among patients with traumatic brain injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine (METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use. This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using ImageJ open source software. Pericontusional and contralateral CBF, NAA, and lactate were assessed in the entire cohort and in the METH and non-METH groups. Seventeen subjects completed the MR studies. Analysis of entire cohort: pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12% lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p = 0.03). Lactate concentrations and CBF were not significantly different between the two regions; however, regional CBF was equally reduced in the two regions. Subgroup analysis: 41% of subjects tested positive for METH. The mean age, Glasgow Coma Scale, and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60% lower in the METH users than the non-users, p = 0.04; contralateral CBF did not differ between the groups. This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH

  9. Brain Tissue Oxygenation and Cerebral Metabolic Patterns in Focal and Diffuse Traumatic Brain Injury

    PubMed Central

    Purins, Karlis; Lewén, Anders; Hillered, Lars; Howells, Tim; Enblad, Per

    2014-01-01

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients. Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere). Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level. Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring. PMID:24817863

  10. Anatomic features of distal anterior cerebral artery aneurysms: a detailed angiographic analysis of 101 patients.

    PubMed

    Lehecka, Martin; Porras, Matti; Dashti, Reza; Niemelä, Mika; Hernesniemi, Juha A

    2008-08-01

    Distal anterior cerebral artery (DACA) aneurysms have special anatomic features such as small size, broad base with originating branches, association with anterior cerebral artery (ACA) anomalies, and multiple aneurysms. Our aim is to evaluate incidences of these findings from pretreatment angiograms to help both microsurgical and endovascular treatment planning. We performed detailed angiographic analysis of 101 consecutive patients diagnosed with DACA aneurysms from 1998 to 2007 in the Department of Neurosurgery at the Helsinki University Central Hospital in Helsinki, Finland. All patients underwent either digital subtraction angiography (n = 39) or computed tomographic angiography (n = 62). Of the 101 patients, 50 patients (50%) had multiple aneurysms, 7 patients (7%) had multiple DACA aneurysms, and 1 patient (1%) had an associated arteriovenous malformation. The 108 DACA aneurysms were found in seven different locations: frontobasal branches (n = 2); A2 segment (n = 5); A3 segment inferior to genu of corpus callosum (n = 19), anterior to genu of corpus callosum (n = 70), and superior to genu of corpus callosum (n = 1); A4 or A5 segments (n = 7); and distal branches (n = 4). Mean sizes were 7.4 mm (range, 2-35 mm) and 4.2 mm (range, 1-9 mm) for the 67 ruptured and 41 unruptured aneurysms, respectively. A broad base, wider than the parent artery, was seen in 68% of patients, and 94% of patients had a branch origin at the base. The neck-to-dome ratio was 1:1 in 25% of patients. Anomalies of the ACA were seen in 23 patients (23%): azygos ACA in 4 patients (4%), bihemispheric ACA in 15 patients (15%), and triplication of ACA in 4 patients (4%). The special neurovascular features and frequent ACA anomalies, best identified from computed tomographic angiography or rotational digital subtraction angiography, must be taken into account when planning occlusive treatment of DACA aneurysms.

  11. Sleep Disorders in Parkinson’s Disease: Clinical Features, Iron Metabolism and Related Mechanism

    PubMed Central

    Yu, Shu-yang; Sun, Li; Liu, Zhuo; Huang, Xi-yan; Zuo, Li-jun; Cao, Chen-jie; Zhang, Wei; Wang, Xiao-min

    2013-01-01

    Objective To investigate clinical features, iron metabolism and neuroinflammation in Parkinson’s disease (PD) patients with sleep disorders (SD). Methods 211 PD patients were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a body of scales for motor symptoms and non-motor symptoms. 94 blood and 38 cerebral spinal fluid (CSF) samples were collected and iron and its metabolism-relating proteins, neuroinflammatory factors were detected and analyzed. Results 136 cases (64.5%) of PD patients were accompanied by SD. Factor with the highest score in PSQI was daytime dysfunction. Depression, restless leg syndrome, autonomic symptoms and fatigue contributed 68.6% of the variance of PSQI score. Transferrin level in serum and tumor necrosis factor–α level in CSF decreased, and the levels of iron, transferrin, lactoferrin and prostaglandin E2 in CSF increased in PD patients with SD compared with those without SD. In CSF, prostaglandin E2 level was positively correlated with the levels of transferrin and lactoferrin, and tumor necrosis factor–α level was negatively correlated with the levels of iron, transferrin and lactoferrin in CSF. Conclusions Depression, restless leg syndrome, autonomic disorders and fatigue are the important contributors for the poor sleep in PD patients. Abnormal iron metabolism may cause excessive iron deposition in brain and be related to SD in PD patients through dual potential mechanisms, including neuroinflammation by activating microglia and neurotoxicity by targeting neurons. Hence, inhibition of iron deposition-related neuroinflammation and neurotoxicity may cast a new light for drug development for SD in PD patients. PMID:24376607

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

    SciTech Connect

    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.

  13. Positron emission tomography in ischaemic stroke: cerebral perfusion and metabolism after stroke onset.

    PubMed

    Yasaka, M; Read, S J; O'Keefe, G J; Egan, G F; Pointon, O; McKay, W J; Donnan, G A

    1998-10-01

    PET studies were performed in 37 patients up to 1 month after ischaemic stroke to observe the relationships between cerebral blood flow (CBF), rate of cerebral oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET findings were classified as misery perfusion (two patients), luxury perfusion (15 patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an extended time window during which at least some tissue may be salvageable. Luxury perfusion, an indication of non-nutritional flow, was seen as early as 30 h and as late as 23 days, but more commonly between 3 and 7 days. A matched reduction of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours. Since this was associated with severely impaired CBF, presumably from the onset of stroke, it can be assumed that the duration of cerebral tissue survival is less than 27 h under these conditions. We inferred that, for maximal tissue recovery, therapy will need to be introduced within 27 h after stroke, but that at least some potential for recovery exists up to 3 days.

  14. Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

    PubMed Central

    Brooks, Steven D.; DeVallance, Evan; d'Audiffret, Alexandre C.; Tabone, Lawrence E.; Shrader, Carl D.; Frisbee, Jefferson C.; Chantler, Paul D.

    2015-01-01

    The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7–8, 12–13, and 16–17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7–8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. PMID:26475592

  15. Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic–Ischemic Brain Injury

    PubMed Central

    Mitra, Subhabrata; Bale, Gemma; Mathieson, Sean; Uria-Avellanal, Cristina; Meek, Judith; Tachtsidis, Ilias; Robertson, Nicola J.

    2016-01-01

    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 electroencephalogram. 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 electroencephalogram 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. PMID:27559538

  16. Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats.

    PubMed

    Brooks, Steven D; DeVallance, Evan; d'Audiffret, Alexandre C; Frisbee, Stephanie J; Tabone, Lawrence E; Shrader, Carl D; Frisbee, Jefferson C; Chantler, Paul D

    2015-12-01

    The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    Venkat, Poornima; Chopp, Michael; Chen, Jieli

    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. 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. PMID:27374823

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

    PubMed

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

    2013-09-01

    Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism. Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging. CBF was measured using pseudo-continuous arterial spin labeling. N-acetylaspartate/creatine (NAA/Cr) ratios (axonal mitochondrial metabolism) were obtained using (1)H-MR spectroscopy and PCr/β-ATP ratios using (31)P-MR spectroscopy. In centrum semiovale NAWM, we assessed correlations between CBF and both NAA/Cr and PCr/β-ATP ratios. Subjects with MS had a widespread reduction in CBF of NAWM (centrum semiovale, periventricular, frontal and occipital), and gray matter (frontoparietal cortex and thalamus). Compared to controls, NAA/Cr in NAWM of the centrum semiovale of MS subjects was decreased, whereas PCr/β-ATP was increased. We found no correlations between CBF and PCr/β-ATP. CBF and NAA/Cr correlated in controls (p = 0.02), but not in MS subjects (p = 0.68). Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

  1. Sequential metabolic changes in rat brain following middle cerebral artery occlusion: A 2-deoxyglucose study

    SciTech Connect

    Shiraishi, K.; Sharp, F.R.; Simon, R.P. )

    1989-12-01

    The distribution and time course of altered cerebral metabolism following permanent focal ischemia was studied in rat using the 2-deoxyglucose (2DG) technique. Increased 2DG uptake preceded decreased 2DG uptake and infarction in the caudate putamen and cortex. Decreased 2DG uptake without infarction was observed for 72 h in thalamus and for 24 h in hippocampus (areas remote from the ischemic zones). This study supports the concept of cell excitation as a pathophysiologic process in permanent focal ischemia. The time course of increased metabolism may demarcate the time window of opportunity for the previously demonstrated attenuation of stroke size with inhibition of cell excitation by pharmacologic blockade of excitatory amino acid neurotransmission.

  2. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    PubMed

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

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

    PubMed

    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 < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated 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.

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

    PubMed Central

    Harrell, John W.

    2013-01-01

    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 < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated 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. PMID:24213610

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    SciTech Connect

    Hingorani, V.; Brecher, P.

    1987-05-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

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

    SciTech Connect

    Clow, D.W.; Hammer, R.P. Jr. )

    1991-01-01

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

  8. Increase of reactive oxygen species generation in cerebral cortex slices after the transiently enhanced metabolic activity.

    PubMed

    Sasaki, Toru; Awaji, Takuji; Shimada, Kazuyoshi; Sasaki, Haruyo

    2017-10-01

    Under certain conditions such as hypoxia-reoxygenation, the generation of reactive oxygen species (ROS) increases following hypoxia caused by a decreased oxygen supply. As another hypoxic condition, an excess neural activity status including epileptic seizure induces a decrease in tissue oxygen partial pressure (pO2) caused by enhanced oxygen utilization; however, whether ROS generation increases following the hypoxic status induced by transiently enhanced energy metabolism in brain tissue currently remains unknown. We herein investigated ROS-dependent chemiluminescence in cerebral cortex slices during the restoration of transiently enhanced energy metabolism induced by a high-potassium treatment with tissue pO2 changes and redox balance. ROS generation in the tissue was enhanced after high-potassium-induced hypoxia, but not by the reversed order of the treatment: control-potassium then high-potassium treatment, high-potassium treatment alone, and control-potassium treatment alone. The high-potassium treatment induced a transient decrease in tissue pO2 and a shift in the tissue redox balance towards reduction. The transient shift in the tissue redox balance towards reduction with enhanced metabolic activity and its recovery may correlate with ROS generation. This phenomenon may mimic ROS generation following the hypoxic status induced by transiently enhanced energy metabolism. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  9. Cerebral acetylcholine and energy metabolism changes in acute ammonia intoxication in the lower primate Tupaia glis.

    PubMed

    McCandless, D W; Looney, G A; Modak, A T; Stavinoha, W B

    1985-08-01

    Ammonia levels are elevated in many patients with hepatic encephalopathy. This observation, coupled with animal studies showing an encephalogenic role for ammonia, has led to the concept that ammonia is an important toxin in the production of neurologic symptoms. Studies in rodents have shown that ammonia alters cerebral energy metabolism in the reticular formation, an area important in the modulation of consciousness. Our study was undertaken to extend these observations to the lower primate Tupaia glis, the tree shrew. The energy metabolites glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine were measured in the reticular formation by microanalytic techniques and enzymatic cycling. Acetylcholine was measured in brain regions by gas chromatography. Acetylcholine levels were increased significantly only in the medulla-pons and diencephalon in the coma stage. The energy metabolites glucose, glycogen, and phosphocreatine were decreased in reticular formation cells during the coma, whereas lactate was increased. During the precoma, glycogen and phosphocreatine were decreased. It appears, therefore, that the tree shrew has a metabolic response to ammonia similar to that of mice. A lowering of energy metabolism in the area of brain-regulating consciousness may act to place the animal in a coma. This coma in turn acts to decrease overall metabolic demand, which allows the animal an opportunity to conserve its threatened energy reserves.

  10. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    SciTech Connect

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-06-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.

  11. [Effect of needling at waiguan (SJ5) on brain glucose metabolism in patients with cerebral infarction].

    PubMed

    Liu, En-Tao; Wang, Shu-Xia; Huang, Yong; Lai, Xin-Sheng; Tang, Chun-Zhi; Cui, Shao-Yang

    2013-10-01

    To observe changes of brain glucose metabolism by needling at Waiguan (SJ5) in cerebral infraction (CI) patients using 18F-fluorodeoxyglucose (FDG) positron-emission computer tomography (PET/CT), thus exploring its effect and mechanisms. A total of 21 patients with CI were recruited in this study. The location of lesion was limited to the left basal ganglia by CT or MRI scan. All patients were randomly assigned to three groups. i.e., the acupoint group (Group A), the non-acupoint group (Group B), the blank control group (Group C), 7 in each group. Patients in Group A were needled at right Waiguan (SJ5). Those in Group B were needled at non-acupoint [10 mm beside Waiguan (SJ5)], whereas those in Group C did not receive any treatment. All patients underwent PET/CT head scan. All data were statistically analyzed using SPSS 13.0 Software and SPM8 Software. Compared with Group C, glucose metabolism increased in bilateral superior temporal gyrus (BA38), right superior frontal gyrus (BA9), left cingulate gyrus (BA24), left culmen and pyramid of cerebellum, and right cerebellar tonsil of cerebellum in Group A. Compared with Group C, glucose metabolism increased in bilateral superior frontal gyrus (BA6, BA9, BA10), bilateral middle frontal gyrus (BA6, BA10), left middle frontal gyrus (BA4), bilateral uncus of limbic lobe (BA36, BA38), left cingulate gyrus (BA24, BA31), left posterior cingulate gyrus (BA30), left precuneus (BA7), left inferior parietal lobule (BA4), and left lingual gyrus of occipital lobe (BA18) in Group B. Compared with Group B, glucose metabolism increased in bilateral superior temporal gyrus (BA22, BA38), right inferior frontal gyrus (BA47), left culmen and cerebellar tonsil of cerebellum in Group A. Activated encephalic regions of needling at Waiguan (SJ5) were mainly dominated in the healthy side, bilateral superior temporal gyrus, and right inferior frontal gyrus. Activated encephalic regions of cerebellum were located at the left cerebellar

  12. Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

    PubMed

    Berman, S M; Voytek, B; Mandelkern, M A; Hassid, B D; Isaacson, A; Monterosso, J; Miotto, K; Ling, W; London, E D

    2008-09-01

    Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

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

    PubMed

    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 < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout 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, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 .

  14. Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.

    PubMed

    Popp, Julius; Meichsner, Sabrina; Kölsch, Heike; Lewczuk, Piotr; Maier, Wolfgang; Kornhuber, Johannes; Jessen, Frank; Lütjohann, Dieter

    2013-07-01

    The disturbances of the cholesterol synthesis and metabolism described in Alzheimer's disease (AD) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis. These putative relationships and their underlying mechanisms are not well understood. The aim of this study was to evaluate the relationship between the cerebral and extracerebral cholesterol synthesis and metabolism, and the AD pathology as reflected by CSF markers in humans. We evaluated the relationships between the plasma and the cerebrospinal fluid (CSF) concentrations of cholesterol, the cholesterol precursors lanosterol, lathosterol and desmosterol, and the cholesterol elimination products 24S-hydroxycholesterol and 27-hydroxycholesterol, and the CSF markers for AD pathology Aβ1-42 and p-tau181 in 86 subjects with normal cognition and in 107 AD patients. CSF desmosterol, cholesterol and 24S-hydroxycholesterol in the AD group, and CSF 24S-hydroxycholesterol in the control group correlated with the p-tau181 levels. Neither CSF nor plasma concentrations of the included compounds correlated with the CSF Aβ1-42 levels. In multivariate regression tests including age, gender, albumin ratio, number of the APOEε4 alleles, and diagnosis, p-tau181 levels independently predicted the CSF desmosterol, cholesterol and 24S-hydroxycholesterol concentrations. The associations remained significant for CSF cholesterol and 24S-hydroxycholesterol when analyses were separately performed in the AD group. The results suggest that alterations of CNS cholesterol de novo genesis and metabolism are related to neurodegeneration and in particular to the cerebral accumulation of phosphorylated tau.

  15. Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic–Ischemic Fetal Lambs during Postnatal Life

    PubMed Central

    Rey-Santano, Carmen; Mielgo, Victoria E.; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-del-Yerro, Estibaliz; Valls-i-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J.

    2011-01-01

    The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic–ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury. PMID:21960958

  16. Cerebral blood flow and metabolism during cardiopulmonary bypass with special reference to effects of hypotension induced by prostacyclin

    SciTech Connect

    Feddersen, K.; Aren, C.; Nilsson, N.J.; Radegran, K.

    1986-04-01

    Cerebral blood flow and metabolism of oxygen, glucose, and lactate were studied in 43 patients undergoing aortocoronary bypass. Twenty-five patients received prostacyclin infusion, 50 ng per kilogram of body weight per minute, during cardiopulmonary bypass (CPB), and 18 patients served as a control group. Regional cerebral blood flow (CBF) was studied by intraarterially injected xenon 133 and a single scintillation detector. Oxygen tension, carbon dioxide tension, oxygen saturation, glucose, and lactate were measured in arterial and cerebral venous blood. Mean arterial blood pressure decreased during hypothermia and prostacyclin infusion to less than 30 mm Hg. The regional CBF was, on average, 22 (standard deviation (SD) 4) ml/100 gm/min before CPB. It increased in the control group during hypothermia to 34 (SD 12) ml/100 gm/min, but decreased in the prostacyclin group to 15 (SD 5) ml/100 gm/min. It increased during rewarming in the prostacyclin group. After CPB, regional CBF was about 40 ml/100 gm/min in both groups. The cerebral arteriovenous oxygen pressure difference decreased more in the control group than in the prostacyclin group during hypothermia. The cerebral metabolic rate of oxygen decreased in both groups from approximately 2 ml/100 gm/min to about 1 ml/100 gm/min during hypothermia, increased again during rewarming, and after CPB was at the levels measured before bypass in both groups. There was no difference between the groups in regard to glucose and lactate metabolism.

  17. Effects of selective head cooling on cerebral blood flow and metabolism in newborn piglets after hypoxia-ischemia.

    PubMed

    Cheng, Guoqiang; Sun, Jinqiao; Wang, Laishuan; Shao, Xiaomei; Zhou, Wenhao

    2011-02-01

    the effect of selective head cooling on cerebral blood flow (CBF) and cerebral metabolism rate (CMR) was investigated in newborn piglets. seven days old newborn piglets were randomly assigned to one of the following three groups: Selective head cooling in normal piglets (n=4), selective head cooling after HI (n=6) and normal temperature after HI (n=6). CBF was measured with color microspheres. Cerebral oxygenation metabolism rate (CMRO(2)), Cerebral glucose consumption (CMR(Glu)) and Cerebral lactate production (CMR(lac)) were calculated. in normal piglets, CBF, CMRO(2) and CMR(glu) were significantly decreased at both 35°C (P<0.05) and 32°C (P<0.01), while CMR(lac) did not change. Compared to baseline, CBF and CMRO(2) were significantly reduced (P<0.05), while CMR(glu) and CMR(lac) were significantly increased (P<0.01), AVDO(2) was decreased (P<0.05), while AVD(glu) and AVD(lac) were significantly increased (P<0.01 respectively) in HI piglets with normal temperature respectively. Compared to normal temperature after HI, selective head cooling after HI significantly reduced CMR(glu) and CMR(lac), and AVDO(2), AVD(glu), AVD(lac) were improved at 35°C. selective head cooling not only reduced energy consumption, but also improve brain oxygen metabolism in newborn after HI. 2010 Elsevier Ltd. All rights reserved.

  18. [Features of the periodontal pathology at patients with metabolic syndrome].

    PubMed

    Ermolaeva, L A; Shishkin, A N; Sheveleva, N A; Penkovoi, E A; Sheveleva, M A; Sokolovich, N A; Khabarova, O V; Mihailova, E S

    2016-01-01

    The purpose of this article is to familiarize readers on the relationship between metabolic syndrome and periodontitis, as well as common pathogenetic processes underlying these diseases. The data of modern researches, devoted to the correlation of lesions of periodontal and systemic diseases associated with metabolic syndrome. In the article analyzed also the data of the original study of the interaction of periodontitis and metabolic syndrome, which also used special methods of examination like Doppler ultrasound microcirculatory vasculature of the periodontal tissues and ultrasound densitometry. The possible methods of diagnostics of a condition of periodontal tissues in patients with metabolic syndrome are considered. Conclusions about the relationship of each component of metabolic syndrome with periodontitis are made.

  19. Cerebral energy metabolism in diving and non-diving birds during hypoxia and apnoeic asphyxia.

    PubMed Central

    Bryan, R M; Jones, D R

    1980-01-01

    1. Cerebral energy metabolism during apnoeic asphyxia and steady-state hypoxia was compared in ducks and chickens; ducks tolerate apnoeic asphyxia 3-8 times longer than chickens. 2. Fluctuations in the reduced form of respiratory chain nicotinamide adenine dinucleotide (NADH) were monitored from the left cerebral hemisphere by a noninvasive fluorometric technique and used as an indicator of mitochondrial hypoxia. NADH fluorescence was expressed in aribtrary units (a.u.) where 100 a.u. was defined as the fluorescence change from normoxia to anoxia. Electroencephalogram (e.e.g.) and surface Po2 were recorded from the right hemisphere. 3. After 1 min of asphyxia NADH fluorescence increased by 37 a.u.+/-3.60 S.E. of mean (n=54) in paralysed chickens and 8 a.u.+/-1.41 (n=55) in aralysed ducks. After 2 min the fluorescence increased by only 15 a.u.+/-1.95 in ducks. 4. Both species showed an isoelectric e.e.g. when fluorescence increased by approximately 35 a.u., indicating that anaerobic ATP production in ducks did not maintain brain function (e.e.g.) for a greater accumulation of respiratory chain NADH. 5. At a given decrease in tissue Po2 ducks and chickens showed the same level of NADH increase, indicating that both species are equally dependent on tissue Po2 for the maintenance of redox state. 6. We conclude that biochemical adjustment which enhance anaerobic ATP production and/or prolong oxidative phosphorylation during progressive hypoxia are not responsible for increased cerebral tolerance to apnoeic asphyxia in the duck. PMID:7381772

  20. Early postoperative changes in cerebral oxygen metabolism following neonatal cardiac surgery: Effects of surgical duration

    PubMed Central

    Buckley, Erin M.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Baker, Wesley B.; Durduran, Turgut; Busch, David R.; Nicolson, Susan C.; Montenegro, Lisa M.; Naim, Maryam Y.; Xiao, Rui; Spray, Thomas L.; Yodh, A. G.; Gaynor, J. William; Licht, Daniel J.

    2013-01-01

    Objective The early postoperative period following neonatal cardiac surgery is a time of increased risk for brain injury, yet the mechanisms underlying this risk are unknown. To understand these risks more completely, we quantified changes in postoperative cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood flow (CBF) compared with preoperative levels by using noninvasive optical modalities. Methods Diffuse optical spectroscopy and diffuse correlation spectroscopy were used concurrently to derive cerebral blood flow and oxygen utilization postoperatively for 12 hours. Relative changes in CMRO2, OEF, and CBF were quantified with reference to preoperative data. A mixed-effect model was used to investigate the influence of total support time and deep hypothermic circulatory arrest duration on relative changes in CMRO2, OEF, and CBF. Results Relative changes in CMRO2, OEF, and CBF were assessed in 36 patients, 21 with single-ventricle defects and 15 with 2-ventricle defects. Among patients with single-ventricle lesions, deep hypothermic circulatory arrest duration did not affect relative changes in CMRO2, CBF, or OEF (P > .05). Among 2-ventricle patients, total support time was not a significant predictor of relative changes in CMRO2 or CBF (P > .05), although longer total support time was associated significantly with greater increases in relative change of postoperative OEF (P = .008). Conclusions Noninvasive diffuse optical techniques were used to quantify postoperative relative changes in CMRO2, CBF, and OEF for the first time in this observational pilot study. Pilot data suggest that surgical duration does not account for observed variability in the relative change in CMRO2, and that more comprehensive clinical studies using the new technology are feasible and warranted to elucidate these issues further. PMID:23111021

  1. Safety of lumbar puncture in comatose children with clinical features of cerebral malaria.

    PubMed

    Moxon, Christopher A; Zhao, Lei; Li, Chenxi; Seydel, Karl B; MacCormick, Ian J; Diggle, Peter J; Mallewa, Macpherson; Solomon, Tom; Beare, Nicholas A; Glover, Simon J; Harding, Simon P; Lewallen, Susan; Kampondeni, Sam; Potchen, Michael J; Taylor, Terrie E; Postels, Douglas G

    2016-11-29

    We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM). This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness. Propensity score-based analyses were used to adjust for this bias and assess the independent association between LP and mortality. Data were available for 1,075 children: 866 (80.6%) underwent LP and 209 (19.4%) did not. Unadjusted mortality rates were lower in children who underwent LP (15.3% vs 26.7% in the no-LP group) but differences in covariates between the 2 groups suggested bias in LP allocation. After propensity score matching, all covariates were balanced. Propensity score-based analyses showed no change in mortality rate associated with LP: by inverse probability weighting, the average risk reduction was 2.0% at 12 hours (95% confidence interval -1.5% to 5.5%, p = 0.27) and 1.7% during hospital admission (95% confidence interval -4.5% to 7.9%, p = 0.60). Undergoing LP did not change the risk of mortality in subanalyses of children with severe brain swelling on MRI or in those with papilledema. In comatose children with suspected CM who were clinically stable, we found no evidence that LP increases mortality, even in children with objective signs of raised intracranial pressure. © 2016 American Academy of Neurology.

  2. Safety of lumbar puncture in comatose children with clinical features of cerebral malaria

    PubMed Central

    Moxon, Christopher A.; Zhao, Lei; Li, Chenxi; Seydel, Karl B.; MacCormick, Ian J.; Diggle, Peter J.; Mallewa, Macpherson; Solomon, Tom; Beare, Nicholas A.; Glover, Simon J.; Harding, Simon P.; Lewallen, Susan; Kampondeni, Sam; Potchen, Michael J.; Taylor, Terrie E.

    2016-01-01

    Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM). Methods: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness. Propensity score–based analyses were used to adjust for this bias and assess the independent association between LP and mortality. Results: Data were available for 1,075 children: 866 (80.6%) underwent LP and 209 (19.4%) did not. Unadjusted mortality rates were lower in children who underwent LP (15.3% vs 26.7% in the no-LP group) but differences in covariates between the 2 groups suggested bias in LP allocation. After propensity score matching, all covariates were balanced. Propensity score–based analyses showed no change in mortality rate associated with LP: by inverse probability weighting, the average risk reduction was 2.0% at 12 hours (95% confidence interval −1.5% to 5.5%, p = 0.27) and 1.7% during hospital admission (95% confidence interval −4.5% to 7.9%, p = 0.60). Undergoing LP did not change the risk of mortality in subanalyses of children with severe brain swelling on MRI or in those with papilledema. Conclusion: In comatose children with suspected CM who were clinically stable, we found no evidence that LP increases mortality, even in children with objective signs of raised intracranial pressure. PMID:27794112

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

    PubMed Central

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

    2003-01-01

    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

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

    PubMed

    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. Gender difference in relationship between anxiety-related personality traits and cerebral brain glucose metabolism.

    PubMed

    Hakamata, Yuko; Iwase, Mikio; Iwata, Hiroshi; Kobayashi, Toshiki; Tamaki, Tsuneo; Nishio, Masami; Matsuda, Hiroshi; Ozaki, Norio; Inada, Toshiya

    2009-09-30

    Recent functional neuroimaging studies have suggested that specific brain regions might be associated with the formation of anxiety-related personality traits, which are well known to be influenced by gender. Such anxiety-related personality traits are one of the representative predisposing factors for mood and anxiety disorders, whose incidence is also known to be much influenced by gender. However, little is known about the gender differences in brain function related to anxiety-related personality traits. The aim of the present study was to examine gender-related differences in the pattern of the relationships between an anxiety-related personality trait and cerebral brain glucose metabolism. Regional brain glucose metabolism was measured using [(18)F]fluorodeoxyglucose positron emission tomography in 102 healthy subjects (65 males and 37 females). An anxiety-related trait was assessed using the Temperament and Character Inventory dimension Harm Avoidance (HA). HA was negatively correlated with glucose metabolism in the anterior portion of the ventromedial prefrontal cortex (vmPFC) in females but not in males. The anterior vmPFC may be a possible neural target for the prevention or therapy of emotional disorders, especially in females.

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

    PubMed

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

    2014-07-01

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

  7. Metabolic, cardiorespiratory, and neuromuscular fitness performance in children with cerebral palsy: A comparison with healthy youth

    PubMed Central

    García, Claudia Cardona; Alcocer-Gamboa, Alberto; Ruiz, Margarita Pérez; Caballero, Ignacio Martínez; Faigenbaum, Avery D.; Esteve-Lanao, Jonathan; Saiz, Beatriz Moral; Lorenzo, Teresa Martín; Lara, Sergio Lerma

    2016-01-01

    The aim of this study was to assess metabolic, cardiorespiratory, and neuromuscular fitness parameters in children with spastic cerebral palsy (CP) and to compare these findings with typically developing children. 40 children with CP (21 males, 19 females; mean age, 11.0±3.3 yr; range, 6.5–17.1 yr; Gross Motor Function Classification System levels 1 or 2) and 40 healthy, age- and sex-matched children completed a test battery that consisted of 8 tests and 28 measures that assessed cardio-respiratory fitness, energy expenditure, anaerobic endurance, muscle strength, agility, stability and flexibility. Children with CP had significantly lower performance (P<0.05) on most cardiorespiratory and metabolic tests than those of healthy children, Differences in neuromuscular measures of muscular strength, speed, agility, anaerobic endurance, and flexibility between groups were most apparent. Grouped differences in cardiorespiratory variables revealed a 25% difference in performance, whereas grouped differences in metabolic and neuromuscular measures were 43% and 60%, respectively. The physical fitness of contemporary children with CP is significantly less than healthy, age-matched children. Significant differences in neuromuscular measures between groups can aid in the identification of specific fitness abilities in need of improvement in this population. PMID:27162775

  8. Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

    SciTech Connect

    Davis, D.W.

    1987-01-01

    Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of (6-/sup 14/C) glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg/sup -1/) and anesthetic (30 mg kg /sup -1/) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations.

  9. Cerebral Metabolic Differences Associated with Cognitive Impairment in Parkinson’s Disease

    PubMed Central

    Liu, Fengtao; Wu, Ping; Guo, Sisi; Liu, Zhenyang; Wang, Yixuan; Wang, Ying; Ding, Zhengtong; Wu, Jianjun; Zuo, Chuantao; Wang, Jian

    2016-01-01

    Purpose To characterize cerebral glucose metabolism associated with different cognitive states in Parkinson’s disease (PD) using 18F-fluorodeoxyglucose (FDG) and Positron Emission Tomography (PET). Methods Three groups of patients were recruited in this study including PD patients with dementia (PDD; n = 10), with mild cognitive impairment (PD-MCI; n = 20), and with no cognitive impairment (PD-NC; n = 30). The groups were matched for age, sex, education, disease duration, motor disability, levodopa equivalent dose and Geriatric Depression Rating Scale (GDS) score. All subjects underwent a FDG-PET study. Maps of regional metabolism in the three groups were compared using statistical parametric mapping (SPM5). Results PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and parahippocampal gyrus compared with the PD-NC patients (p < 0.01). PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01), and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01). Conclusions Compared with PD-NC patients, hypometabolism was much higher in the PDD patients than in PD-MCI patients, mainly in the posterior cortical areas. The result might suggest an association between posterior cortical hypometabolism and more severe cognitive impairment. PD-MCI might be important for early targeted therapeutic intervention and disease modification. PMID:27064684

  10. Caffeine’s effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism

    PubMed Central

    Chen, Yufen; Parrish, Todd B.

    2009-01-01

    The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO2) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO2. The present study used the calibrated BOLD approach with 5% CO2 to determine if a 2.5mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO2 during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO2 coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO2. These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine. PMID:19000770

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

    PubMed

    Hansen, M B; Olsen, N V; Hyldegaard, O

    2013-11-01

    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 scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

  12. Improving estimates of the cerebral metabolic rate of oxygen from optical imaging data.

    PubMed

    Barrett, Matthew J P; Suresh, Vinod

    2015-02-01

    The cerebral metabolic rate of oxygen (CMRO2) is an important measure of brain function. Since it is challenging to measure directly, especially dynamically, a number of neuroimaging techniques aim to infer activation-induced changes in CMRO2 from indirect data. Here, we employed a mathematical modelling approach, based on fundamental biophysical principles, to investigate the validity of the widely-used method to calculate CMRO2 from optical measurements of cerebral blood flow and haemoglobin saturation. In model-only simulations and simulations of in vivo data changes in CMRO2 calculated in this way differed substantially from the changes in CMRO2 directly imposed on the model, under both steady state and dynamic conditions. These results suggest that the assumptions underlying the calculation method are not appropriate, and that it is important to take into account, under steady state conditions: 1) the presence of deoxyhaemoglobin in arteriolar vessels; and 2) blood volume changes, especially in veins. Under dynamic conditions, the model predicted that calculated changes in CMRO2 are moderately correlated with the rate of oxygen extraction--not consumption--during the initial phase of stimulation. However, during later phases of stimulation the calculation is dominated by the change in blood flow. Therefore, we propose that a more sophisticated approach is required to estimate CMRO2 changes from these types of data.

  13. Dehydroepiandrosterone (DHEA) treatment stimulates oxidative energy metabolism in the cerebral mitochondria from developing rats.

    PubMed

    Patel, Minal A; Katyare, Surendra S

    2006-08-01

    Effects of treatment with dehydroepiandrosterone (DHEA) (0.2 or 1.0mg/kg body weight for 7 days) on oxidative energy metabolism in cerebral mitochondria from developing and young adult rats were examined. Treatment with DHEA did not change the body weight of developing rats but resulted in increase in the brain weight in 5 week group. In young adult rats the body weight increased following treatment with 1.0mg DHEA. State 3 and state 4 respiration rates with all the substrates increased following DHEA treatment, the effect being more pronounced in the developing rats. State 4 respiration rates were stimulated to variable extents. Contents of cytochromes aa(3) and b increased following DHEA treatment and once again the effect was more pronounced in the developing rats. DHEA treatment marginally changed the content of cytochromes c+c(1). In the developing rats the ATPase activity and the levels of dehydrogenases increased significantly by DHEA treatment. Results of our studies have shown that treatment with exogenous DHEA accelerates the process of maturation of cerebral mitochondria thus emphasizing the role of DHEA in brain development in postnatal life.

  14. Cerebral metabolic effects of fluoxetine, fluvoxamine, paroxetine and sertraline in the conscious rat.

    PubMed

    Freo, Ulderico; Merico, Antonio; Ermani, Mario; Ori, Carlo

    2008-05-09

    The selective serotonin reuptake inhibitors (SSRI) exert a wide range of neurochemical and therapeutic activities. To investigate the neural effectors of SSRIs, we measured the regional cerebral metabolic rates for glucose (rCMRglc) in 56 brain regions of Fischer-344 rats 30 min after intraperitoneal injection of 0.4, 4 or 40 mg/kg of fluoxetine or fluvoxamine or after 4 mg/kg of paroxetine or sertraline. Both shared and drug-specific effects were detected. While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula. The topography and the relation to dose of rCMRglc reductions by SSRIs differ from those of other classes of antidepressants, thus suggesting that SSRIs may specifically modulate brain areas involved in the physiological responses to stress.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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.

    2010-01-01

    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. PMID:20615033

  17. Effect of metabolic syndrome on pathologic features of prostate cancer.

    PubMed

    Kheterpal, Emil; Sammon, Jesse D; Diaz, Mireya; Bhandari, Akshay; Trinh, Quoc-Dien; Pokala, Naveen; Sharma, Pranav; Menon, Mani; Agarwal, Piyush K

    2013-10-01

    The prevalence of metabolic syndrome has been increasing worldwide, however its association with prostate cancer (CaP) is unclear. We reviewed patients undergoing robot assisted radical prostatectomy (RARP) to evaluate if those with metabolic syndrome had more aggressive disease. A prospective database of patients undergoing RARP between January 2005 and December 2008 (n = 2756) was queried for components of metabolic syndrome (BMI ≥ 30 and ≥ 2 of the following: hypertension, diabetes or elevated blood glucose, and dyslipidemia; n = 357). Patients with no components of metabolic syndrome were used as controls (n = 694). Biopsy and final pathology were compared between the 2 groups using all controls, and using best-matched controls (n = 357) based on greedy matching by propensity score. Compared with unmatched controls, metabolic syndrome patients had higher pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and higher pathologic stage (≥ T3 disease: 43% vs. 31%, P < 0.001). After controlling for confounders, those with metabolic syndrome when compared with best-matched controls had maintained the greater pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and pathologic stage (≥ T3 disease: 43% vs. 32%, P < 0.001). They also had significantly greater pathologic upgrading of Gleason grade 6 adenocarcinoma found on biopsy compared with best-matched controls (63% vs. 45%, P < 0.001). On pathology, a 2-fold increase in Gleason 8 and greater was noted between patients with metabolic syndrome and best-matched controls (15% vs. 8%). After controlling for confounders, patients with metabolic syndrome were found to have higher Gleason grade and tumor stage on final pathology and were more likely to have upgrading. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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.

  19. A primitive study of voxel feature generation by multiple stacked denoising autoencoders for detecting cerebral aneurysms on MRA

    NASA Astrophysics Data System (ADS)

    Nemoto, Mitsutaka; Hayashi, Naoto; Hanaoka, Shouhei; Nomura, Yukihiro; Miki, Soichiro; Yoshikawa, Takeharu; Ohtomo, Kuni

    2016-03-01

    The purpose of this study is to evaluate the feasibility of a novel feature generation, which is based on multiple deep neural networks (DNNs) with boosting, for computer-assisted detection (CADe). It is hard and time-consuming to optimize the hyperparameters for DNNs such as stacked denoising autoencoder (SdA). The proposed method allows using SdA based features without the burden of the hyperparameter setting. The proposed method was evaluated by an application for detecting cerebral aneurysms on magnetic resonance angiogram (MRA). A baseline CADe process included four components; scaling, candidate area limitation, candidate detection, and candidate classification. Proposed feature generation method was applied to extract the optimal features for candidate classification. Proposed method only required setting range of the hyperparameters for SdA. The optimal feature set was selected from a large quantity of SdA based features by multiple SdAs, each of which was trained using different hyperparameter set. The feature selection was operated through ada-boost ensemble learning method. Training of the baseline CADe process and proposed feature generation were operated with 200 MRA cases, and the evaluation was performed with 100 MRA cases. Proposed method successfully provided SdA based features just setting the range of some hyperparameters for SdA. The CADe process by using both previous voxel features and SdA based features had the best performance with 0.838 of an area under ROC curve and 0.312 of ANODE score. The results showed that proposed method was effective in the application for detecting cerebral aneurysms on MRA.

  20. Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo.

    PubMed

    Du, Congwu; Pan, Yingtian

    2011-01-01

    It is known that a remaining challenge for functional brain imaging is to distinguish the coupling and decoupling effects among neuronal activity, cerebral metabolism, and vascular hemodynamics, which highlights the need for new tools to enable simultaneous measures of these three properties in vivo. Here, we review current neuroimaging techniques and their prospects and potential limitations for tackling this challenge. We then report a novel dual-wavelength laser speckle imaging (DW-LSI) tool developed in our labs that enables simultaneous imaging of cerebral blood flow (CBF), cerebral blood volume, and tissue hemoglobin oxygenation, which allows us to monitor neurovascular and tissue metabolic activities at high spatiotemporal resolutions over a relatively large field of view. Moreover, we report digital frequency ramping Doppler optical coherence tomography (DFR-OCT) that allows for quantitative 3D imaging of the CBF network in vivo. In parallel, we review calcium imaging techniques to track neuronal activity, including intracellular calcium approach using Rhod2 fluorescence technique that we develop to detect neuronal activity in vivo. We report a new multimodality imaging platform that combines DW-LSI, DFR-OCT, and calcium fluorescence imaging for simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of the animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies suggest the potential of this multimodality approach for future awake animal and behavioral studies.

  1. Clinical features, risk factors, and outcome of cerebral venous thrombosis in Tehran, Iran

    PubMed Central

    Yadegari, Samira; Ghorbani, Askar; Miri, S. Roohollah; Abdollahi, Mohammad; Rostami, Mohsen

    2016-01-01

    Introduction: Despite increasing the use of magnetic resonance imaging (MRI), cerebral venous sinus thrombosis (CVST) has remained an under-diagnosed condition. In this study, characteristics and frequency of various risk factors of CVST patients in a tertiary referral hospital were closely assessed. Methods: Patients with an unequivocal diagnosis of CVST confirmed by MRI and magnetic resonance venography during 6 years of the study were included. All data from the onset of symptoms regarding clinical signs and symptoms, hospital admission, seasonal distribution, medical and drug history, thrombophilic profile, D-dimer, neuroimaging, cerebrospinal fluid findings, mortality, and outcome were collected and closely analyzed. Result: A total of 53 patients with female to male ratio of 3.07 and mean age of 33.7 years were included in the study. Headache and papilledema were the most frequent clinical features (44 and 36 patients, respectively). An underlying disease (diagnosed previously or after admission) was the most common identified risk factor for CVST in both females and males (21 patients). A total of 15 women used the oral contraceptive pill (OCP) where 12 of them had simultaneously other predisposing factors. Overall, 19 patients (36%) had more than one contributing factor. D-dimer had a sensitivity of 71.4% in CVST patients. The mortality of patients in this study was 3.7% (n = 2). Focal neurologic deficit and multicranial nerve palsy were associated with poor outcome which defined as death, recurrence, and massive intracranial hemorrhage due to anticoagulation (P = 0.050 and 0.004, respectively). Conclusion: Unlike most of the CVST studies in which OCP was the main factor; in this study, an underlying disease was the most identified cause. Considering the high probability of multiple risk factors in CVST that was shown by this study, appropriate work up should be noted to uncover them. PMID:27695236

  2. Non-invasive Quantification of Whole-brain Cerebral Metabolic Rate of Oxygen by MRI

    PubMed Central

    Xu, Feng; Ge, Yulin; Lu, Hanzhang

    2009-01-01

    Cerebral metabolic rate of oxygen (CMRO2) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO2 with Positron Emission Tomography (PET) or MRI involve special equipment and/or exogenous agent, and may not be suitable for routine clinical studies. In the present study, a non-invasive method is developed to estimate whole-brain CMRO2 in humans. This method applies phase-contrast MRI for quantitative blood flow measurement and T2-Relaxation-Under-Spin-Tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO2. Whole-brain averaged CMRO2 values in young, healthy subjects were 132.1±20.0 μmol/100g/min, in good agreement with literature reports using PET. Various acquisition strategies for phase-contrast and TRUST MRI were compared, and it was found that non-gated phase-contrast and sagittal sinus TRUST MRI were able to provide the most efficient and accurate estimation of CMRO2. In addition, blood flow and venous oxygenation were found to be positively correlated across subjects. Owing to the non-invasive nature of this method, it may be a convenient and useful approach for assessment of brain metabolism in brain disorders as well as under various physiologic conditions. PMID:19353674

  3. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    SciTech Connect

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H. )

    1991-03-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.

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

    PubMed Central

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

    2017-01-01

    Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male’s CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia. PMID:28262723

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

    PubMed

    Acaz-Fonseca, Estefanía; Ortiz-Rodriguez, Ana; Lopez-Rodriguez, Ana B; Garcia-Segura, Luis M; Astiz, Mariana

    2017-03-06

    Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.

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

    PubMed Central

    2012-01-01

    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. PMID:22738270

  7. Multiplexed MRI methods for rapid estimation of global cerebral metabolic rate of oxygen consumption.

    PubMed

    Lee, Hyunyeol; Langham, Michael C; Rodriguez-Soto, Ana E; Wehrli, Felix W

    2017-04-01

    The global cerebral metabolic rate of oxygen (CMRO2), which reflects metabolic activity of the brain under various physiologic conditions, can be quantified using a method, referred to as 'OxFlow', which simultaneously measures hemoglobin oxygen saturation in a draining vein (Yv) and total cerebral blood flow (tCBF). Conventional OxFlow (Conv-OxFlow) entails four interleaves incorporated in a single pulse sequence - two for phase-contrast based measurement of tCBF in the supplying arteries of the neck, and two to measure the intra- to extravascular phase difference in the superior sagittal sinus to derive Yv [Jain et al., JCBFM 2010]. However, this approach limits achievable temporal resolution thus precluding capture of rapid changes of brain metabolic states such as the response to apneic stimuli. Here, we developed a time-efficient, multiplexed OxFlow method and evaluated its potential for measuring dynamic alterations in global CMRO2 during a breath-hold challenge. Two different implementations of multiplexed OxFlow were investigated: 1) simultaneous-echo-refocusing based OxFlow (SER-OxFlow) and 2) simultaneous-multi-slice imaging-based dual-band OxFlow (DB-OxFlow). The two sequences were implemented on 3T scanners (Siemens TIM Trio and Prisma) and their performance was evaluated in comparison to Conv-OxFlow in ten healthy subjects for baseline CMRO2 quantification. Comparison of measured parameters (Yv, tCBF, CMRO2) revealed no significant bias of SER-OxFlow and DB-OxFlow, with respect to the reference Conv-OxFlow while improving temporal resolution two-fold (12.5 versus 25s). Further acceleration shortened scan time to 8 and 6s for SER and DB-OxFlow, respectively, for time-resolved CMRO2 measurement. The two sequences were able of capturing smooth transitions of Yv, tCBF, and CMRO2 over the time course consisting of 30s of normal breathing, 30s of volitional apnea, and 90s of recovery. While both SER- and DB-OxFlow techniques provide significantly improved

  8. Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury.

    PubMed Central

    Sharples, P M; Stuart, A G; Matthews, D S; Aynsley-Green, A; Eyre, J A

    1995-01-01

    Understanding the pathophysiology of paediatric head trauma is essential for rational acute management. It has been proposed that the response to severe head injury in children differs from that in adults, with increased cerebral blood flow (cerebral hyperaemia) representing the most common cause of raised intracranial pressure, but this has recently been disputed. The relation between the pathophysiological response and time after injury has not been defined in children. This paper describes 151 serial measurements of cerebral blood flow, arteriojugular venous oxygen difference (AJVDO2), and cerebral metabolic rate for oxygen (CMRO2) that were performed in 21 children with severe head injury, mean age 8 (range 2-16) years, Glasgow coma score < or = 8. Absolute cerebral hyperaemia was uncommon, only 10 (7%) of the 151 cerebral blood flow values being at or above the upper limit of the range published in normal children. There was an inverse correlation between cerebral blood flow and intracranial pressure. (r = -0.24, p = 0.009). Contrary to the widespread assumption that cerebral metabolic rate in patients with head injury is always low, CMRO2 was initially within the normal range in 17/21 (81%) children. Both CMRO2 and AJVDO2 fell significantly between the first and third days after injury. There was a non-significant rise in cerebral blood flow over time. These data represent the first evidence that the temporal change in cerebral metabolic rate reported in experimental models of traumatic brain injury also occurs in patients with head injury. The changes in the pathophysiological response over time suggest that the management may need to be modified accordingly. If cerebral metabolic rate and cerebral oxygen extraction are maximal shortly after injury in children with severe head injury then the children are most likely to sustain secondary damage during this period. Images PMID:7876842

  9. Statistical image analysis of cerebral glucose metabolism in patients with cognitive impairment following diffuse traumatic brain injury.

    PubMed

    Kato, Takayuki; Nakayama, Noriyuki; Yasokawa, Yuto; Okumura, Ayumi; Shinoda, Jun; Iwama, Toru

    2007-06-01

    The aim of this study was to explore the regional cerebral glucose metabolism (rCM) in patients with chronic stage traumatic brain injury (TBI) compared with normal controls. We also investigated the relationship between regional cerebral glucose metabolism and cognitive function. We performed 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) study using statistical parametric mapping (SPM) analysis in 36 diffuse axonal injury (DAI) patients (mean age +/- SD, 36.3 +/- 9.8 years). At 6 months or more after head injury, all patients underwent FDG-PET study and neuropsychological batteries to assess cognitive function. Thirty healthy, gender-matched control subjects who were comparable in age were also studied. Between the TBI patients and normal controls, group comparisons showed regional metabolic decreases in the bilateral frontal lobes, temporal lobes, thalamus, as well as the right cerebellum in the TBI group. Only full-scale Intelligence Quotient (IQ) (mean +/- SD, 78.5 +/- 11.9) correlated positively with rCM in the right cingulate gyrus and the bilateral medial frontal gyrus. In other examinations, the correlation was not provided. DAI may induce functional disconnection and decreased neuronal activity, and finally lead to diffuse glucose hypometabolism. Low full-scale IQ scores may be related to significantly different underlying cognitive impairment. In supporting cognitive function following TBI, which showed diffuse cerebral metabolic reduction compared with normal controls, medial prefrontal cortex and anterior cingulate cortex may be an important component.

  10. Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment.

    PubMed

    Brooks, George A; Martin, Neil A

    2014-01-01

    Because it is the product of glycolysis and main substrate for mitochondrial respiration, lactate is the central metabolic intermediate in cerebral energy substrate delivery. Our recent studies on healthy controls and patients following traumatic brain injury (TBI) using [6,6-(2)H2]glucose and [3-(13)C]lactate, along with cerebral blood flow (CBF) and arterial-venous (jugular bulb) difference measurements for oxygen, metabolite levels, isotopic enrichments and (13)CO2 show a massive and previously unrecognized mobilization of lactate from corporeal (muscle, skin, and other) glycogen reserves in TBI patients who were studied 5.7 ± 2.2 days after injury at which time brain oxygen consumption and glucose uptake (CMRO2 and CMRgluc, respectively) were depressed. By tracking the incorporation of the (13)C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls. Standard of care treatment of TBI patients in state-of-the-art facilities by talented and dedicated heath care professionals reveals presence of a catabolic Body Energy State (BES). Results are interpreted to mean that additional nutritive support is required to fuel the body and brain following TBI. Use of a diagnostic to monitor BES to provide health care professionals with actionable data in providing nutritive formulations to fuel the body and brain and achieve exquisite glycemic control are discussed. In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined. To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

  11. Impacts of small arteriovenous malformations (AVM) on regional cerebral blood flow and glucose metabolism

    SciTech Connect

    Liu, R.S.; Yeh, S.H.; Chu, L.S.

    1994-05-01

    This study assessed the effects of small AVMs (<3 cm) on the regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT and on the glucose metabolism (rCGlcM) by [F-18]-FDG PET. Seven AVM patients (pts) were studied. All AVMs were confirmed by cerebral angiography and CT/MR scans. Tc-99m HMPAO SPECT and [F-18]-PDG PET images were interpreted visually to detect the changes of rCBF and rCGlcM. All pts except one brain stem AVM had defects in the regions of nidi on HMPAO and FDG images. FDG PET disclosed low rCGlcM in surrounding areas of AVMs in 6 pts, while HMPAO SPECT detected only 4 cases. One AVM had increased rCBF surrounding the nidus despite of decreased rCGlcM in the same region. Five pts had abnormal rCGlcM over ipsilateral remote cortex but only one had corresponding abnormal rCBF. Contralateral cortical hypofunction was noted in 3 pts by FDG PET but none by HMPAO SPECT. Cross cerebellar diaschisis was found in 2 AVMs by FDG PET and only one by HMPAO SPECT. All regions with abnormal HMPAO uptake did not look as discernibly as seen on the FDG PET scan. CT/MR scans detected the nidi of AVMs of all pts and old hemorrhage in one pt. In conclusion, either HMPAO SPECT or FDG PET is sensitive to detect the functional abnormalities in the region of nidus of small AVM and the surrounding brain tissue. FDG PET is better than HMPAO SPECT to detect functional changes in the remote cortex and diaschisis.

  12. Quantitative Mapping of Cerebral Metabolic Rate of Oxygen (CMRO2) using Quantitative Susceptibility Mapping (QSM)

    PubMed Central

    Zhang, Jingwei; Liu, Tian; Gupta, Ajay; Spincemaille, Pascal; Nguyen, Thanh D.; Wang, Yi

    2014-01-01

    Purpose To quantitatively map cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction fraction (OEF) in human brains using quantitative susceptibility mapping (QSM) and arterial spin labeling measured cerebral blood flow (CBF) before and after caffeine vasoconstriction. Methods Using the multiecho 3D gradient echo sequence and an oral bolus of 200 mg caffeine, whole brain CMRO2 and OEF were mapped at 3mm isotropic resolution on 13 healthy subjects. The QSM based CMRO2 was compared with an R2* based CMRO2 to analyze the regional consistency within cortical gray matter (CGM) with the scaling in the R2* method set to provide same total CMRO2 as the QSM method for each subject. Results Compared to pre-caffeine, susceptibility increased (5.1±1.1ppb, p<0.01) and CBF decreased (−23.6±6.7ml/100g/min, p<0.01) at 25min post-caffeine in CGM. This corresponded to a CMRO2 of 153.0±26.4µmol/100g/min with an OEF of 33.9±9.6% and 54.5±13.2% (p<0.01) pre- and post- caffeine respectively at CGM, and a CMRO2 of 58.0±26.6µmol/100g/min at white matter. CMRO2 from both QSM and R2* based methods showed good regional consistency (p>0.05), but quantitation of R2* based CMRO2 required an additional scaling factor. Conclusion QSM can be used with perfusion measurements pre- and post- caffeine vascoconstriction to map CMRO2 and OEF. PMID:25263499

  13. Quantitative susceptibility mapping-based cerebral metabolic rate of oxygen mapping with minimum local variance.

    PubMed

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

    2017-03-10

    The objective of this study was to demonstrate the feasibility of a cerebral metabolic rate of oxygen (CMRO2 ) mapping method based on its minimum local variance (MLV) without vascular challenge using quantitative susceptibility mapping (QSM) and cerebral blood flow (CBF). Three-dimensional multi-echo gradient echo imaging and arterial spin labeling were performed in 11 healthy subjects to calculate QSM and CBF. Minimum local variance was used to compute whole-brain CMRO2 map from QSM and CBF. The MLV method was compared with a reference method using the caffeine challenge. Their agreement within the cortical gray matter (CGM) was assessed on CMRO2 and oxygen extraction fraction (OEF) maps at both baseline and challenge states. Mean CMRO2 (in µmol/100 g/min) obtained in CGM using the caffeine challenge and MLV were 142 ± 16.5 and 139 ± 14.8 µmol/100 g/min, respectively; the corresponding baseline OEF were 33.0 ± 4.0% and 31.8 ± 3.2%, respectively. The MLV and caffeine challenge methods showed no statistically significant differences across subjects with small ( < 4%) biases in CMRO2 and OEF values. Minimum local variance-based CMRO2 mapping without vascular challenge using QSM and arterial spin labeling is feasible in healthy subjects. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

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

    PubMed

    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

  15. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations.

    PubMed

    Simon, Aaron B; Dubowitz, David J; Blockley, Nicholas P; Buxton, Richard B

    2016-04-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2' as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2', we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2'-based estimate of the metabolic response to CO2 of 1.4%, and R2'- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2'-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2.

  16. A novel Bayesian approach to accounting for uncertainty in fMRI-derived estimates of cerebral oxygen metabolism fluctuations

    PubMed Central

    Simon, Aaron B.; Dubowitz, David J.; Blockley, Nicholas P.; Buxton, Richard B.

    2016-01-01

    Calibrated blood oxygenation level dependent (BOLD) imaging is a multimodal functional MRI technique designed to estimate changes in cerebral oxygen metabolism from measured changes in cerebral blood flow and the BOLD signal. This technique addresses fundamental ambiguities associated with quantitative BOLD signal analysis; however, its dependence on biophysical modeling creates uncertainty in the resulting oxygen metabolism estimates. In this work, we developed a Bayesian approach to estimating the oxygen metabolism response to a neural stimulus and used it to examine the uncertainty that arises in calibrated BOLD estimation due to the presence of unmeasured model parameters. We applied our approach to estimate the CMRO2 response to a visual task using the traditional hypercapnia calibration experiment as well as to estimate the metabolic response to both a visual task and hypercapnia using the measurement of baseline apparent R2′ as a calibration technique. Further, in order to examine the effects of cerebral spinal fluid (CSF) signal contamination on the measurement of apparent R2′, we examined the effects of measuring this parameter with and without CSF-nulling. We found that the two calibration techniques provided consistent estimates of the metabolic response on average, with a median R2′-based estimate of the metabolic response to CO2 of 1.4%, and R2′- and hypercapnia-calibrated estimates of the visual response of 27% and 24%, respectively. However, these estimates were sensitive to different sources of estimation uncertainty. The R2′-calibrated estimate was highly sensitive to CSF contamination and to uncertainty in unmeasured model parameters describing flow-volume coupling, capillary bed characteristics, and the iso-susceptibility saturation of blood. The hypercapnia-calibrated estimate was relatively insensitive to these parameters but highly sensitive to the assumed metabolic response to CO2. PMID:26790354

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

    PubMed

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

    PubMed Central

    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

  19. Evaluation of Oxidative Stress Parameters and Energy Metabolism in Cerebral Cortex of Rats Subjected to Sarcosine Administration.

    PubMed

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Kim, Tomas Duk Hwa; Zanatta, Ângela; Schmitz, Felipe; Rodrigues, André Felipe; Wyse, Angela T S; Wajner, Moacir; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2017-08-01

    Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats. Acute administration of sarcosine induced oxidative stress and diminished the activities of adenylate kinase, GAPDH, complex IV, and mitochondrial and cytosolic creatine kinase. On the other hand, succinate dehydrogenase activity was enhanced in cerebral cortex of rats. Moreover, total sulfhydryl content was significantly diminished, while DCFH oxidation, TBARS content, and activities of SOD and GPx were significantly enhanced by acute administration of sarcosine. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by sarcosine administration on the oxidative stress and the enzymes of phosphoryltransfer network. These results indicate that acute administration of sarcosine may stimulate oxidative stress and alter the energy metabolism in cerebral cortex of rats. In case these effects also occur in humans, they may contribute, along with other mechanisms, to the neurological dysfunction of sarcosinemia, and creatine and pyruvate supplementation could be beneficial to the patients.

  20. Cerebral Blood Flow and Glucose Metabolism Measured With Positron Emission Tomography Are Decreased in Human Type 1 Diabetes

    PubMed Central

    van Golen, Larissa W.; Huisman, Marc C.; Ijzerman, Richard G.; Hoetjes, Nikie J.; Schwarte, Lothar A.; Lammertsma, Adriaan A.; Diamant, Michaela

    2013-01-01

    Subclinical systemic microvascular dysfunction exists in asymptomatic patients with type 1 diabetes. We hypothesized that microangiopathy, resulting from long-standing systemic hyperglycemia and hyperinsulinemia, may be generalized to the brain, resulting in changes in cerebral blood flow (CBF) and metabolism in these patients. We performed dynamic [15O]H2O and [18F]-fluoro-2-deoxy-d-glucose brain positron emission tomography scans to measure CBF and cerebral glucose metabolism (CMRglu), respectively, in 30 type 1 diabetic patients and 12 age-matched healthy controls after an overnight fast. Regions of interest were automatically delineated on coregistered magnetic resonance images and full kinetic analysis was performed. Plasma glucose and insulin levels were higher in patients versus controls. Total gray matter CBF was 9%, whereas CMRglu was 21% lower in type 1 diabetic subjects versus control subjects. We conclude that at real-life fasting glucose and insulin levels, type 1 diabetes is associated with decreased resting cerebral glucose metabolism, which is only partially explained by the decreased CBF. These findings suggest that mechanisms other than generalized microangiopathy account for the altered CMRglu observed in well-controlled type 1 diabetes. PMID:23530004

  1. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    SciTech Connect

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

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

    PubMed Central

    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 (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic 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

  3. Regional Cerebral Glucose Metabolism and its Association with Phenotype and Cognitive Functioning in Patients with Autism

    PubMed Central

    Anil Kumar, B. N.; Malhotra, Savita; Bhattacharya, Anish; Grover, Sandeep; Batra, Y. K.

    2017-01-01

    Introduction: In spite of three decades of neuroimaging, we are unable to find consistent and coherent anatomical or pathophysiological basis for autism as changes are subtle and there are no studies from India. Aim: To study the regional cerebral glucose metabolism in children with autism using positron emission tomography (PET) scan and to study the behavior and cognitive functioning among them. Materials and Methods: Ten subjects (8–19 years) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for autism were evaluated on Childhood Autism Rating Scale (CARS), trail making test (TMT) A and B, Wisconsin card sorting test, Raven's progressive matrices, and PET scan. A control group of 15 matched subjects without any brain pathology or neurological disorder was similarly studied. Results: Four out of the ten patients with autism had abnormal PET scan findings, and in contrast, none of the patients in the control group had abnormal PET scan. Of the four patients with abnormality in the PET scan, two patients had findings suggestive of hypometabolism in cerebellum bilaterally; one patient showed bilateral hypometabolism in anterior temporal cortices and cerebellum, and the fourth patient had hypermetabolism in the bilateral frontal cortices and medial occipital cortices. Subjects with autism performed poorly on neuropsychological testing. Patients with abnormal PET scan findings had significantly higher scores on the “body use” domain of CARS indicating more stereotypy. Conclusion: Findings of this study support the view of altered brain functioning in subjects with autism. PMID:28615758

  4. The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism

    PubMed Central

    Jespersen, Sune N; Østergaard, Leif

    2012-01-01

    Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow (CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic–metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia–reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism. PMID:22044867

  5. Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

    SciTech Connect

    Baxter, L.R. Jr.; Phelps, M.E.; Mazziotta, J.C.; Schwartz, J.M.; Gerner, R.H.; Selin, C.E.; Sumida, R.M.

    1985-05-01

    Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.

  6. Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

    PubMed Central

    García-Cabezas, Miguel Á.; John, Yohan J.; Barbas, Helen; Zikopoulos, Basilis

    2016-01-01

    The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease. PMID:27847469

  7. Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression.

    PubMed

    Ampawong, Sumate; Chaisri, Urai; Viriyavejakul, Parnpen; Nontprasert, Apichart; Grau, Georges E; Pongponratn, Emsri

    2014-01-01

    The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.

  8. [Effect of normobaric hyperoxia on cerebral oxygenation, metabolism and oxidative stress in patients with subarachnoid hemorrhage caused by intracranial aneurysm rupture].

    PubMed

    Solodov, A A; Petrikov, S S; Klychnikova, E V; Tazina, E V; Krylov, V V; Godkov, M A; Khamidova, L T

    2013-01-01

    The development of cerebral vasospasm in subarachnoid hemorrhage (SAH) due to cerebral aneurysms rupture results in cerebral circulation disturbances. Application of normobaric hyperoxia can be an effective way for improving of oxygen delivery to injured brain tissues. The purpose of this study was to assess of normobaric hyperoxia influence on intracranial pressure (ICP), cerebral oxygenation and metabolism, oxidative stress and endogenous factors of vascular regulation in II critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture. Increase of FiO2 from 0.3 to 0.5 and 1.0 was accompanied with brain oxygen tension (PbrO2) increase and cerebral extraction ratio for oxygen (O2ER) decrease. Application of normobaric hyperoxia had no effect on ICP, cerebral perfusion pressure, arterial blood pressure and cerebral metabolism. The results obtained from patients with nontraumatic SAH showed an evident increase of oxidative stress which had a significant effect on vascular endothelial function, causing an imbalance in the endogenous regulation of vascular tone. Application of normobaric hyperoxia was not accompanied by an increase of free-radical processes in critically ill patients with nontraumatic SAH due to cerebral aneurysms rupture.

  9. [Clinical features of osteoarthritis in patients with metabolic syndrome].

    PubMed

    Vasilyeva, L V; Lakhin, D I

    To estimate clinical and laboratory parameters in patients with osteoarthritis (OA) and in those with OA and metabolic syndrome (MS). 164 patients with OA were examined and divided into 2 groups of 82 people: a study group (patients with MS) and a control one (those without MS). OA was defined according to the diagnostic criteria described by R.D. Althmann (1995). MS was identified based on the criteria developed by the International Diabetes Federation (2005). The location of affected and swollen joints was determined according to the Richie index; the intensity of pain syndrome was measured by a visual analogue scale at rest and on movement; the WOMAC and Lequesne indexes were estimated in the patients. Erythrocyte sedimentation rate and C-reactive protein and tumor necrosis factor-α levels were determined from laboratory data. In the MS group, the frequency of joint injuries at various sites, the prevalence of synovitis, and the intensity of pain and inflammation were significantly higher than in the non-MS group. The negative impact of MS on the clinical picture of OA can be inferred by the findings.

  10. Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms.

    PubMed

    Causton, Helen C; Feeney, Kevin A; Ziegler, Christine A; O'Neill, John S

    2015-04-20

    Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their internal state to anticipate and/or resonate with the external environment. Although ∼24-hr periodicity is observed across aerobic eukaryotes, the central mechanism has been hard to dissect because few simple models exist, and known clock proteins are not conserved across phylogenetic kingdoms. In contrast, contributions to circadian rhythmicity made by a handful of post-translational mechanisms, such as phosphorylation of clock proteins by casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3), appear conserved among phyla. These kinases have many other essential cellular functions and are better conserved in their contribution to timekeeping than any of the clock proteins they phosphorylate. Rhythmic oscillations in cellular redox state are another universal feature of circadian timekeeping, e.g., over-oxidation cycles of abundant peroxiredoxin proteins. Here, we use comparative chronobiology to distinguish fundamental clock mechanisms from species and/or tissue-specific adaptations and thereby identify features shared between circadian rhythms in mammalian cells and non-circadian temperature-compensated respiratory oscillations in budding yeast. We find that both types of oscillations are coupled with the cell division cycle, exhibit period determination by CK1 and GSK3, and have peroxiredoxin over-oxidation cycles. We also explore how peroxiredoxins contribute to YROs. Our data point to common mechanisms underlying both YROs and circadian rhythms and suggest two interpretations: either certain biochemical systems are simply permissive for cellular oscillations (with frequencies from hours to days) or this commonality arose via divergence from an ancestral cellular clock.

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

    PubMed Central

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

    2015-01-01

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

  12. Metabolic Features Across the Female Life Span in Women with PCOS.

    PubMed

    Sir-Petermann, Teresa; Echiburú, Bárbara; Crisosto, Nicolás; Maliqueo, Manuel; Bravo, Francisco Pérez

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine metabolic disorder and is presently considered a family pathology. It is associated with obesity, insulin resistance and metabolic syndrome. Racial, ethnic and environmental factors may be important in determining the clinical manifestations of this syndrome. Polycystic ovary syndrome is an exclusion diagnosis and, therefore, should be distinguished from the physiological changes typical for the age and from other hyperandrogenic disorders. Early diagnosis is important since this syndrome is associated with reproductive, oncologic and metabolic risks. Interestingly, the clinical features of this disorder may change throughout the lifespan of a PCOS woman, starting from adolescence to postmenopausal age. During the first decades of life the main features are in the reproductive area, while later in life metabolic abnormalities are more evident. While the assessment of insulin resistance is not part of the diagnosis of PCOS, it has been demonstrated that this metabolic component appears early in life and persists over time. Moreover during puberty and pregnancy, insulin resistance is exacerbated. Pregnancy represents an important stage, as the offspring of these patients may be reprogrammed and inherit some of the metabolic and reproductive features of their mothers. In the present review, we will focus on several metabolic aspects of the PCOS condition at different stages of life in a Chilean population.

  13. PET studies of changes in cerebral blood flow and oxygen metabolism after unilateral microembolization of the brain in anesthetized dogs.

    PubMed

    Weyne, J; De Ley, G; Demeester, G; Vandecasteele, C; Vermeulen, F L; Donche, H; Deman, J

    1987-01-01

    Cerebral blood flow and oxygen metabolism have been measured with the steady-state oxygen-15 technique and positron emission tomography in anesthetized dogs. Regional microembolization was induced by infusing Sephadex particles (diameter, 40 micron) into one of the common carotid arteries. In the first series of experiments, 2.5 mg Sephadex was infused, and the dogs were examined within 3-4 hours after embolization. In a second series 0.55 mg Sephadex was infused, and the dogs were examined either in the first 3-4 hours or 24-48 hours after embolization. Cerebral blood flow, oxygen extraction ratio, and cerebral oxygen utilization were measured at 3 PCO2 levels. In the acute experiments, cerebral oxygen utilization in the embolized hemisphere was 6 (0.55 mg Sephadex) and 25% (2.5 mg Sephadex) lower than on the contralateral side. While cerebral blood flow was symmetrically distributed in normocapnia and hypocapnia, it was 9 (0.55 mg Sephadex) and 35% (2.5 mg Sephadex) lower in the embolized hemisphere during hypercapnia. In normocapnia and hypocapnia the lower oxygen utilization in the embolized hemisphere was characterized by a lower oxygen extraction ratio, and in hypercapnia by an unchanged (0.55 mg Sephadex) or by a higher (2.5 mg Sephadex) extraction ratio. The different effect on oxygen extraction ratio in the control and embolized hemispheres resulted in images of uncoupling between perfusion and oxygen demand that varied according to the PCO2. The experiments also showed a fall in cerebral blood flow in the embolized hemisphere after 3-4 hours, indicating delayed hypoperfusion. After 24-48 hours, blood flow was about 10% higher in the embolized hemisphere, and this was observed at the 3 PCO2 levels, while the oxygen extraction ratio was systematically lower. Oxygen utilization in the embolized hemisphere was depressed to practically the same extent as in acute experiments. It can be concluded that between 4 and 24 hours after microembolization the cerebral

  14. Computer-aided classification of Alzheimer's disease based on support vector machine with combination of cerebral image features in MRI

    NASA Astrophysics Data System (ADS)

    Jongkreangkrai, C.; Vichianin, Y.; Tocharoenchai, C.; Arimura, H.; Alzheimer's Disease Neuroimaging Initiative

    2016-03-01

    Several studies have differentiated Alzheimer's disease (AD) using cerebral image features derived from MR brain images. In this study, we were interested in combining hippocampus and amygdala volumes and entorhinal cortex thickness to improve the performance of AD differentiation. Thus, our objective was to investigate the useful features obtained from MRI for classification of AD patients using support vector machine (SVM). T1-weighted MR brain images of 100 AD patients and 100 normal subjects were processed using FreeSurfer software to measure hippocampus and amygdala volumes and entorhinal cortex thicknesses in both brain hemispheres. Relative volumes of hippocampus and amygdala were calculated to correct variation in individual head size. SVM was employed with five combinations of features (H: hippocampus relative volumes, A: amygdala relative volumes, E: entorhinal cortex thicknesses, HA: hippocampus and amygdala relative volumes and ALL: all features). Receiver operating characteristic (ROC) analysis was used to evaluate the method. AUC values of five combinations were 0.8575 (H), 0.8374 (A), 0.8422 (E), 0.8631 (HA) and 0.8906 (ALL). Although “ALL” provided the highest AUC, there were no statistically significant differences among them except for “A” feature. Our results showed that all suggested features may be feasible for computer-aided classification of AD patients.

  15. Comparison of cerebral regional glucose metabolic relationships in resting and auditory stimulated states

    SciTech Connect

    Metter, E.J.; Riege, W.H.; Mazziotta, J.C.; Phelps, M.E.; Kuhl, D.E.

    1984-01-01

    FDG positron computed tomography has demonstrated strong correlations between high frontal and occipital glucose metabolism in normal resting subjects, which varied by age and were lost in Huntington's and Parkinson's Diseases. The studies raised the question whether the findings may be explained by anatomic and not metabolic factors. An approach to the issue was to examine subjects scanned under two states, where functional and not anatomic features would account for relationship differences. Seventeen subjects were identified who had scans under resting and auditory stimulated states. Measurements were taken from 12 brain regions and were expressed as percentage of mean metabolism. A principal components analysis of the resting state demonstrated 3 components (73% of variance), while the stimulated states showed 4 (79% of variance). The first resting factor related frontal, right posterior inferior frontal and superior temporal regions, while in the stimulated, the frontal associated with the occipital. The second resting factor related both angular gyri and posterior temporal, while the third related left posterior inferior frontal, superior temporal and right occipital. With stimulation both factors were replaced by three others. The change in the first factor and its presence in other subject groups points to a functional relationship between the regions. Comparison to previous studies suggest the frontal-occipital association may involve aspects of attention. The variability in other factors was similar to loose correlations noted in normal studies and may reflect the differential response to several tasks.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Exercise-induced hypertension in men with metabolic syndrome: anthropometric, metabolic, and hemodynamic features.

    PubMed

    Gaudreault, Valérie; Després, Jean-Pierre; Rhéaume, Caroline; Alméras, Natalie; Bergeron, Jean; Tremblay, Angelo; Poirier, Paul

    2013-02-01

    Metabolic syndrome is associated with increased cardiac morbidity. The aim of this study was to evaluate exercise-induced hypertension (EIH) in men with metabolic syndrome and to explore potential associations with anthropometric and metabolic variables. A total of 179 normotensive men with metabolic syndrome underwent a maximal symptom-limited treadmill test. Blood pressure was measured at 5-min rest prior to exercise testing (anticipatory blood pressure), at every 3 min during the exercise, and during the recovery period. EIH was defined as maximum systolic blood pressure (SBP) ≥220 mmHg and/or maximum diastolic blood pressure (DBP) ≥100 mmHg. Of the 179 men, 87 (47%) presented EIH. Resting blood pressure values at baseline were 127±10/83±6 mmHg in EIH and 119±9/80±6 mmHg (P=0.01 for both) in normal blood pressure responders to exercise. Anticipatory SBP and DPS were higher in the group with EIH (P=0.001). Subjects with EIH presented higher waist circumference (WC) (P<0.01), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) levels as well as insulin resistance (all P<0.05). Abdominal subcutaneous adipose tissue and total body fat mass were comparable between groups. Subjects with EIH had higher abdominal visceral adipose tissue (P<0.001). The best predictors of EIH were resting SBP and abdominal obesity. Each increment of 5 cm in WC was associated with an odds ratio of 1.30 (1.20-1.68) for EIH. About half of our subjects with metabolic syndrome showed EIH. These men are characterized by a worsened metabolic profile. Our data suggest that a treadmill exercise test may be helpful to identify a potentially higher risk metabolic syndrome subset of subjects.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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 mL O2/100 g/min between the two techniques over a range from 0.3 to 4 mL O2/100 g/min.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26618044

  1. Effect of ethanol on cerebral blood flow (CBF) and metabolism (CMRO2) in conscious sheep

    SciTech Connect

    Krasney, J.A.; Zubkov, B.; Iwamoto, J. )

    1991-03-11

    A moderate dose of ethanol severely depresses CBF and CMRO2 in the awake sheep fetus. However, the effects of ethanol on CBF and CMRO2 in the adult are unclear. The same dose of ethanol was infused for 2 hr in 5 ewes instrumented with aortic, left ventricular and sagittal sinus catheters. Ethanol caused ataxia accompanied by early modest and variable increases of total and regional CBF and CMRO2, followed by later modest and variable decreases of total and regional CBF (cerebellum) and CMRO2. Ethanol caused a cerebral transcapillary fluid shift as indicated by significant increases of the arterial-cerebral venous differences for hematocrit and hemoglobin. Brain wet-dry ratios increased by 10% above control levels. However, cerebral venous pressures were unchanged. The authors conclude that the adult cerebral response to ethanol differs quantitatively from that of the fetus. The functional significance of the cerebral fluid shift is unclear.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2003-08-07

    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 linger 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.

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

    PubMed

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

    2017-05-01

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

  5. Imaging Features of the Brain, Cerebral Vessels and Spine in Pediatric Tuberculous Meningitis With Associated Hydrocephalus.

    PubMed

    Rohlwink, Ursula K; Kilborn, Tracy; Wieselthaler, Nicky; Banderker, Ebrahim; Zwane, Eugene; Figaji, Anthony A

    2016-10-01

    Pediatric tuberculous meningitis (TBM) leads to high rates of mortality and morbidity. Prompt diagnosis and initiation of treatment are challenging; imaging findings play a key role in establishing the presumptive diagnosis. General brain imaging findings are well reported; however, specific data on cerebral vascular and spinal involvement in children are sparse. This prospective cohort study examined admission and followed up computed tomography brain scans and magnetic resonance imaging scans of the brain, cerebral vessels (magnetic resonance angiogram) and spine at 3 weeks in children treated for TBM with hydrocephalus (HCP; inclusion criteria). Exclusion criteria were no HCP on admission, treatment of HCP or commencement of antituberculosis treatment before study enrollment. Imaging findings were examined in association with outcome at 6 months. Forty-four patients (median age 3.3 [0.3-13.1] years) with definite (54%) or probable TBM were enrolled. Good clinical outcome was reported in 72%; the mortality rate was 16%. Infarcts were reported in 66% of patients and were predictive of poor outcome. Magnetic resonance angiogram abnormalities were reported in 55% of patients. Delayed tuberculomas developed in 11% of patients (after starting treatment). Spinal pathology was more common than expected, occurring in 76% of patients. Exudate in the spinal canal increased the difficulty of lumbar puncture and correlated with high cerebrospinal fluid protein content. TBM involves extensive pathology in the central nervous system. Severe infarction was predictive of poor outcome although this was not the case for angiographic abnormalities. Spinal disease occurs commonly and has important implications for diagnosis and treatment. Comprehensive imaging of the brain, spine and cerebral vessels adds insight into disease pathophysiology.

  6. Imaging Features of the Brain, Cerebral Vessels and Spine in Pediatric Tuberculous Meningitis with Associated Hydrocephalus

    PubMed Central

    Rohlwink, Ursula K; Kilborn, Tracy; Wieselthaler, Nicky; Banderker, Ebrahim; Zwane, Eugene; Figaji, Anthony A.

    2016-01-01

    Background Pediatric tuberculous meningitis leads to high rates of mortality and morbidity. Prompt diagnosis and initiation of treatment are challenging; imaging findings play a key role in establishing the presumptive diagnosis. General brain imaging findings are well reported; however, specific data on cerebral vascular and spinal involvement in children are sparse. Methods This prospective cohort study examined admission and follow up computed tomography brain scans and magnetic resonance imaging scans of the brain, cerebral vessels (magnetic resonance angiogram) and spine at 3 weeks in children treated for tuberculous meningitis with hydrocephalus (inclusion criteria). Exclusion criteria were no hydrocephalus on admission, treatment of hydrocephalus or commencement of anti-TB treatment before study enrolment. Imaging findings were examined in association with outcome at 6 months. Results Forty-four patients (median age 3.3 [0.3-13.1] years) with definite (54%) or probable tuberculous meningitis were enrolled. Good clinical outcome was reported in 72%; the mortality rate was 16%. Infarcts were reported in 66% of patients and were predictive of poor outcome. Magnetic resonance angiogram abnormalities were reported in 55% of patients. Delayed tuberculomas developed in 11% of patients (after starting treatment). Spinal pathology was more common than expected, occurring in 76% of patients. Exudate in the spinal canal increased the difficulty of lumbar puncture and correlated with high cerebrospinal fluid protein content. Conclusion Tuberculous meningitis involves extensive pathology in the central nervous system. Severe infarction was predictive of poor outcome although this was not the case for angiographic abnormalities. Spinal disease occurs commonly and has important implications for diagnosis and treatment. Comprehensive imaging of the brain, spine and cerebral vessels adds insight into disease pathophysiology. PMID:27213261

  7. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2014-07-15

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial-venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12-23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular 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, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. © 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  8. Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans

    PubMed Central

    Trangmar, Steven J; Chiesa, Scott T; Stock, Christopher G; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2014-01-01

    Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra-cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial–venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12–23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension () (R2 ≥ 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 and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction. PMID:24835170

  9. Leukoencephalopathy with cerebral calcifications and cysts: clinical and pathological features in two adults.

    PubMed

    Liu, Xuejun; Zheng, Xueping; Sui, Qinglan; Xu, Wenjian; Zee, Chi-Shing

    2016-03-01

    Two adult patients diagnosed with Leukoencephalopathy with cerebral calcifications and cysts (LCC) were presented. Both patients had a long-term (8-10 years) following-up. Radiological findings of both patients revealed the characteristic signs of LCC: cerebral white matter abnormalities, calcifications, and cysts. In case 1, the initial CT scan showed a low-density area in the right frontal lobe and it had developed into a large cystic lesion after 8 years. Histopathological determination revealed that the cyst wall was associated with hemorrhage, angiomatous formation, and some Rosenthal fibers. In case 2, a major cystic lesion was located at the left parietal lobe which was resected and an old hematoma was found inside the cyst. Nine years later, the follow-up neuroimaging of case 2 showed a remarkable improvement of white matter abnormalities and cystic lesions. Hemorrhagic fluid was observed inside the cysts. Additionally, follow-up CT and MR scans showed a rapid enlargement of cystic lesions accompanied with hemorrhagic fluid levels after a year. Then, a major cyst was surgically removed to relieve pressure symptoms. Pathology of the resected cyst exhibited an organized hemorrhage inside the cyst and a large amount of hemosiderin surrounding the cyst wall. In conclusion, our two cases demonstrated that angiomatous changes subsequent with hemorrhage may be the major mechanism of cyst formation and development.

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

    PubMed

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

    2017-09-01

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

  11. Evolutionary neuropathology & congenital mental retardation: environmental cues predictive of maternal deprivation influence the fetus to minimize cerebral metabolism in order to express bioenergetic thrift.

    PubMed

    Reser, Jared Edward

    2006-01-01

    This article will propose that humans have an adaptive vulnerability to certain forms of mental retardation, specifically, neuropathological disorders that cause decreased energy expenditure in the hippocampus and the cerebral cortex. This hypothesis will be analyzed in terms of the thrifty phenotype paradigm according to which adverse prenatal events can cause differential gene expression resulting in a phenotype that is better suited, metabolically, for a deprived environment. For example, a malnourished mother has an increased propensity to give birth to offspring that feature a "thrifty phenotype" which permits highly efficient calorie utilization, increased fat deposition and a sedentary nature. This article interprets several prenatal occurrences, including maternal malnourishment, low birth weight, multiparity, short birth interval, advanced maternal age and maternal stress--which are currently identified by the epidemiological literature as risk factors for neuropathology--to be environmental cues that communicate to the fetus that, because it will be neglected of maternal investment, developing a metabolically conservative brain will be the most effective ecological strategy. Success in hunting and foraging in mammals, primates and especially humans is known to be dependent on prolonged maternal investment. Low levels of maternal care are known to result in low survivorship of offspring, largely because the offspring are forced to subsist using simple, low-yield foraging strategies. A predictive, adaptive response, marked by cerebral hypometabolism, may produce a level of metabolic conservancy that mitigates the risks associated with low levels of maternal care. This article will suggest that certain, human neuropathological phenotypes would have been well suited for an ecological niche that closely resembled the less skill-intensive niche of our less encephalized, primate ancestors. The forms of congenital neuropathology discussed in this article do not

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

    PubMed Central

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

    2013-01-01

    The ratio of the changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) 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/CMRO2 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-CMRO2 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. PMID:23238435

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

    PubMed

    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.

  14. Bidirectional Relationships and Disconnects between NAFLD and Features of the Metabolic Syndrome.

    PubMed

    Wainwright, Patrick; Byrne, Christopher D

    2016-03-11

    Non-alcoholic fatty liver disease (NAFLD) represents a wide spectrum of liver disease from simple steatosis, to steatohepatitis, (both with and without liver fibrosis), cirrhosis and end-stage liver failure. NAFLD also increases the risk of hepatocellular carcinoma (HCC) and both HCC and end stage liver disease may markedly increase risk of liver-related mortality. NAFLD is increasing in prevalence and is presently the second most frequent indication for liver transplantation. As NAFLD is frequently associated with insulin resistance, central obesity, dyslipidaemia, hypertension and hyperglycaemia, NAFLD is often considered the hepatic manifestation of the metabolic syndrome. There is growing evidence that this relationship between NAFLD and metabolic syndrome is bidirectional, in that NAFLD can predispose to metabolic syndrome features, which can in turn exacerbate NAFLD or increase the risk of its development in those without a pre-existing diagnosis. Although the relationship between NAFLD and metabolic syndrome is frequently bidirectional, recently there has been much interest in genotype/phenotype relationships where there is a disconnect between the liver disease and metabolic syndrome features. Such potential examples of genotypes that are associated with a dissociation between liver disease and metabolic syndrome are patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) genotypes. This review will explore the bidirectional relationship between metabolic syndrome and NAFLD, and will also discuss recent insights from studies of PNPLA3 and TM6SF2 genotypes that may give insight into how and why metabolic syndrome features and liver disease are linked in NAFLD.

  15. The effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzymes in selenium and/or iodine deficient rats

    PubMed Central

    Caglayan, Aydan; Kocer-Gumusel, Belma; Erkekoglu, Pinar; Hincal, Filiz

    2016-01-01

    Objective(s): Particularly in developing countries, selenium and/or iodine deficiencies are encountered and use of pesticides in agriculture are not well-controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has applications against a wide range of pests. This study was designed to evaluate the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme activities in the presence of iodine and/or selenium deficiency on a rat model. Materials and Methods: Iodine and/or selenium deficiency was induced by feeding three-week-old Wistar rats with a diet containing <0.005 mg selenium kg-1, and/or administering 1% sodium perchlorate in drinking water for 7 weeks. Test groups received fenvalerate (100 mg kg-1 BW IP) for the last 7 days. Hepatic and cerebral microsomal aniline hydroxylase (CYP2E1) and cytosolic glutathione S-transferase (GST) activities were determined. Besides, hepatic NADPH-cytochrome P450 reductase (P450R), ethoxyresorufin O-deethylase (EROD, CYP1A1/1A2) and penthoxyresorufin O-depenthylase (PROD, CYP2B1/2B2), activities were also measured. Results: Fenvalerate had a general inductive effect on the hepatic and cerebral xenobiotic metabolizing enzyme activities. Moreover, enzyme activities were also altered by iodine and/or selenium deficiency, but the effects seemed to be enzyme- and tissue-specific. Conclusion: The inductive effect of fenvalerate, particularly in high dose exposures, may change the metabolism of several xenobiotics, including drugs, as well as endogenous substrates. The effects may vary depending on the selenium and/or iodine status of individual. PMID:27872699

  16. Age-related changes in ultrastructural features of cathepsin B- and D-containing neurons in rat cerebral cortex.

    PubMed

    Jung, H; Lee, E Y; Lee, S I

    1999-10-09

    The present study examines age-related changes in the subcellular localization of cathepsin B (cath B) and cathepsin D (cath D), as well as morphological features of the cathepsin-immunoreactive (ir) neurons in rat cerebral cortex. Sprague-Dawley rats were studied at 3 and 26 months. By immunoelectron microscopy cath B- or cath D-immunoreactivities were found in many, but not all, pyramidal neurons. In young rat cerebral cortical neurons, cath B was observed not only in lysosomal systems such as multivesicular bodies, dense bodies, and lipofuscin granules, but also in extralysosomal sites. By contrast, cath D was confined mainly to lysosomal systems in young rats. In aged rats, cath B showed a similar pattern in its subcellular localization compared to the young control, but some of the dense bodies containing cath B was closely apposed to the outer nuclear envelope. These cells exhibited a relatively normal appearance. Regardless of subcellular localization, approximately 10% of cath B-ir neurons displayed ultrastructural disturbances presumed to indicate an early stage of degeneration. The nucleus was indented, nuclear boundary was indistinct, nuclear pore structures appeared separately with high frequency, and the endoplasmic reticulum appeared to be affected. In addition to its presence in lysosomal structures, cath D-immunoreactivity in aged cerebral cortex was noted prominently in the cytosol as diffuse granules. About 37% of cath D-ir cells showed this age-related change. Among the neurons with the diffusely scattered form of cath D, approximately 70% of cells exhibited the degenerating features. These cells were characterized by large amounts of diffuse cath D, reduced cellular size, loss of the nuclear boundary, scattered nuclear pore structures, an often fragmentation of the nucleus, disturbances of endoplasmic reticular system, and in advanced stages, condensed nucleus and poor preservation of almost cytoplasmic organelles. Though some of these features

  17. Medium- and long-term effects of repeated bicuculline-induced seizures in developing rats on local cerebral energy metabolism.

    PubMed

    Doriat, J F; Koziel, V; Humbert, A C; Daval, J L

    1998-07-27

    To assess long-term metabolic consequences of recurrent ictal events arising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i.p. injections of bicuculline for three consecutive days, starting from postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cerebral metabolic rates for glucose were measured in 74 structures at P15, P25 and in adults (P60), by the autoradiographic method using 2-D-[14C]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reduction (16-34%) of glucose consumption at P15, mainly significant in sensory, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%). Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced metabolic rates for glucose (by 7-27%) at P25, significant in 23 structures, and depicting pronounced changes in limbic, hypothalamic, sensory and white matter areas, whereas brain functional activity finally returned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older animals, the reverse was true for long-term metabolic effects, and the more immature the brain when seizures arise, the more persistent the functional consequences.

  18. Cerebral coenurosis in a cat caused by Taenia serialis: neurological, magnetic resonance imaging and pathological features.

    PubMed

    Jull, Philip; Browne, Elizabeth; Boufana, Belgees S; Schöniger, Sandra; Davies, Emma

    2012-09-01

    CLINICAL SUMMARY: A 4-year-old Birman cat was presented with marked obtundation and non-ambulatory tetraparesis. Two well-demarcated, intra-axial T2-hyperintense, T1-hypointense structures, which did not contrast enhance, were evident on magnetic resonance imaging (MRI). Histopathology of the structures revealed metacestodes that were morphologically indicative of larval stages of Taenia species. Polymerase chain reaction amplification of a fragment within the 12S rRNA gene confirmed the subspecies as Taenia serialis. PRACTICAL SIGNIFICANCE: This is the first report of MRI findings of cerebral coenurosis caused by T serialis in a cat. Early MRI should be considered an important part of the diagnostic work-up for this rare clinical disease, as it will help guide subsequent treatment and may improve the prognosis.

  19. The value of anthropometric indices for identifying women with features of metabolic syndrome

    USDA-ARS?s Scientific Manuscript database

    BMI is a widely used anthropometric measure for identifying CVD and metabolic syndrome (MetS) risk. Two new anthropometric indices are A Body Shape Index (ABSI) and Body Roundness Index (BRI) that may provide better correlations to features of MetS. Methods: Subject data were obtained from 91 over...

  20. "Relevance vector machine" consciousness classifier applied to cerebral metabolism of vegetative and locked-in patients.

    PubMed

    Phillips, Christophe L; Bruno, Marie-Aurelie; Maquet, Pierre; Boly, Mélanie; Noirhomme, Quentin; Schnakers, Caroline; Vanhaudenhuyse, Audrey; Bonjean, Maxime; Hustinx, Roland; Moonen, Gustave; Luxen, André; Laureys, Steven

    2011-05-15

    The vegetative state is a devastating condition where patients awaken from their coma (i.e., open their eyes) but fail to show any behavioural sign of conscious awareness. Locked-in syndrome patients also awaken from their coma and are unable to show any motor response to command (except for small eye movements or blinks) but recover full conscious awareness of self and environment. Bedside evaluation of residual cognitive function in coma survivors often is difficult because motor responses may be very limited or inconsistent. We here aimed to disentangle vegetative from "locked-in" patients by an automatic procedure based on machine learning using fluorodeoxyglucose PET data obtained in 37 healthy controls and in 13 patients in a vegetative state. Next, the trained machine was tested on brain scans obtained in 8 patients with locked-in syndrome. We used a sparse probabilistic Bayesian learning framework called "relevance vector machine" (RVM) to classify the scans. The trained RVM classifier, applied on an input scan, returns a probability value (p-value) of being in one class or the other, here being "conscious" or not. Training on the control and vegetative state groups was assessed with a leave-one-out cross-validation procedure, leading to 100% classification accuracy. When applied on the locked-in patients, all scans were classified as "conscious" with a mean p-value of .95 (min .85). In conclusion, even with this relatively limited data set, we could train a classifier distinguishing between normal consciousness (i.e., wakeful conscious awareness) and the vegetative state (i.e., wakeful unawareness). Cross-validation also indicated that the clinical classification and the one predicted by the automatic RVM classifier were in accordance. Moreover, when applied on a third group of "locked-in" consciously aware patients, they all had a strong probability of being similar to the normal controls, as expected. Therefore, RVM classification of cerebral metabolic

  1. Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury.

    PubMed

    Cottenceau, Vincent; Masson, Francoise; Mahamid, Eugenia; Petit, Laurent; Shik, Venyamin; Sztark, Francois; Zaaroor, Menashe; Soustiel, Jean Francois

    2011-10-01

    The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

  2. CEREBRAL CORTICAL MICROVASCULAR RAREFACTION IN METABOLIC SYNDROME IS DEPENDENT ON INSULIN RESISTANCE AND LOSS OF NITRIC OXIDE BIOAVAILABILITY

    PubMed Central

    Chantler, Paul D.; Shrader, Carl D.; Tabone, Lawrence E.; d’Audiffret, Alexandre C.; Huseynova, Khumara; Brooks, Steven D.; Branyan, Kayla W.; Grogg, Kristin A.; Frisbee, Jefferson C.

    2015-01-01

    Objective Chronic presentation of the metabolic syndrome (MS) is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical microvascular density (MVD) may represent a central determinant of stroke outcomes. Methods This study used the obese Zucker rat (OZR) model of MS and clinically-relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors. Results OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with anti-hypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition. Conclusions Further analyses revealed that the maintenance of glycemic control and vascular nitric oxide bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions. PMID:26014499

  3. Differential regulation of sphingolipid metabolism in plasma, hippocampus, and cerebral cortex of mice administered sphingolipid modulating agents.

    PubMed

    Giles, Corey; Takechi, Ryusuke; Mellett, Natalie A; Meikle, Peter J; Dhaliwal, Satvinder; Mamo, John C

    2017-05-01

    Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (i) peripheral disturbances in sphingolipid concentrations are reflective of processes occurring in the brain, or (ii) circulating sphingolipids directly influence cerebral sphingolipid abundance. In order to address these assumptions, this study explores, in a physiological system, the metabolic pathways regulating sphingolipid metabolism in the brain and plasma of mice. Male C57Bl/6 were maintained on a low fat (control diet) or saturated fat enriched (SFA) diet with, or without the provision of sphingolipid modulating agents. Following 6 months of feeding, the abundance of seven sphingolipid classes was assessed by LC-ESI-MS/MS in the hippocampus (HPF), cerebral cortex (CTX), and plasma. Long-term consumption of the SFA diet increased ceramide and dihydroceramide in the plasma. Inhibiting de novo synthesis ameliorated this effect, while inhibition of acidic sphingomyelinase, or the sphingosine-1-phosphate receptor agonist did not. SFA feeding did not influence sphingolipid levels in either the HPF or CTX. De novo synthesis inhibition reduced ceramide in the CTX, while treatment with a sphingosine-1-phosphate receptor agonist reduced ceramides in the HPF. Analysis of the individual ceramide species revealed the effects were chain-length dependent. Both positive and negative correlations were observed between plasma and HPF/CTX ceramide species. The findings in this study show that HPF and CTX sphingolipid concentration are influenced by distinct pathways, independent of peripheral sphingolipid concentration. © 2017 International Society for Neurochemistry.

  4. Energy metabolism of cerebral mitochondria during aging, ischemia and post-ischemic recovery assessed by functional proteomics of enzymes.

    PubMed

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

    2013-12-01

    Stroke is a leading cause of death and disability, but most of the therapeutic approaches failed in clinical trials. The energy metabolism alterations, due to marked ATP decline, are strongly related to stroke and, at present, their physiopathological roles are not fully understood. Thus, the aim of this study was to evaluate the effects of aging on ischemia-induced changes in energy mitochondrial transduction and the consequences on overall brain energy metabolism in an in vivo experimental model of complete cerebral ischemia of 15min duration and during post-ischemic recirculation after 1, 24, 48, 72 and 96h, in 1year "adult" and 2year-old "aged" rats. The maximum rate (Vmax) of citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase and cytochrome oxidase for electron transfer chain (ETC) were assayed in non-synaptic "free" mitochondria and in two populations of intra-synaptic mitochondria, i.e., "light" and "heavy" mitochondria. The catalytic activities of enzymes markedly differ according to: (a) mitochondrial type (non-synaptic, intra-synaptic), (b) age, (c) acute effects of ischemia and (d) post-ischemic recirculation at different times. Enzyme activities changes are injury maturation events and strictly reflect the bioenergetic state of the tissue in each specific experimental condition respect to the energy demand, as shown by the comparative evaluation of the energy-linked metabolites and substrates content. Remarkably, recovery of mitochondrial function was more difficult for intra-synaptic mitochondria in "aged" rats, but enzyme activities of energy metabolism tended to normalize in all mitochondrial populations after 96h of recirculation. This observation is relevant for Therapy, indicating that mitochondrial enzymes may be important metabolic factors for the responsiveness of ischemic penumbra towards the restore of cerebral functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Specific features of sensorimotor cerebral cortex activity modulation by dopamine releaser amantadine.

    PubMed

    Storozhuk, Viktor M; Zinyuk, Larissa E

    2007-09-01

    The modulatory effects of amantadine (1-adamantanamine) on the activity of sensorimotor cerebral cortex neurones during microiontophoretic application of agonists of glutamatergic and GABA-ergic (gamma-aminobutyric acid) transmission were studied. In non-anaesthetised cats, dopamine (DA) released by amantadine application in a small area of the neocortex increased baseline and evoked neuronal activity, providing stabilization and optimum course of both the neuronal and the conditioned responses of the animal. Amantadine eliminates a decrease in the level of neuronal baseline and evoked activity and marked increase in the latency of neuronal activation and conditioned movement mediated by D2 receptor antagonist sulpiride ((S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoamantadineybenzamide) or GABA. This is reflected by a proportionate decrease in the onset of neuronal impulse reaction and latency of conditioned movement. Combined NMDA (N-methyl-D: -aspartate) and amantadine application also caused a considerable increase in baseline and evoked activity, but produced a slightly weaker effect than that evoked by NMDA application alone. A decrease in the baseline and evoked neuronal activity after NMDA withdrawn lasted during next control session (up to 40 min). The ability of DA releaser amantadine to alleviate significant increase in the latency of neuronal responses and conditioned movement induced by sulpiride or GABA suggests that dopamine modulates the activity of GABA-ergic inhibitory fast spike interneurons in the cat sensorimotor cortex during conditioning.

  6. Modifications of the expression of genes involved in cerebral cholesterol metabolism in the rat following chronic ingestion of depleted uranium.

    PubMed

    Racine, Radjini; Gueguen, Yann; Gourmelon, Patrick; Veyssiere, Georges; Souidi, Maâmar

    2009-06-01

    Depleted uranium results from the enrichment of natural uranium for energetic purpose. Its potential dispersion in the environment would set human populations at risk of being contaminated through ingestion. Uranium can build up in the brain and induce behavior disorders. As a major constituent of the myelin sheath, cholesterol is essential to brain function, and several neurological pathologies result from a disruption of cholesterol metabolism. To assess the effect of a chronic contamination with depleted uranium on cerebral cholesterol metabolism, rats were exposed to depleted uranium for 9 months through drinking water at 40 mg/l. The study focuses on gene expression. Cholesterol-catabolizing enzyme CYP46A1 displayed a 39% increase of its messenger RNA (mRNA) level. 3-Hydroxy-3-methylglutamyl CoA synthase gene expression rose from 91%. Concerning cholesterol transport, mRNA levels of scavenger receptor-B1 and adenosine triphosphate-binding cassette transporter A1 increased by 34% and that of apolipoprotein E by 75%. Concerning regulation, gene expression of nuclear receptors peroxisome proliferator-activated receptors alpha and gamma increased by 46% and 36% respectively, whereas that of retinoid-X-receptor decreased by 29%. In conclusion, a chronic internal contamination with depleted uranium does not affect the health status of rats but induces molecular changes in the dynamic equilibrium of the cerebral cholesterol pool.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate.

    PubMed

    Shidahara, Miho; Watabe, Hiroshi; Kim, Kyeong Min; Kudomi, Nobuyuki; Ito, Hiroshi; Iida, Hidehiro

    2008-10-01

    Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) can be estimated from C15O, H(2)15O, and 15O2 tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for 15O2 gas study for accurate estimation of OEF and CMRO2. We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO2 using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF=20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO2 from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBFg and CBFw) was 80 and 20, OEF in gray and white matter (Eg and Ew) was 0.4 and 0.3, (ii) CBFg and CBFw decreased by 50%, and Eg and Ew increased by 50% when compared with conditions (i) and (iii). CBFg and CBFw decreased by 80%, and Eg and Ew increased by 50% when compared with condition (i). The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO2, 3 min of scan time was desirable. The optimal scan time of 15O2 inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO2.

  9. Staphylococcus aureus small colony variants show common metabolic features in central metabolism irrespective of the underlying auxotrophism.

    PubMed

    Kriegeskorte, André; Grubmüller, Stephanie; Huber, Claudia; Kahl, Barbara C; von Eiff, Christof; Proctor, Richard A; Peters, Georg; Eisenreich, Wolfgang; Becker, Karsten

    2014-01-01

    In addition to the classical phenotype, Staphylococcus aureus may exhibit the small colony-variant (SCV) phenotype, which has been associated with chronic, persistent and/or relapsing infections. SCVs are characterized by common phenotypic features such as slow growth, altered susceptibility to antibiotic agents and pathogenic traits based on increased internalization and intracellular persistence. They show frequently auxotrophies mainly based on two different mechanisms: (i) deficiencies in electron transport as shown for menadione- and/or hemin-auxotrophs and (ii) thymidylate biosynthetic-defective SCVs. To get a comprehensive overview of the metabolic differences between both phenotypes, we compared sets of clinically derived menadione-, hemin- and thymidine-auxotrophic SCVs and stable site directed mutants exhibiting the SCV phenotype with their corresponding isogenic parental strains displaying the normal phenotype. Isotopologue profiling and transcriptional analysis of central genes involved in carbon metabolism, revealed large differences between both phenotypes. Labeling experiments with [U-(13)C6]glucose showed reduced (13)C incorporation into aspartate and glutamate from all SCVs irrespective of the underlying auxotrophism. More specifically, these SCVs showed decreased fractions of (13)C2-aspartate and glutamate; (13)C3-glutamate was not detected at all in the SCVs. In comparison to the patterns in the corresponding experiment with the classical S. aureus phenotype, this indicated a reduced carbon flux via the citric acid cycle in all SCV phenotypes. Indeed, the aconitase-encoding gene (acnA) was found down-regulated in all SCV phenotypes under study. In conclusion, all SCV phenotypes including clinical isolates and site-directed mutants displaying the SCV phenotype were characterized by down-regulation of citric acid cycle activity. The common metabolic features in central carbon metabolism found in all SCVs may explain similar characteristics of the S

  10. Acute Convexity Subarachnoid Hemorrhage Related to Cerebral Amyloid Angiopathy: Clinicoradiological Features and Outcome.

    PubMed

    Calviere, Lionel; Cuvinciuc, Victor; Raposo, Nicolas; Faury, Alexandre; Cognard, Christophe; Larrue, Vincent; Viguier, Alain; Bonneville, Fabrice

    2016-05-01

    The specificities of acute convexity subarachnoid hemorrhage (cSAH) related to cerebral amyloid angiopathy (CAA) and its evolution are not well known. We aimed to describe the clinicoradiological pattern, the magnetic resonance imaging (MRI) evolution, and the risk of recurrent bleeding in such patients. Among consecutive patients with an acute nontraumatic cSAH, subjects with available MRI who meet the modified Boston criteria for probable CAA were included. Review of medical records, MRI findings, and follow-up data was performed. Twenty-three patients (14 women; mean age ± standard deviation: 75.9 ± 7.3 years) were included. cSAH was revealed by transient focal neurological episodes (TFNEs) in 18 of 23 (78.3%) patients. In all patients, acute cSAH appeared as a sulcal fluid-attenuated inversion recovery hyperintensity and GRE T2 hypointensity. Cortical superficial siderosis and cortical microbleeds, respectively, were observed in 21 (91.3%) and 20 (86.9%) patients. Twenty patients (87%) had available follow-up data with a mean duration of 29.8 ± 20.2 months. Recurrent TFNEs occurred in 40% of patients. Acute cSAH evolved into cortical superficial siderosis in all patients. New subarachnoid bleedings defined by recurrent acute cSAH (n = 8) or extension of siderosis (n = 14) were detected in 83.3% of the patients. Lobar intracerebral hemorrhage (ICH) occurred in 7 patients (35%). CAA-related cSAH has a specific pattern defined by a high prevalence of TFNEs and cortical superficial siderosis, with a high risk of recurrent bleeding, either cSAH or lobar ICH. The systematic evolution from cSAH to focal cortical superficial siderosis reveals data on siderosis physiopathology. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

    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

  12. [Ten-years records of organic arsenic (diphenylarsinic acid) poisoning: epidemiology, clinical feature, metabolism, and toxicity].

    PubMed

    Ishi, Kazuhiro; Tamaoka, Akira

    2015-01-01

    We report here the symptoms of diphenylarsinic acid (DPAA) poisoning recorded over 10 years since the DPAA contamination of the potable well water was first detected in the Kamisu City, Ibaraki Prefecture, in 2003. The poisoning symptoms associated with the cerebellum and brainstem included nystagmus, tremors, myoclonus, and cerebellar ataxia as well as the symptoms associated with the temporal and occipital lobes such as memory impairment, sleep disorder, and visual disturbance. Some of the affected children exhibited mental retardation. Moreover, reduced blood flow and reduced glucose metabolism in the cerebella, brainstem, and temporal and occipital lobes persisted for several years among the DPAA-exposed persons. Based on the animal studies for DPAA intoxication, the target organs for the DPAA toxicity were determined to be the central nervous system (CNS), liver, and biliary system. In particular, DPAA tends to persist in the brain for a long time, resulting in long-term impacts on the brain. The cerebral blood flow and brain glucose metabolism, which can be measured by positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, are useful objective clinical markers to determine the effect of DPAA on CNS. We believe that continuous monitoring of the DPAA-exposed people may promote the effect of carcinogen and accelerate brain aging.

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

    PubMed

    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.

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

    PubMed

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

    2014-12-02

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

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

    PubMed Central

    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

  16. Post-traumatic hypoxia exacerbates neurological deficit, neuroinflammation and cerebral metabolism in rats with diffuse traumatic brain injury

    PubMed Central

    2011-01-01

    Background The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles. Methods Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O2/88% N2) or normoxic (22% O2/78% N2) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique. Results TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1β and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels. Conclusion Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction. PMID

  17. Using near-infrared spectroscopy to measure cerebral metabolic rate of oxygen under multiple levels of arterial oxygenation in piglets.

    PubMed

    Tichauer, Kenneth M; Elliott, Jonathan T; Hadway, Jennifer A; Lee, David S; Lee, Ting-Yim; St Lawrence, Keith

    2010-09-01

    Improving neurological care of neonates has been impeded by the absence of suitable techniques for measuring cerebral hemodynamics and energy metabolism at the bedside. Currently, near-infrared spectroscopy (NIRS) appears to be the technology best suited to fill this gap, and techniques have been proposed to measure both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). We have developed a fast and reliable bolus-tracking method of determining CMRO2 that combines measurements of CBF and cerebral venous oxygenation [venous oxygen saturation (CSvO2)]. However, this method has never been validated at different levels of arterial oxygenation [arterial oxygen saturation (SaO2)], which can be highly variable in the clinical setting. In this study, NIRS measurements of CBF, CSvO2, and CMRO2 were obtained over a range of SaO2 in newborn piglets (n=12); CSvO2 values measured directly from sagittal sinus blood samples were collected for validation. Two alternative NIRS methods that measure CSvO2 by manipulating venous oxygenation (i.e., head tilt and partial venous occlusion methods) were also employed for comparison. Statistically significant correlations were found between each NIRS technique and sagittal sinus blood oxygenation (P<0.05). Correlation slopes were 1.03 (r=0.91), 0.73 (r=0.73), and 0.73 (r=0.81) for the bolus-tracking, head tilt, and partial venous occlusion methods, respectively. The bolus-tracking technique displayed the best correlation under hyperoxic (SaO2=99.9±0.03%) and normoxic (SaO2=86.9±6.6%) conditions and was comparable to the other techniques under hypoxic conditions (SaO2=40.7±9.9%). The reduced precision of the bolus-tracking method under hypoxia was attributed to errors in CSvO2 measurement that were magnified at low SaO2 levels. In conclusion, the bolus-tracking technique of measuring CSvO2, and therefore CMRO2, is accurate and robust for an SaO2>50% but provides reduced accuracy under more severe hypoxic levels.

  18. Effects of anesthesia and recovery from ketamine racemate and enantiomers on regional cerebral glucose metabolism in rats.

    PubMed

    Freo, Ulderico; Ori, Carlo

    2004-05-01

    Unlike most anesthetics, ketamine racemate (S, R (+/-)-ketamine) induces heterogenous changes in cerebral metabolism. S, R (+/-)-ketamine is an equimolar mixture of two enantiomers, S (+)-ketamine and R (-)-ketamine, which differ in affinity for neuroreceptors and pharmacologic activities. This study investigated comparatively the effects of ketamine racemate and enantiomers on cerebral metabolism. Regional cerebral metabolic rates for glucose (rCMRglc) were determined with the quantitative, autoradiographic [C]2-deoxy-d-glucose technique in 40 brain regions of Fischer-344 rats. rCMRglc were measured in three groups of rats during equimolar anesthesia, 10 min after intraperitoneal injection of 170 mg/kg S, R (+/-)-ketamine, S (+)-ketamine, or R (-)-ketamine; in three groups of rats during recovery from equivalent anesthesia, 20 min after intravenous injection of 20, 12.5, and 30 mg/kg S, R (+/-)-ketamine, S (+)-ketamine, or R (-)-ketamine; and in two groups of saline-injected control rats. S, R (+/-)-ketamine and S (+)-ketamine induced a sustained anesthesia; deep rCMRglc decreases in 22 and 14 cortical, thalamic, cerebellar, and brainstem regions; and rCMRglc increases in two limbic regions (average decreases, 23 and 15%). R (-)-ketamine determined a shorter anesthesia, lesser rCMRglc decreases in 11 brain areas, and marked rCMRglc increases in 14 basal ganglia and limbic regions (average decrease, 4%). S, R (+/-)-ketamine, S (+)-ketamine, and R (-)-ketamine all produced postanesthetic behavioral activation; widespread rCMRglc increases in 28, 16, and 20 cortical, thalamic, basal ganglia, limbic, and brainstem regions; and rCMRglc decreases in few auditory and limbic regions (average increases, 35, 13, and 20%). S, R (+/-)-ketamine and S (+)-ketamine anesthesia but not R (-)-ketamine anesthesia induced widespread rCMRglc reductions that were unreported but are typical of gaseous and intravenous general anesthetics. Postanesthetic recovery led to divergent, sharp

  19. Characterization of the interaction between local cerebral metabolic rate for glucose and acid-base index in ischemic rat brain employing a double-isotope methodology

    SciTech Connect

    Peek, K.E.H.

    1988-01-01

    The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH-the acid-base index (ABI)-concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ({sup 14}C)2-deoxyglucose and ({sup 14}C)dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices.

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

    PubMed

    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

  1. Relation of EEG alpha background to cognitive fuction, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes

    SciTech Connect

    Devinsky, O.; Sato, S.; Conwit, R.A.; Schapiro, M.B. )

    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.

  2. The Effects of Conditions of Cerebral Anoxia, on Phospholipids, Metabolism, and Circulation of the Brain.

    DTIC Science & Technology

    Anoxia, *Phospholipids, Blood circulation, Pathology, Blood plasma , Erythrocytes, Patients, Metabolism, Blood chemistry, Brain, Experimental data, Dogs, Laboratory animals, Tables(Data), Blood diseases

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

    PubMed

    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.

  4. Cannabis dependence: Effects of cannabis consumption on inter-regional cerebral metabolic relationships in an Indian population.

    PubMed

    Parkar, Shubhangi R; Ramanathan, Seethalakshmi; Nair, Narendra; Batra, Shefali A; Adarkar, Shilpa A; Pandit, Anirudh G; Kund, Purushottam; Baghel, Nawab Singh

    2010-07-01

    The effects of cannabis consumption on neurophysiological function have been a matter of considerable debate. With the legalization of medical marijuana, understanding the consequences of cannabis dependence has become extremely important. We attempted to understand the influence of cannabis on cerebral glucose metabolism in certain predetermined regions of interest (ROIs). Furthermore, we also explored inter-regional metabolic relationships between ROIs forming the "addiction" and "cognitive dysmetria" circuit. 2-fluoro, 2-deoxy-glucose positron emission tomography (FDG PET) scans were carried out in 16 male patients (age: 25.3±10.38 years) with cannabis dependence, 8-12 hours after the last cannabis consumption. Resting glucose uptake in 14 pre-determined ROIs was compared with glucose uptake in 16 non-drug using volunteers (age: 29.2±8.39 years). The two groups differed in their lateral and medial temporal glucose uptakes by approximately 16-24%. The relationships between inter-regional glucose uptakes in the two circuits were compared using the Chow Test. Significant differences in inter-regional correlations in the medial temporo-frontal and parieto-thalamic were noted between the two groups. The altered metabolic relationships among various brain regions can have potentially important implications for understanding cannabis dependence and cannabis-induced psychopathology.

  5. Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Komatsu, K.; Takada, G.; Uemura, K.; Shishido, F.; Kanno, I. )

    1990-09-01

    We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using {sup 18}F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.

  6. Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance.

    PubMed

    Jelinek, David; Millward, Veronica; Birdi, Amandip; Trouard, Theodore P; Heidenreich, Randall A; Garver, William S

    2011-01-15

    A recent population-based genome-wide association study has revealed that the Niemann-Pick C1 (NPC1) gene is associated with early-onset and morbid adult obesity. Concurrently, our candidate gene-based mouse growth study performed using the BALB/cJ NPC1 mouse model (Npc1) with decreased Npc1 gene dosage independently supported these results by suggesting an Npc1 gene-diet interaction in relation to early-onset weight gain. To further investigate the Npc1 gene in relation to weight gain and metabolic features associated with insulin resistance, we interbred BALB/cJ Npc1(+/-) mice with wild-type C57BL/6J mice, the latter mouse strain commonly used to study aspects of diet-induced obesity and insulin resistance. This breeding produced a hybrid (BALB/cJ-C57BL/6J) Npc1(+/-) mouse model with increased susceptibility to weight gain and insulin resistance. The results from our study indicated that these Npc1(+/-) mice were susceptible to increased weight gain characterized by increased whole body and abdominal adiposity, adipocyte hypertrophy and hepatic steatosis in the absence of hyperphagia. Moreover, these Npc1(+/-) mice developed abnormal metabolic features characterized by impaired fasting glucose, glucose intolerance, hyperinsulinemia, hyperleptinemia and dyslipidemia marked by an increased concentration of cholesterol and triacylglycerol associated with low-density lipoprotein and high-density lipoprotein. The overall results are consistent with a unique Npc1 gene-diet interaction that promotes both weight gain and metabolic features associated with insulin resistance. Therefore, the NPC1 gene now represents a previously unrecognized gene involved in maintaining energy and metabolic homeostasis that will contribute to our understanding concerning the current global epidemic of obesity and type 2 diabetes mellitus.

  7. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression

    PubMed Central

    Conway, Charles R.; Chibnall, John T.; Gebara, Marie Anne; Price, Joseph L.; Snyder, Abraham Z.; Mintun, Mark A.; (Bud) Craig, A.D.; Cornell, Martha E.; Perantie, Dana C.; Giuffra, Luis A.; Bucholz, Richard D.; Sheline, Yvette I.

    2014-01-01

    Background Vagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD. Objective 17Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months. Methods Thirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders. Results A significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (Puncorrected = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders. Conclusions/Limitations VNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications. PMID:23485649

  8. Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review.

    PubMed

    Amiot, M J; Riva, C; Vinet, A

    2016-07-01

    Dietary polyphenols constitute a large family of bioactive substances potential beneficial effect on metabolic syndrome (MetS). This review summarizes the results of clinical studies on patients with MetS involving the chronic supplementation of a polyphenol-rich diet, foods, extracts or with single phenolics on the features of MetS (obesity, dyslipidemia, blood pressure and glycaemia) and associated complications (oxidative stress and inflammation). Polyphenols were shown to be efficient, especially at higher doses, and there were no specific foods or extracts able to alleviate all the features of MetS. Green tea, however, significantly reduced body mass index and waist circumference and improved lipid metabolism. Cocoa supplementation reduced blood pressure and blood glucose. Soy isoflavones, citrus products, hesperidin and quercetin improved lipid metabolism, whereas cinnamon reduced blood glucose. In numerous clinical studies, antioxidative and anti-inflammatory effects were not significant after polyphenol supplementation in patients with MetS. However, some trials pointed towards an improvement of endothelial function in patients supplemented with cocoa, anthocyanin-rich berries, hesperidin or resveratrol. Therefore, diets rich in polyphenols, such as the Mediterranean diet, which promote the consumption of diverse polyphenol-rich products could be an effective nutritional strategy to improve the health of patients with MetS. © 2016 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

  9. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice.

    PubMed

    Carlström, Mattias; Larsen, Filip J; Nyström, Thomas; Hezel, Michael; Borniquel, Sara; Weitzberg, Eddie; Lundberg, Jon O

    2010-10-12

    The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.

  10. Chronological Trends in Clinical and Urinary Metabolic Features over 20 Years in Korean Urolithiasis Patients.

    PubMed

    Kang, Ho Won; Seo, Sung Pil; Ha, Yun Sok; Kim, Won Tae; Kim, Yong June; Yun, Seok Joong; Kim, Wun Jae; Lee, Sang Cheol

    2017-09-01

    Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996-2000, n = 897), group 2 (2001-2005, n = 1,018), group 3 (2006-2010, n = 1,043), and group 4 (2011-2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period. © 2017 The Korean Academy of Medical Sciences.

  11. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice

    PubMed Central

    Carlström, Mattias; Larsen, Filip J.; Nyström, Thomas; Hezel, Michael; Borniquel, Sara; Weitzberg, Eddie; Lundberg, Jon O.

    2010-01-01

    The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate–nitrite–NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes. PMID:20876122

  12. Lowered circulating aspartate is a metabolic feature of human breast cancer

    PubMed Central

    Xie, Guoxiang; Zhou, Bingsen; Zhao, Aihua; Qiu, Yunping; Zhao, Xueqing; Garmire, Lana; Shvetsov, Yurii B.; Yu, Herbert; Yen, Yun; Jia, Wei

    2015-01-01

    Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer. PMID:26452258

  13. Nephrolithiasis in medullary sponge kidney: evaluation of clinical and metabolic features.

    PubMed

    McPhail, E Fred; Gettman, Matthew T; Patterson, David E; Rangel, Laureano J; Krambeck, Amy E

    2012-02-01

    Medullary sponge kidney (MSK) is a disorder characterized by tubular dilation of renal collecting ducts and cystic dilation of medullary pyramids that has been associated with stone disease. The significance of nephrolithiasis and the mechanisms by which it occurs are incompletely understood. We describe clinical and metabolic features of nephrolithiasis in a cohort of patients with MSK. Records were reviewed of 56 patients, all with radiographic diagnosis of medullary sponge kidney and data collected pertaining to presentation, stone events and recurrences, stone composition, and metabolic profile to perform a descriptive study with median 3.7 years follow-up. Nephrolithiasis was confirmed radiographically in 39/56 patients (69.6%). No patient without evidence of nephrolithiasis developed a stone event, whereas 13/39 (33%) of those with nephrolithiasis developed a recurrent stone event. Stones were composed of calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate apatite, and uric acid. Metabolic profile was obtained for 26 of 39 (67%) stone-forming patients demonstrating abnormalities in 22/26 (84.6%). These included hypercalciuria, 58% (15/26); low urine volume, 35% (9/26); hyperuricosuria, 27% (7/26); hypocitraturia, 19% (5/26); elevated urine sodium, 15% (4/26); and hyperoxaluria, 12% (3/26). Many patients with MSK have no evidence of nephrolithiasis. Among those who do, recurrence is common, and metabolic profile and composition are varied as in the general stone-forming population. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Lowered circulating aspartate is a metabolic feature of human breast cancer.

    PubMed

    Xie, Guoxiang; Zhou, Bingsen; Zhao, Aihua; Qiu, Yunping; Zhao, Xueqing; Garmire, Lana; Shvetsov, Yurii B; Yu, Herbert; Yen, Yun; Jia, Wei

    2015-10-20

    Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer.

  15. Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications

    PubMed Central

    Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry H.; Newburger, Jane W.; Kaza, Aditya K.; Franceschini, Maria A.; Kussman, Barry D.; Grant, P. Ellen

    2017-01-01

    The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management. PMID:28276534

  16. Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans

    PubMed Central

    Ibaraki, Masanobu; Shinohara, Yuki; Nakamura, Kazuhiro; Miura, Shuichi; Kinoshita, Fumiko; Kinoshita, Toshibumi

    2010-01-01

    Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with 15O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (CaO2), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO2 was independent of Hb concentration. Oxygen delivery defined as a product of CaO2 and CBF (CaO2 CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO2. The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the 15O PET data in clinical practice. PMID:20160738

  17. [Relationship between spot urine pH and number of metabolic syndrome features].

    PubMed

    Yamanishi, Hachiro

    2014-07-01

    A significant inverse relationship between the 24-hour urine pH and number of metabolic syndrome (MS) features(BMI ≥ 30 kg/m2, circumference > 88cm, HDL-cholesterol < 50mg/dL, etc.) was identified in individuals, which means that 24-hour urine pH values decrease with an increasing number of MS features. In this respect, we examined the association between the number of MS features and spot urine pH instead of 24-hour urine pH. A positive relationship was observed between the spot urine pH and number of MS features by analysis of covariance, with the age, gender, and eGFR as covariates. On the other hand, a high level of serum uric acid (UA) indicated a significantly lower spot urine pH compared with a normal level of UA. Serum UA was a significant independent variable explaining the decrease of the urine pH. The results of path analysis showed that UA had negative effects on the number of MS features and urine pH. Therefore, a positive relationship between the number of MS features and urine pH will be a spurious correlation with UA as a confounding factor. In addition, the negative relationship between the number of MS features and UA was also a spurious correlation with age as a confounding factor. From these results, the serum UA level should be considered to evaluate the relationship between the number of MS features and spot urine pH.

  18. Cerebral metabolic rate for glucose during the first six months of life: an FDG positron emission tomography study.

    PubMed Central

    Kinnala, A.; Suhonen-Polvi, H.; Aärimaa, T.; Kero, P.; Korvenranta, H.; Ruotsalainen, U.; Bergman, J.; Haaparanta, M.; Solin, O.; Nuutila, P.; Wegelius, U.

    1996-01-01

    AIM: To measure the local cerebral metabolic rate for glucose (LCMRGlc) in neonatal brains during maturation using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). METHODS: Twenty infants were studied using PET during the neonatal period. The postconceptional age ranged from 32.7 to 60.3 weeks. All infants had normal neurodevelopment and were normoglycaemic. The development of the infants was carefully evaluated (follow up 12-36 months) clinically, and by using a method based on Gesell Amatruda's developmental diagnosis. LCMRGlc was quantitated using PET derived from FDG kinetics and calculated in the whole brain and for regional brain structures. RESULTS: LCMRGlc for various cortical brain regions and the basal ganglia was low at birth (from 4 to 16 mumol/100 g/minute). In infants 2 months of age and younger LCMRGlc was highest in the sensorimotor cortex, thalamus, and brain stem. By 5 months, LCMRGlc had increased in the frontal, parietal, temporal, occipital and cerebellar cortical regions. In general, the whole brain LCMRGlc correlated with postconceptional age (r = 0.90; P < 0.001). The change in the glucose metabolic pattern observed in the neonatal brain reflects the functional maturation of these brain regions. CONCLUSION: These findings show that LCMRGlc in infants increases with maturation. Accordingly, when LCMRGlc is measured during infancy, the postconceptional age has to be taken into account when interpretating the results. Images Figure 1 PMID:8777676

  19. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers

    PubMed Central

    Kay, Daniel B.; Karim, Helmet T.; Soehner, Adriane M.; Hasler, Brant P.; Wilckens, Kristine A.; James, Jeffrey A.; Aizenstein, Howard J.; Price, Julie C.; Rosario, Bedda L.; Kupfer, David J.; Germain, Anne; Hall, Martica H.; Franzen, Peter L.; Nofzinger, Eric A.; Buysse, Daniel J.

    2016-01-01

    Study Objectives: The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Methods: Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21–60), sex, and race. We conducted [18F]fluoro-2-deoxy-d-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Results: Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected < 0.05. Conclusions: Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness. Citation: Kay DB, Karim HT, Soehner AM, Hasler BP, Wilckens KA, James JA, Aizenstein HJ, Price JC, Rosario BL, Kupfer DJ, Germain A, Hall MH, Franzen PL, Nofzinger EA, Buysse DJ. Sleep-wake differences in relative regional cerebral metabolic rate for glucose among

  20. Effects of Aging on Cerebral Blood Flow, Oxygen Metabolism, and Blood Oxygenation Level Dependent Responses to Visual Stimulation

    PubMed Central

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

    2010-01-01

    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% CO2) 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 (CMRO2) with activation, and the coupling ratio n of the fractional changes in CBF and CMRO2. 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 CMRO2 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. PMID:18465743

  1. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats

    PubMed Central

    Awwad, Hibah O.; Gonzalez, Larry P.; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J.; Awasthi, Vibhudutta; Standifer, Kelly M.

    2015-01-01

    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, 25,000–30,000 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 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 18F-fluorodeoxyglucose (18F-FDG). 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). PMID:26136722

  2. Blast Overpressure Waves Induce Transient Anxiety and Regional Changes in Cerebral Glucose Metabolism and Delayed Hyperarousal in Rats.

    PubMed

    Awwad, Hibah O; Gonzalez, Larry P; Tompkins, Paul; Lerner, Megan; Brackett, Daniel J; Awasthi, Vibhudutta; Standifer, Kelly M

    2015-01-01

    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, 25,000-30,000 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 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 (18)F-fluorodeoxyglucose ((18)F-FDG). 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).

  3. A network-based feature selection approach to identify metabolic signatures in disease.

    PubMed

    Netzer, Michael; Kugler, Karl G; Müller, Laurin A J; Weinberger, Klaus M; Graber, Armin; Baumgartner, Christian; Dehmer, Matthias

    2012-10-07

    The identification and interpretation of metabolic biomarkers is a challenging task. In this context, network-based approaches have become increasingly a key technology in systems biology allowing to capture complex interactions in biological systems. In this work, we introduce a novel network-based method to identify highly predictive biomarker candidates for disease. First, we infer two different types of networks: (i) correlation networks, and (ii) a new type of network called ratio networks. Based on these networks, we introduce scores to prioritize features using topological descriptors of the vertices. To evaluate our method we use an example dataset where quantitative targeted MS/MS analysis was applied to a total of 52 blood samples from 22 persons with obesity (BMI >30) and 30 healthy controls. Using our network-based feature selection approach we identified highly discriminating metabolites for obesity (F-score >0.85, accuracy >85%), some of which could be verified by the literature.

  4. A pilot study on metabolic syndrome and its associated features among Qatari schoolchildren

    PubMed Central

    Rizk, Nasser; Amin, Mona; Yousef, Mervat

    2011-01-01

    Aim: This pilot study aimed to evaluate the individual features of the metabolic syndrome (MeS) and its frequency in Qatari schoolchildren aged 6–12 years. Background: MeS has a strong future risk for development of diabetes and cardiovascular diseases. Childhood obesity is increasing the likelihood of MeS in children. Methods: The associated features of MeS were assessed in 67 children. They were recruited from the outpatient pediatric clinic at Hamad Medical Corporation, Qatar. Height, weight, and waist circumference were measured and body mass index was calculated for each child. Fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol and triglycerides (TG) were measured. MeS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-III) which was modified by Cook with adjustment for fasting glucose to ≥5.6 mM according to recommendations from the American Diabetes Association. Results: The overall prevalence of MeS according to NCEP-III criteria was 3.0% in children aged 6–12 years. Overweight and obesity was 31.3% in children aged 6–12 years, according to the International Obesity Task Force criteria. The prevalence of MeS was 9.5% in overweight and obese subjects. Increased TG levels represented the most frequent abnormality (28.4%) in metabolic syndrome features in all subjects, followed by HDL-C (19.4%) in all subjects. Conclusion: Increased TG levels and low HDL-C were the most frequent components of this syndrome. This study showed a significant prevalence of MeS and associated features among overweight and obese children. The overall prevalence of MeS in Qatari children is in accordance with data from several other countries. PMID:21845059

  5. Clinical features and the degree of cerebrovascular stenosis in different types and subtypes of cerebral watershed infarction.

    PubMed

    Li, Yue; Li, Man; Zhang, Xiaoyu; Yang, Shuna; Fan, Huimin; Qin, Wei; Yang, Lei; Yuan, Junliang; Hu, Wenli

    2017-08-29

    Whether there are differences in pathogenesis among different types and subtypes of cerebral watershed infarction (WSI) is controversial since they have been combined into a single group in most previous studies. We prospectively identified 340 supratentorial WSI patients at Beijing Chao-Yang Hospital, Capital Medical University, China and classified them based on diffusion-weighted imaging(DWI) templates. Baseline characteristics, clinical courses and neuroradiological features were compared among patients with different types and subtypes of WSI. We identified 92 patients with cortical watershed infarction (CWI), 112 with internal watershed infarction (IWI) and 136 with mixed-type infarction. Compared with CWI patients, more IWI patients had critical stenosis of internal carotid artery (ICA) (P < 0.001). For the CWI group, patients with anterior watershed infarction (AWI) were more prone to critical ICA stenosis than those with posterior watershed infarction (PWI) (P = 0.011). For the IWI group, critical ICA stenosis was more prevalent in patients with partial IWI (P-IWI) than in those with confluent IWI (C-IWI) (P = 0.026). IWI patients were more frequently found to have clinical deterioration during the first 7 days of hospitalization and a poor prognosis at the 90th day than in CWI patients (P = 0.003 and P = 0.014, respectively). IWI, especially the P-IWI subtype, is associated with hemodynamic impairment (HDI), whereas CWI has a weaker correlation with ICA steno-occlusion. Furthermore, IWI patients are more prone to poor prognosis.

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

    SciTech Connect

    Wu, J.C.; Hagman, J.; Buchsbaum, M.S.; Blinder, B.; Derrfler, M.; Tai, W.Y.; Hazlett, E.; Sicotte, N. )

    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.

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

    PubMed

    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 < .0055). The only significant intraoperative association found was increased deep hypothermic circulatory arrest time with reduced postoperative white matter glutamate and gamma-aminobutyric acid (P < .0072). Multiple postoperative factors, including increased number of extracorporeal membrane oxygenation days (P < .0067), intensive care unit, length of stay (P < .0047), seizures in the intensive care unit (P < .0009), and home antiepileptic use (P < .0002), were associated with reduced postoperative white matter n-acetyl aspartate. Multiple postoperative factors were found to be associated with altered brain metabolism in term infants with CHD, but not patient-specific, preoperative, or

  8. Circulatory and metabolic aspects of cerebral ischemia in experimental animals and in men.

    PubMed

    Fieschi, C; Battistini, N; Lenzi, G L

    1978-01-01

    In normal conditions, there is a precise link between regional metabolism and blood flow in the brain. In pathological states there may be an uncoupling between CBF and metabolism, due to many mechanisms. In particular, anaerobic glycolisis, membrane depolarization, and altered neurotransmitter release are relevant for the final damage of the tissue. Postischemic recovery was analyzed in experiments with 14C-deoxyglucose. In men, the noninvasive approach with 15O by inhalation allowed the determination of regional oxygen utilization. In TIAs, there is a chronic ischemic condition, while in strokes there is often a relative luxury perfusion.

  9. Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography

    SciTech Connect

    Tyler, J.L.; Strother, S.C.; Zatorre, R.J.; Alivisatos, B.; Worsley, K.J.; Diksic, M.; Yamamoto, Y.L.

    1988-05-01

    Cerebral glucose utilization (LCMRGI) was measured using the (/sup 18/F)fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values normalized by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical abnormal values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

  10. Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes.

    PubMed

    Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C

    2014-01-01

    Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications.

  11. Comparative genomics of three Methanocellales strains reveal novel taxonomic and metabolic features.

    PubMed

    Lyu, Zhe; Lu, Yahai

    2015-06-01

    Methanocellales represents a new order of methanogens, which is widespread in environments and plays specifically the important role in methane emissions from paddy fields. To gain more insights into Methanocellales, comparative genomic studies were performed among three Methanocellales strains through the same annotation pipeline. Genetic relationships among strains revealed by genome alignment, pan-genome reconstruction and comparison of amino average identity suggest that they should be classified in different genera. In addition, multiple copies of cell cycle regulator proteins were identified for the first time in Archaea. Core metabolisms were reconstructed, predicting certain unique and novel features for Methanocellales, including a set of methanogenesis genes potentially organized toward specialization in utilizing low concentrations of H2, a new route of disulfide reduction catalysed by a disulfide-reducing hydrogenase (Drh) complex phylogenetically related to sulfate-reducing prokaryotes, an oxidative tricarboxylic acid (TCA) cycle, a sophisticated nitrogen uptake and regulation system as well as a versatile sulfur utilization system. These core metabolisms are largely conserved among the three strains, but differences in gene copy number and metabolic diversity are evident. The present study thus adds new dimensions to the unique ecophysiology of Methanocellales and offers a road map for further experimental characterization of this methanogen lineage.

  12. Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression: a randomized, placebo-controlled study.

    PubMed

    Smith, Gwenn S; Reynolds, Charles F; Houck, Patricia R; Dew, Mary Amanda; Ginsberg, Joshua; Ma, Yilong; Mulsant, Benoit H; Pollock, Bruce G

    2009-01-30

    A randomized, placebo-controlled study was performed to evaluate whether the onset of the glucose metabolic effects of a selective serotonin reuptake inhibitor (paroxetine) would be accelerated by total sleep deprivation (TSD). Patients were randomly assigned to one of three groups: TSD and paroxetine treatment, TSD and 2 weeks of placebo followed by paroxetine treatment, or 2 weeks of paroxetine treatment. Sixteen elderly depressed patients who met DSM-IV criteria for major depressive disorder and nine age-matched comparison subjects underwent positron emission tomography (PET) studies of cerebral glucose metabolism at baseline, post-TSD (or a normal night's sleep for the paroxetine- only group), post-recovery sleep and 2 weeks post-paroxetine or placebo treatment (patients only). TSD was not consistently associated with a decrease in depressive symptoms between groups nor with decreases in cerebral metabolism in cortical regions that have been associated with rapid and sustained clinical improvement (e.g. anterior cingulate gyrus). The observation of a synergistic antidepressant effect of combined TSD and paroxetine treatment that was observed in a previous "open label" pilot study was not observed in the present randomized study, consistent with lack of a cerebral metabolic effect in brains regions previously shown to be associated with improvement of depressive symptoms.

  13. The Cerebral Glucose Metabolic Response to Combined Total Sleep Deprivation and Antidepressant Treatment in Geriatric Depression: A Randomized, Placebo Controlled Study

    PubMed Central

    Smith, Gwenn S.; Reynolds, Charles F.; Houck, Patricia R.; Dew, Mary Amanda; Ginsberg, Joshua; Ma, Yilong; Mulsant, Benoit H.; Pollock, Bruce G.

    2009-01-01

    A randomized, placebo controlled study was performed to evaluate whether the onset of the glucose metabolic effects of a selective serotonin reuptake inhibitor (paroxetine) would be accelerated by total sleep deprivation (TSD). Patients were randomly assigned to one of three groups: TSD and paroxetine treatment, TSD and two weeks of placebo followed by paroxetine treatment, or two weeks of paroxetine treatment. Sixteen elderly depressed patients who met DSM-IV criteria for major depressive disorder and nine age-matched comparison subjects underwent Positron Emission Tomography (PET) studies of cerebral glucose metabolism at baseline, post-TSD (or a normal night’s sleep for the paroxetine only group), post-recovery sleep and two weeks post-paroxetine or placebo treatment (patients only). TSD was not consistently associated with a decrease in depressive symptoms between groups nor with decreases in cerebral metabolism in cortical regions that have been associated with rapid and sustained clinical improvement (e.g. anterior cingulate gyrus). The observation of a synergistic antidepressant effect of combined TSD and paroxetine treatment that was observed in a previous “open label”, pilot study was not observed in the present randomized study, consistent with lack of a cerebral metabolic effect in brains regions previously shown to be associated with improvement of depressive symptoms. PMID:19087899

  14. Eszopiclone and Dexmedetomidine Depress Ventilation in Obese Rats with Features of Metabolic Syndrome

    PubMed Central

    Filbey, William A.; Sanford, David T.; Baghdoyan, Helen A.; Koch, Lauren G.; Britton, Steven L.; Lydic, Ralph

    2014-01-01

    Study Objectives: Obesity alters the therapeutic window of sedative/hypnotic drugs and increases the probability of respiratory complications. The current experiments used an established rodent model of obesity to test the hypothesis that the sedative/hypnotic drugs eszopiclone and dexmedetomidine alter ventilation differentially in obese rats compared with lean/fit rats. Design: This study used a within-groups/between-groups experimental design. Setting: University of Michigan. Participants: Experiments were conducted using lean/fit rats (n = 21) and obese rats (n = 21) that have features of metabolic syndrome. Interventions: Breathing was measured with whole-body plethysmography after systemic administration of vehicle (control), the nonbenzodiazepine, benzodiazepine site agonist eszopiclone, or the alpha-2 adrenergic receptor agonist dexmedetomidine. Measurements and Results: Data were analyzed using two-way analysis of variance and appropriate post hoc comparisons. At baseline, the obese/metabolic syndrome rats had increased respiratory rates (21.6%), lower tidal volumes/body weight (-24.1%), and no differences in minute ventilation compared to lean/fit rats. In the obese rats, respiratory rate was decreased by dexmedetomidine (-29%), but not eszopiclone. In the lean and the obese rats, eszopiclone decreased tidal volume (-12%). Both sedative/hypnotic drugs caused a greater decrease in minute ventilation in the obese (-26.3%) than lean (-18%) rats. Inspiratory flow rate (VT / TI) of the obese rats was decreased by dexmedetomidine (-10.6%) and eszopiclone (-18%). Duty cycle (TI / TTOT) in both rat lines was decreased by dexmedetomidine (-16.5%) but not by eszopiclone. Conclusions: Dexmedetomidine, in contrast to eszopiclone, decreased minute ventilation in the obese/metabolic syndrome rats by depressing both duty cycle and inspiratory flow rate. The results show for the first time that the obese phenotype differentially modulates the respiratory effects of

  15. Caffeine induced uncoupling of cerebral blood flow and oxygen metabolism: A calibrated-BOLD fMRI study

    PubMed Central

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2009-01-01

    Although functional MRI (fMRI) based on blood oxygenation-level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia calibrated-BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). In this study, we implemented a quantitative R2* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated-BOLD method, to examine the CBF and CMRO2 responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200mg caffeine dose. A dual echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, ±11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, ±2.9) and CMRO2 (+20.7%, ±1.4), and caffeine decreased CBF (-34.5%, ±2.6) with a non-significant change in CMRO2 (+5.2%, ±6.4). The coupling between CBF and CMRO2 was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated-BOLD methodology using R2* is a promising approach for evaluating CBF and CMRO2 changes in response to pharmacological interventions. PMID:18191583

  16. Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study.

    PubMed

    Perthen, Joanna E; Lansing, Amy E; Liau, Joy; Liu, Thomas T; Buxton, Richard B

    2008-03-01

    Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.

  17. High temporal resolution MRI quantification of global cerebral metabolic rate of oxygen consumption in response to apneic challenge.

    PubMed

    Rodgers, Zachary B; Jain, Varsha; Englund, Erin K; Langham, Michael C; Wehrli, Felix W

    2013-10-01

    We present a technique for quantifying global cerebral metabolic rate of oxygen consumption (CMRO2) in absolute physiologic units at 3-second temporal resolution and apply the technique to quantify the dynamic CMRO2 response to volitional apnea. Temporal resolution of 3 seconds was achieved via a combination of view sharing and superior sagittal sinus-based estimation of total cerebral blood flow (tCBF) rather than tCBF measurement in the neck arteries. These modifications were first validated in three healthy adults and demonstrated to produce minimal errors in image-derived blood flow and venous oxygen saturation (SvO2) values. The technique was then applied in 10 healthy adults during an apnea paradigm of three repeated 30-second breath-holds. Subject-averaged baseline tCBF, arteriovenous oxygen difference (AVO2D), and CMRO2 were 48.6 ± 7.0 mL/100 g per minute, 29.4 ± 3.4 %HbO2, and 125.1 ± 11.4 μmol/100 g per minute, respectively. Subject-averaged maximum changes in tCBF and AVO2D were 43.5 ± 9.4% and -32.1 ± 5.7%, respectively, resulting in a small (6.0 ± 3.5%) but statistically significant (P=0.00044, two-tailed t-test) increase in average end-apneic CMRO2. This method could be used to investigate neurometabolic-hemodynamic relationships in normal physiology, to better define the biophysical origins of the BOLD signal, and to quantify neurometabolic responsiveness in diseases of altered neurovascular reactivity.

  18. Dysmorphic features, frontal cerebral cavernoma and hyperglycemia in a girl with a de novo deletion of 7.23 Mb in region 7p13-p12.1.

    PubMed

    López, Gilberto Pérez; Quispe, Beatriz Villafuerte; Cabrejas Núñez, María José; Castaño, Luis; Barrio, Raquel

    2017-04-07

    We describe the case of a 7 year old girl referred to our Diabetes Unit for hyperglycemia associated to facial dysmorphic features, intellectual disability and cerebral cavernomas, who was initially diagnosed with type 1 diabetes mellitus (positive anti-IA2 antibody and HLA DR3/DR4/DQ2). In follow up, due to the evolution of the diabetes (very good metabolic control with low insulin dose and negative IA-2 antibodies - samples analyzed in two different laboratories-), first clinical suspicion was GCK-related Maturity-Onset Diabetes of the Young (MODY 2) by persistent mild hyperglycemia in the fasting state, which was substantiated in Multiplex Ligation-dependent Probe Amplification (MLPA). MLPA showed a heterozygous GCK deletion (exons 1 to 12). However, her parents did not have such deletion and were clinically euglycemic. Given the clinical picture and the MLPA findings, array-CGH was performed showing a monoallelic deletion of 7.23Mb in the short arm of chromosome 7 (7p13p12.1). The deleted intervalis contain 39 genes listed in OMIM list, including: GCK associated with MODY 2, CCM2 associated with type 2 cerebral cavernous malformations, IGFBP-3 associated with decreased in postnatal growth and OGDH: associated with alpha-ketoglutarate dehydrogenase deficiency (cognitive impairment and movement abnormalities). This previously unreported deletion explains the clinical picture of the patient and suggests that 7p13p12.1 contains genes involved in intellectual disability and craniofacial development.

  19. Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.

    PubMed

    Buchsbaum, M S; Hollander, E; Haznedar, M M; Tang, C; Spiegel-Cohen, J; Wei, T C; Solimando, A; Buchsbaum, B R; Robins, D; Bienstock, C; Cartwright, C; Mosovich, S

    2001-06-01

    The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.

  20. Intelligence and Changes in Regional Cerebral Glucose Metabolic Rate Following Learning.

    ERIC Educational Resources Information Center

    Haier, Richard J.; And Others

    1992-01-01

    A study of eight normal right-handed men demonstrates widespread significant decreases in brain glucose metabolic rate (GMR) following learning a complex computer task, a computer game. Correlations between magnitude of GMR change and intelligence scores are also demonstrated. (SLD)

  1. Intelligence and Changes in Regional Cerebral Glucose Metabolic Rate Following Learning.

    ERIC Educational Resources Information Center

    Haier, Richard J.; And Others

    1992-01-01

    A study of eight normal right-handed men demonstrates widespread significant decreases in brain glucose metabolic rate (GMR) following learning a complex computer task, a computer game. Correlations between magnitude of GMR change and intelligence scores are also demonstrated. (SLD)

  2. Muscle energy metabolism: structural and functional features in different types of porcine striated muscles.

    PubMed

    Huber, Korinna; Petzold, Johanna; Rehfeldt, Charlotte; Ender, Klaus; Fiedler, Ilse

    2007-01-01

    Striated muscles exhibit a wide range of metabolic activity levels. Heart and diaphragm are muscles with continuous contractile performance, which requires life-long function. In contrast, skeletal muscles like longissimus muscle can adapt metabolism from resting to different stages of exercise. The aim of this study was to compare the morphological features of these three muscles and the expression of genes that are important for energy metabolism. Therefore, histochemical studies were performed for determination of muscle fibre type composition. Oxidative and glycolytic capacity was assessed by measuring isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH) activities. The mRNA expression of glucose transporter 4 (GLUT 4), growth hormone receptor (GHR) and AMP-activated kinase (AMPK) alpha(1) and alpha(2) subunits was studied by semiquantitative Northern blotting. Heart, and to a slightly lesser extent diaphragm were highly oxidative muscles characterised by high expression of oxidative muscle fibres and ICDH activity. Longissimus muscle exhibited the highest percentage of glycolytic fibres and LDH activity. GLUT 4 mRNA was lowest in heart reflecting the dependency of heart muscle on fatty acids as major energy source. Higher expression of GLUT 4 in diaphragm indicated that glucose is an important energy substrate in this oxidative muscle. Highest GLUT 4 expression in longissimus should be essential for the refilling of glycogen stores after exercise. AMPK subunits, which are important stimulators of GLUT 4 protein insertion into the sarcolemma, are also highest expressed in longissimus muscle indicating the strong capacity to adapt energy metabolism to large changes in energy demand. Interestingly, AMPK alpha(1) subunit expression on protein level is strongly restricted to muscle fibres containing type I myosin in this muscle. GHR mRNA expression was also highest in longissimus muscle indicating that an enhanced effect of growth hormone, which is

  3. Cerebral toxoplasmosis in HIV-positive patients in Brazil: clinical features and predictors of treatment response in the HAART era.

    PubMed

    Vidal, José E; Hernandez, Adrian V; de Oliveira, Augusto C Penalva; Dauar, Rafi F; Barbosa, Silas Pereira; Focaccia, Roberto

    2005-10-01

    A prospective study of 55 confirmed or presumptive cases of cerebral toxoplasmosis in HIV positive patients in Brazil was performed to describe clinical characteristics and to identify predictive factors for clinical response to the anti-Toxoplasma treatment. Cerebral toxoplasmosis led to the diagnosis of HIV infection in 19 (35%) patients, whereas it was the AIDS defining disease in 41 (75%) patients. Of these, 22 (54%) patients were previously know to be HIV-positive. At diagnosis of cerebral toxoplasmosis, only 4 (7%) patients were on highly active antiretroviral therapy (HAART), and 6 (11%) were receiving primary cerebral toxoplasmosis prophylaxis. The mean CD4+ cell count was 64.2 (+/- 69.1) cells per microliter. Forty-nine patients (78%) showed alterations consistent with toxoplasmosis on brain computed tomography. At 6 weeks of treatment, 23 (42%) patients had complete clinical response, 25 (46%) partial response, and 7 (13%) died. Alteration of consciousness, Karnofsky score less than 70, psychomotor slowing, hemoglobin less than 12 mg/dL, mental confusion, Glasgow Coma Scale less than 12 were the main predictors of partial clinical response. All patients were placed on HAART within the first 4 weeks of diagnosis of cerebral toxoplasmosis. One year after the diagnosis, all available patients were on HAART and toxoplasmosis prophylaxis, and only 2 patients had relapse of cerebral toxoplasmosis. In Brazilian patients with AIDS, cerebral toxoplasmosis mainly occurs as an AIDS-defining disease, and causes significant morbidity and mortality. Signs of neurologic deterioration predict an unfavorable response to the treatment. Early start of HAART seems to be related to better survival and less relapses.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  6. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

    PubMed

    Volek, Jeff S; Feinman, Richard D

    2005-11-16

    surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  7. 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.

    PubMed

    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.

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

    PubMed

    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.

  9. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    SciTech Connect

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-06-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of /sup 18/F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.

  10. Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a micro-PET study.

    PubMed

    Idbaih, Ahmed; Burlet, Arlette; Adle-Biassette, Homa; Boisgard, Raphaël; Coulon, Christine; Paris, Sophie; Marie, Yannick; Donadieu, Jean; Hoang-Xuan, Khê; Ribeiro, Maria-Joao

    2007-07-16

    The Brattleboro rat is an animal model of genetically induced central diabetes insipidus. These rats show cognitive and behavioral disorders, but no neurodegenerative disease has been observed. We studied brain glucose uptake, a marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats was studied in vivo and another group of animals was studied ex vivo. In vivo studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F-FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F-FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo (p<0.05), but only a trend towards higher values was found ex vivo. Our results show for the first time that brain glucose metabolism is modified in Brattleboro rats. This altered brain glucose metabolism in Brattleboro rats may be related to the observed cognitive and behavioral disorders. Functional analyses of brain metabolism are promising to investigate cognitive behavioral disturbances observed in Brattleboro rats and their link to diabetes insipidus.

  11. Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral metabolic rate.

    PubMed

    Buchsbaum, Monte S; Shihabuddin, Lina; Hazlett, Erin A; Schröder, Johannes; Haznedar, Mehmet M; Powchik, Peter; Spiegel-Cohen, Jacqueline; Wei, Tsechung; Singer, Melissa B; Davis, Kenneth L

    2002-05-01

    We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10) characterized by an unremitting and severe course and the non-Kraepelinian subtype (n = 17) characterized by a remitting course and some periods of self-care. Patients were assessed with positron emission tomography (PET) with 18F-deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI). A group of 32 age- and sex-matched normal volunteers served as comparison subjects. During the FDG tracer uptake period, patients performed a serial verbal learning task. MR images were segmented into gray, white and cerebrospinal fluid regions, and warped to average normal coordinates. PET images were coregistered to the MR images and similarly warpedfor analysis. Kraepelinian subtype patients were characterized by lower metabolic rates in the temporal lobe and cingulategyrus. and lower fronto/occipital ratios than non-Kraepelinian subtype patients. Exploratory statistical probability mapping alsorevealed lower metabolic rates in the right striatum in Kraepelinian versus non-Kraepelinian patients. These differences couldnot be attributed to differences in age, symptom severity, task performance during FDG uptake, or severity of involuntary movements. Factor analysis of the cortical surface identified significantly lower temporal lobe metabolic rates in Kraepelinian patients than non-Kraepelinian patients. A combined frontal/temporal deficit or greater cortical change may be associated with poorer longitudinal course.

  12. Targeting glutamine metabolism rescues mice from late-stage cerebral malaria.

    PubMed

    Gordon, Emile B; Hart, Geoffrey T; Tran, Tuan M; Waisberg, Michael; Akkaya, Munir; Kim, Ann S; Hamilton, Sara E; Pena, Mirna; Yazew, Takele; Qi, Chen-Feng; Lee, Chen-Fang; Lo, Ying-Chun; Miller, Louis H; Powell, Jonathan D; Pierce, Susan K

    2015-10-20

    The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15-25% in African children despite effective antimalarial chemotherapy. There are no adjunctive treatments for CM, so there is an urgent need to identify new targets for therapy. Here we show that the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) rescues mice from CM when administered late in the infection a time at which mice already are suffering blood-brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by accumulation of parasite-specific CD8(+) effector T cells and infected red blood cells in the brain. Remarkably, within hours of DON treatment mice showed blood-brain barrier integrity, reduced brain swelling, decreased function of activated effector CD8(+) T cells in the brain, and levels of brain metabolites that resembled those in uninfected mice. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children.

  13. Sleep-Wake Differences in Relative Regional Cerebral Metabolic Rate for Glucose among Patients with Insomnia Compared with Good Sleepers.

    PubMed

    Kay, Daniel B; Karim, Helmet T; Soehner, Adriane M; Hasler, Brant P; Wilckens, Kristine A; James, Jeffrey A; Aizenstein, Howard J; Price, Julie C; Rosario, Bedda L; Kupfer, David J; Germain, Anne; Hall, Martica H; Franzen, Peter L; Nofzinger, Eric A; Buysse, Daniel J

    2016-10-01

    The neurobiological mechanisms of insomnia may involve altered patterns of activation across sleep-wake states in brain regions associated with cognition, self-referential processes, affect, and sleep-wake promotion. The objective of this study was to compare relative regional cerebral metabolic rate for glucose (rCMRglc) in these brain regions across wake and nonrapid eye movement (NREM) sleep states in patients with primary insomnia (PI) and good sleeper controls (GS). Participants included 44 PI and 40 GS matched for age (mean = 37 y old, range 21-60), sex, and race. We conducted [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography scans in PI and GS during both morning wakefulness and NREM sleep at night. Repeated measures analysis of variance was used to test for group (PI vs. GS) by state (wake vs. NREM sleep) interactions in relative rCMRglc. Significant group-by-state interactions in relative rCMRglc were found in the precuneus/posterior cingulate cortex, left middle frontal gyrus, left inferior/superior parietal lobules, left lingual/fusiform/occipital gyri, and right lingual gyrus. All clusters were significant at Pcorrected < 0.05. Insomnia was characterized by regional alterations in relative glucose metabolism across NREM sleep and wakefulness. Significant group-by-state interactions in relative rCMRglc suggest that insomnia is associated with impaired disengagement of brain regions involved in cognition (left frontoparietal), self-referential processes (precuneus/posterior cingulate), and affect (left middle frontal, fusiform/lingual gyri) during NREM sleep, or alternatively, to impaired engagement of these regions during wakefulness.

  14. Correlation Between Cerebral Atrophy and Texture Features in Alzheimer-type Dementia Brains: A 3-Year Follow-up MRI Study

    NASA Astrophysics Data System (ADS)

    Kodama, Naoki; Takeuchi, Hiroshi

    We assessed relationships between six texture features and changes in atrophy of the cerebral parenchyma, the hippocampus, and the parahippocampal gyrus in the Alzheimer-type dementia (ATD) brain to determine whether or not the features reflect cerebral atrophy in ATD patients. The subjects of this study were 10 ATD patients, and underwent an magnetic resonanse imaging test of the head annually for at least 3 consecutive years. They consisted of three men and seven women, with a mean age of 71.4 ± 6.7 years. The results of study, the mean run length nonuniformity (RLN), angular second moment (ASM), and contrast (CON) increased with time, whereas the mean gray level nonuniformity (GLN), run percentage (RPC), and entropy (ENT) decreased with time. There was a statistically significant correlation between brain-intracranial area ratio (BIR) and GLN (p = 0.039), between BIR and ASM (p = 0.011), and between BIR and ENT (p = 0.023) as well as between parahippocampal-intracranial area ratio and GLN (p = 0.049). These results indicate that the six texture features were shown to reflect gray matter atrophy associated with ATD and to change with the progress of the disease. Although the course of ATD can be followed up by measuring a hippocampal area or volume and determining a decrease in the area or volume, texture features should be a more effective instrument for identifying the progress of ATD.

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

    PubMed

    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.

  16. Invariant features of metabolic networks: a data analysis application on scaling properties of biochemical pathways

    NASA Astrophysics Data System (ADS)

    Giuliani, Alessandro; Zbilut, Joseph P.; Conti, Filippo; Manetti, Cesare; Miccheli, Alfredo

    2004-06-01

    The network metaphor is currently one of the most common general paradigms in biological sciences: this paradigm spans different scales of definition going from gene regulation to protein-protein interaction studies and metabolic regulation networks. Generally, the networks are defined by the nature of the connected elements (nodes) and their relative relations (edges). In this paper we demonstrate how the same biochemical regulation network can assume different shapes in terms of both constituting elements and intervening relations while remaining recognizable as a specific entity. This behaviour can be explained by the general scaling properties of biological networks and points to regulation pathways as emergent features of biochemical systems posited at a different hierarchical level with respect to the intervening metabolites.

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

    PubMed

    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.

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

    PubMed

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

    2017-04-21

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

  19. [Effect of disulfiram on energy metabolism (redox potential shift) coupled to paradoxical sleep episodes in rat cerebral cortex].

    PubMed

    Shvets-Ténéta-Guriĭ, T B; Dubinin, A G; Troshin, G I

    2012-01-01

    Disulfiram (DS) is widely used to treat patients with chronic alcoholism. DS treatment multiplies PS episodes. In this work, DS effect on the number of PS episodes and on the energy metabolism changes in the cerebral cortex (coupled to PS episodes) was investigated for the first time in rats. Polygraphic recording of the redox potential E (with platinum electrodes implanted in several cortical sites), electrocorticogram, neck electromyogram, and general motor activity were made in sleep-wake cycles. Rats received DS (100 mg/kg) with meals for two nights, after which the number of PS episodes increased almost twice during two subsequent sessions (prior to receiving DS). This was evidence of an increase in PS pressure coupled to a decrease of norepinephrine level in the brain. DS also evoked sharp decrease in the amount of the positive E shifts related to PS, which were replaced by the negative E shifts or by the two-phase E shifts (negative-positive waves). The absolute mean amplitude decreased both for the positive E shifts and the negative E shifts. These findings demonstrate prevailing glycolytic compartment as a source of fuel supporting PS and the inhibition in all brain energetic compartments. The data presented well agree with the conception that glycolysis becomes the main source for the brain activity under pathology conditions.

  20. Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (/sup 18/F)fluorodeoxyglucose

    SciTech Connect

    Friedland, R.P.; Budinger, T.F.; Ganz, E.; Yano, Y.; Mathis, C.A.; Koss, B.; Ober, B.A.; Huesman, R.H.; Derenzo, S.E.

    1983-08-01

    Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using (/sup 18/F)fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in all the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.

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

    SciTech Connect

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

    1988-05-01

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

  2. Motor- and food-related metabolic cerebral changes in the activity-based rat model for anorexia nervosa: a voxel-based microPET study.

    PubMed

    van Kuyck, Kris; Casteels, Cindy; Vermaelen, Peter; Bormans, Guy; Nuttin, Bart; Van Laere, Koen

    2007-03-01

    Anorexia nervosa (AN) is a disorder that is difficult to treat with psycho- or pharmacotherapy. In order to identify involved neurocircuitry, we investigated the cerebral metabolic alterations in the activity-based anorexia (ABA) rat model, where restriction of the food intake period induces hyperactivity and decreased body weight. Cerebral (18)F-fluorodeoxyglucose uptake was investigated in rats in the activity-based anorexia model (n=9) and compared to controls (n=10), using a CTI Focus microPET 220. Regional metabolic changes were investigated using statistical parametric mapping (SPM2) and correlated to weight and hyperactivity measures on a voxel-by-voxel basis. Higher regional metabolism was found in ABA rats in the mediodorsal thalamus, ventral pontine nuclei and cerebellum, while hypometabolism was seen in the left rhinal and bilateral insular cortex, and bilateral ventral striatum (p<0.001). A positive correlation was observed between body weight loss and brain metabolism in the cingulate cortex and surrounding motor and somatosensory cortex (p<0.001). Thus, in the ABA model metabolic changes are present in brain areas related to disease status and weight loss, which share several characteristics with the human disease.

  3. Meglumine Exerts Protective Effects against Features of Metabolic Syndrome and Type II Diabetes

    PubMed Central

    Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C.

    2014-01-01

    Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications. PMID:24587200

  4. Reproductive and metabolic features during puberty in sons of women with polycystic ovary syndrome.

    PubMed

    Crisosto, Nicolas; Echiburú, Barbara; Maliqueo, Manuel; Luchsinger, Marta; Rojas, Pedro; Recabarren, Sergio; Sir-Petermann, Teresa

    2017-09-14

    Intrauterine life may be implicated in the origin of polycystic cvary syndrome (PCOS) modifying the endocrine and metabolic function of children born to PCOS mothers independently of the genetic inheritance and gender. The aim of the present study was to evaluate the reproductive and metabolic function in sons of women with PCOS during puberty. Sixty nine PCOSs and 84 control sons (Cs) 7 to 18 years old matched by Tanner stage score were studied. A complete physical examination was conducted including anthropometric measurements (weight, height, waist, hip, body mass index (BMI)). An oral glucose tolerance test was performed and circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), testosterone (T), androstenedione (A4), 17 α-hydroxyprogesterone (17-OHP) and AMH were determined in the fasting sample. Waist to hip ratio (WHR), FSH and androstenedione levels were significantly higher in the PCOSs group compared to control boys during Tanner stage II-III. In Tanner stages II-III and IV-V PCOSs showed significantly higher total cholesterol and LDL levels. Propensity score analysis showed that higher LDL levels were attributable to the PCOSs condition and not to other metabolic factors. AMH levels were comparable during all stages. The rest of the parameters were comparable between both groups. Sons of women with PCOS show increased total cholesterol and LDL levels during puberty, which may represent latent insulin resistance. Thus, this is a group that should be followed and studied looking for further features of insulin resistance and cardiovascular risk markers. Reproductive markers on the other hand are very similar to controls.

  5. Endocrino-metabolic features in women with polycystic ovary syndrome during pregnancy.

    PubMed

    Paradisi, G; Fulghesu, A M; Ferrazzani, S; Moretti, S; Proto, C; Soranna, L; Caruso, A; Lanzone, A

    1998-03-01

    To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.

  6. Probing genetic algorithms for feature selection in comprehensive metabolic profiling approach.

    PubMed

    Zou, Wei; Tolstikov, Vladimir V

    2008-04-01

    Six different clones of 1-year-old loblolly pine (Pinus taeda L.) seedlings grown under standardized conditions in a green house were used for sample preparation and further analysis. Three independent and complementary analytical techniques for metabolic profiling were applied in the present study: hydrophilic interaction chromatography (HILIC-LC/ESI-MS), reversed-phase liquid chromatography (RP-LC/ESI-MS), and gas chromatography all coupled to mass spectrometry (GC/TOF-MS). Unsupervised methods, such as principle component analysis (PCA) and clustering, and supervised methods, such as classification, were used for data mining. Genetic algorithms (GA), a multivariate approach, was probed for selection of the smallest subsets of potentially discriminative classifiers. From more than 2000 peaks found in total, small subsets were selected by GA as highly potential classifiers allowing discrimination among six investigated genotypes. Annotated GC/TOF-MS data allowed the generation of a small subset of identified metabolites. LC/ESI-MS data and small subsets require further annotation. The present study demonstrated that combination of comprehensive metabolic profiling and advanced data mining techniques provides a powerful metabolomic approach for biomarker discovery among small molecules. Utilizing GA for feature selection allowed the generation of small subsets of potent classifiers.

  7. The genome of Pelobacter carbinolicus reveals surprising metabolic capabilities and physiological features

    SciTech Connect

    Aklujkar, Muktak; Haveman, Shelley; DiDonatoJr, Raymond; Chertkov, Olga; Han, Cliff; Land, Miriam L; Brown, Peter; Lovley, Derek

    2012-01-01

    Background: The bacterium Pelobacter carbinolicus is able to grow by fermentation, syntrophic hydrogen/formate transfer, or electron transfer to sulfur from short-chain alcohols, hydrogen or formate; it does not oxidize acetate and is not known to ferment any sugars or grow autotrophically. The genome of P. carbinolicus was sequenced in order to understand its metabolic capabilities and physiological features in comparison with its relatives, acetate-oxidizing Geobacter species. Results: Pathways were predicted for catabolism of known substrates: 2,3-butanediol, acetoin, glycerol, 1,2-ethanediol, ethanolamine, choline and ethanol. Multiple isozymes of 2,3-butanediol dehydrogenase, ATP synthase and [FeFe]-hydrogenase were differentiated and assigned roles according to their structural properties and genomic contexts. The absence of asparagine synthetase and the presence of a mutant tRNA for asparagine encoded among RNA-active enzymes suggest that P. carbinolicus may make asparaginyl-tRNA in a novel way. Catabolic glutamate dehydrogenases were discovered, implying that the tricarboxylic acid (TCA) cycle can function catabolically. A phosphotransferase system for uptake of sugars was discovered, along with enzymes that function in 2,3-butanediol production. Pyruvate: ferredoxin/flavodoxin oxidoreductase was identified as a potential bottleneck in both the supply of oxaloacetate for oxidation of acetate by the TCA cycle and the connection of glycolysis to production of ethanol. The P. carbinolicus genome was found to encode autotransporters and various appendages, including three proteins with similarity to the geopilin of electroconductive nanowires. Conclusions: Several surprising metabolic capabilities and physiological features were predicted from the genome of P. carbinolicus, suggesting that it is more versatile than anticipated.

  8. The genome of Pelobacter carbinolicus reveals surprising metabolic capabilities and physiological features

    PubMed Central

    2012-01-01

    Background The bacterium Pelobacter carbinolicus is able to grow by fermentation, syntrophic hydrogen/formate transfer, or electron transfer to sulfur from short-chain alcohols, hydrogen or formate; it does not oxidize acetate and is not known to ferment any sugars or grow autotrophically. The genome of P. carbinolicus was sequenced in order to understand its metabolic capabilities and physiological features in comparison with its relatives, acetate-oxidizing Geobacter species. Results Pathways were predicted for catabolism of known substrates: 2,3-butanediol, acetoin, glycerol, 1,2-ethanediol, ethanolamine, choline and ethanol. Multiple isozymes of 2,3-butanediol dehydrogenase, ATP synthase and [FeFe]-hydrogenase were differentiated and assigned roles according to their structural properties and genomic contexts. The absence of asparagine synthetase and the presence of a mutant tRNA for asparagine encoded among RNA-active enzymes suggest that P. carbinolicus may make asparaginyl-tRNA in a novel way. Catabolic glutamate dehydrogenases were discovered, implying that the tricarboxylic acid (TCA) cycle can function catabolically. A phosphotransferase system for uptake of sugars was discovered, along with enzymes that function in 2,3-butanediol production. Pyruvate:ferredoxin/flavodoxin oxidoreductase was identified as a potential bottleneck in both the supply of oxaloacetate for oxidation of acetate by the TCA cycle and the connection of glycolysis to production of ethanol. The P. carbinolicus genome was found to encode autotransporters and various appendages, including three proteins with similarity to the geopilin of electroconductive nanowires. Conclusions Several surprising metabolic capabilities and physiological features were predicted from the genome of P. carbinolicus, suggesting that it is more versatile than anticipated. PMID:23227809

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

    PubMed Central

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

    2015-01-01

    Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

  10. Application of the ''bootstrap'' technique to understanding cerebral interregional metabolic relationships

    SciTech Connect

    Metter, E.J.; Riege, W.H.; Kuhl, D.E.; Phelps, M.E.

    1984-01-01

    The authors' previous studies using (F18)-flourodeoxyglucose with positron computed tomography examined region to region metabolic correlations in (1) normal subjects, (2) normal elderly versus younger individuals, and (3) Alzheimer's, Huntington's and Parkinson's Diseases. Variations in the correlation matrices suggested differences in how brain regions function together. An alternative explanation was that the distribution of each matrix was not distinctly different, and the observations represented variations from the same distribution. To examine this tissue, the authors focused on the observation of differences in the total number of reliable correlations (i.e. correlations with r representing a p .01 uncorrected for the number of correlations) between the groups. For example in Parkinson Disease a total of 12 reliable correlations were found, as compared to 34 in Alzheimer's Disease. Four groups were compared including normal elderly, normal young, Alzheimer and Parkinson's Diseases. For each group, random samples were drawn from the studied subjects, and correlation matrices were calculated from the new samples. 508 matrices were calculated for the two normal groups, and 1016 were calculated for the Alzheimer's and Parkinson's groups. The total number of reliable correlations were counted for each matrix and the distribution of these counts were examined. Distinct differences were found in the mean, median and mode for each group. In particular, Parkinson's Disease peaked the earliest of the four groups, while Alzheimer's peaked the latest. The findings demonstrated that the metabolic data for each group were derived from different populations.

  11. Cerebral energy metabolism and the brain's functional network architecture: an integrative review

    PubMed Central

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's ‘functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks. PMID:23756687

  12. Preoperative differences of cerebral metabolism relate to the outcome of cochlear implants in congenitally deaf children.

    PubMed

    Lee, Hyo Jeong; Kang, Eunjoo; Oh, Seung-Ha; Kang, Hyejin; Lee, Dong Soo; Lee, Myung Chul; Kim, Chong-Sun

    2005-05-01

    In congenitally deaf children, chronological age is generally accepted as a critical factor that affects successful rehabilitation following cochlear implantation (CI). However, a wide variance among patients is known to exist regardless of the age at CI [Sarant, J.Z., Blamey, P.J., Dowell, R.C., Clark, G.M., Gibson, W.P., 2001. Variation in speech perception scores among children with cochlear implants. Ear Hear. 22, 18-28]. In a previous study, we reported that prelingually deaf children in the age range 5-7 years at implantation showed greatest outcome variability [Oh S.H., Kim C.S., Kang E.J., Lee D.S., Lee H.J., Chang S.O., Ahn S.H., Hwang C.H., Park H.J., Koo J.W., 2003. Speech perception after cochlear implantation over a 4-year time period. Acta Otolaryngol. 123, 148-153]. Eleven children who underwent CI between the age of 5 and 7 1/2 years were subdivided into a good (above 65%: GOOD) and a poor (below 45%: POOR) group based on the performance in a speech perception test given 2 years after CI. The preoperative (18)F-FDG-PET (F-18 fluorodeoxyglucose positron emission tomography) images were compared between the two groups in order to examine if regional glucose metabolic difference preexisted before the CI surgery. In the GOOD group, metabolic activity was greater in diverse fronto-parietal regions compared to the POOR group. In the POOR group, the regions related to the ventral visual pathway showed greater metabolic activity relative to the GOOD group. These findings suggest that the deaf children who had developed greater executive and visuospatial functions subserved by the prefrontal and parietal cortices might be successful in auditory language learning after CI. On the contrary, greater dependency on the visual function subserved by the occipito-temporal region due to auditory deprivation may interfere with acquisition of auditory language after CI.

  13. 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.

    PubMed

    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

  14. Inhibition of energy metabolism by 2-methylacetoacetate and 2-methyl-3-hydroxybutyrate in cerebral cortex of developing rats.

    PubMed

    Rosa, R B; Schuck, P F; de Assis, D R; Latini, A; Dalcin, K B; Ribeiro, C A J; da C Ferreira, G; Maria, R C; Leipnitz, G; Perry, M L S; Filho, C S Dutra; Wyse, A T S; Wannmacher, C M D; Wajner, M

    2005-01-01

    Mitochondrial beta-ketothiolase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiencies are inherited neurometabolic disorders affecting isoleucine catabolism. Biochemically, beta-ketothiolase deficiency is characterized by intermittent ketoacidosis and urinary excretion of 2-methyl-acetoacetate (MAA), 2-methyl-3-hydroxybutyrate (MHB) and tiglylglycine (TG), whereas in MHBD deficiency only MHB and tiglylglycine accumulate. Lactic acid accumulation and excretion are also observed in these patients, being more pronounced in MHBD-deficient individuals, particularly during acute episodes of decompensation. Patients affected by MHBD deficiency usually manifest severe mental retardation and convulsions, whereas beta-ketothiolase-deficient patients present encephalopathic crises characterized by metabolic acidosis, vomiting and coma. Considering that the pathophysiological mechanisms responsible for the neurological alterations of these disorders are unknown and that lactic acidosis suggests an impairment of energy production, the objective of the present work was to investigate the in vitro effect of MAA and MHB, at concentrations varying from 0.01 to 1.0 mmol/L, on several parameters of energy metabolism in cerebral cortex from young rats. We observed that MAA markedly inhibited CO2 production from glucose, acetate and citrate at concentrations as low as 0.01 mmol/L. In addition, the activities of the respiratory chain complex II and succinate dehydrogenase were mildly inhibited by MAA. MHB, at 0.01 mmol/L and higher concentrations, strongly inhibited CO2 production from all tested substrates, as well as the respiratory chain complex IV activity. The other activities of the respiratory chain were not affected by these metabolites. The data indicate a marked blockage in the Krebs cycle and a mild inhibition of the respiratory chain caused by MAA and MHB. Furthermore, MHB inhibited total and mitochondrial creatine kinase activities, which was prevented by the

  15. Frequency-dependent changes in cerebral metabolic rate of oxygen during activation of human visual cortex.

    PubMed

    Vafaee, M S; Meyer, E; Marrett, S; Paus, T; Evans, A C; Gjedde, A

    1999-03-01

    To test the hypothesis that brain oxidative metabolism is significantly increased upon adequate stimulation, we varied the presentation of a visual stimulus to determine the frequency at which the metabolic response would be at maximum. The authors measured regional CMR(O2) in 12 healthy normal volunteers with the ECAT EXACT HR+ (CTI/Siemens, Knoxville, TN, U.S.A.) three-dimensional whole-body positron emission tomograph (PET). In seven successive activating conditions, subjects viewed a yellow-blue annular checkerboard reversing its contrast at frequencies of 0, 1, 4, 8, 16, 32, and 50 Hz. Stimulation began 4 minutes before and continued throughout the 3-minute dynamic scan. In the baseline condition, the subjects began fixating a cross hair 30 seconds before the scan and continued to do so for the duration of the 3-minute scan. At the start of each scan, the subjects inhaled 20 mCi of (15)O-O2 in a single breath. The CMR(O2) value was calculated using a two-compartment, weighted integration method. Normalized PET images were averaged across subjects and coregistered with the subjects' magnetic resonance imaging in stereotaxic space. Mean subtracted image volumes (activation minus baseline) of CMR(O2) then were obtained and converted to z statistic volumes. The authors found a statistically significant focal change of CMR(O2) in the striate cortex (x = 9; y = -89; z = -1) that reached a maximum at 4 Hz and dropped off sharply at higher stimulus frequencies.

  16. Cyclic nucleotide regulation of inositol lipid metabolism in rat cerebral cortex

    SciTech Connect

    Nicchitta, C.V.; Williamson, J.R.

    1986-05-01

    The authors have investigated the effects of compounds known to elevate cAMP levels and/or activate the cAMP dependent protein kinase on resting and stimulated inositol lipid metabolism in rat cortical slices and synaptosomes. In (/sup 3/H)-myo-inositol-labeled brain slices, carbamylcholine-stimulated accumulation of (/sup 3/H)-myo-inositol 1-phosphate (IP/sub 1/) was decreased 50% by forskolin (150..mu..M) isobutylmethylxantihine (IBMX) (1mM), 8-bromo cAMP (5mM) or 8-(4-chlorophenylthio) cAMP (5mM). In studies with synaptosomes, the incorporation of (/sup 32/Pi) into phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP/sub 2/) and phosphatidic acid (PA) was also reduced in the presence of forskolin or the cAMP phosphodiesterase inhibitors IBMX and RO20-1724 (+/-)-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone. In the presence of maximally effective concentrations of these agents, steady state PIP levels were reduced by 50% and PIP/sub 2/ and PA levels by 40%. The effects of these compounds on (/sup 32/Pi) labeling of the phosphoinositides and PA are consistent with an inhibition of flux through the inositide cycle, presumably through the action of cAMP. Such an inhibition may account for the reduction in carbamylcholine sensitive IP/sub 1/ accumulation observed in brain slices. These studies indicate that in rat brain, ..beta..-adrenergic stimulation may be involved in modulating the activity of muscarinic cholinergic agonists. This regulation appears to be at the level of inositol lipid metabolism.

  17. Cerebral metabolic rate of oxygen in obstructive sleep apnea at rest and in response to breath-hold challenge.

    PubMed

    Rodgers, Zachary B; Leinwand, Sarah E; Keenan, Brendan T; Kini, Lohith G; Schwab, Richard J; Wehrli, Felix W

    2016-04-01

    Obstructive sleep apnea (OSA) is associated with extensive neurologic comorbidities. It is hypothesized that the repeated nocturnal apneas experienced in patients with OSA may inhibit the normal apneic response, resulting in hypoxic brain injury and subsequent neurologic dysfunction. In this study, we applied the recently developedOxFlowMRI method for rapid quantification of cerebral metabolic rate of oxygen (CMRO2) during a volitional apnea paradigm. MRI data were analyzed in 11 OSA subjects and 10 controls (mean ± SD apnea-hypopnea index (AHI): 43.9 ± 18.1 vs. 2.9 ± 1.6 events/hour,P < 0.0001; age: 53.8 ± 8.2 vs. 45.3 ± 8.5 years,P = 0.027; BMI: 36.6 ± 4.4 vs. 31.9 ± 2.2 kg/m(2),P = 0.0064). Although total cerebral blood flow and arteriovenous oxygen difference were not significantly different between apneics and controls (P > 0.05), apneics displayed reduced baseline CMRO2(117.4 ± 37.5 vs. 151.6 ± 29.4 µmol/100 g/min,P = 0.013). In response to apnea, CMRO2decreased more in apneics than controls (-10.9 ± 8.8 % vs. -4.0 ± 6.7 %,P = 0.036). In contrast, group differences in flow-based cerebrovascular reactivity were not significant. Results should be interpreted with caution given the small sample size, and future studies with larger independent samples should examine the observed associations, including potential independent effects of age or BMI. Overall, these data suggest that dysregulation of the apneic response may be a mechanism for OSA-associated neuropathology. © The Author(s) 2015.

  18. Hypertension is the primary component of metabolic syndrome associated with pathologic features of kidney cancer.

    PubMed

    Kocher, Neil J; Rjepaj, Chris; Robyak, Haley; Lehman, Erik; Raman, Jay D

    2017-01-01

    To determine whether individual and/or cumulative components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia) are associated with pathologic features of kidney cancer. A review of our kidney tumor database identified 462 patients who underwent partial or radical nephrectomy for renal cell carcinoma. The NCEP ATP-III criteria were used to define metabolic syndrome (MetS). Linear fixed effects modeling and ordinal logistic regression examined the relationship between MetS (individual and cumulative components) and pathologic characteristics. Two hundred and seventy-eight men and 184 women with a median age of 58 years, BMI of 31 kg/m(2), tumor size of 3.7 cm, and nephrometry score of 6 were included. Ninety-seven (21 %) patients met NCEP ATP-III criteria for MetS. Hypertension was the only individual component of MetS associated with pathologic features of kidney cancer including increased tumor size [geometric mean ratio 1.17 (1.05-1.32), P = 0.03], higher tumor grade [OR 1.49 (1.03-2.17), P = 0.04], increasing nephrometry score [OR 1.77 (1.28-2.48), P = 0.001], and non-clear cell histology [OR 1.42 (1.01-2.02), P = 0.05]. Furthermore, combinations of MetS components were associated with increased tumor grade (P = 0.02), tumor stage (P = 0.02), nephrometry score (P ≤ 0.001), and non-clear cell histology (P = 0.02), only when hypertension was included. MetS is composed of four risk factors each implicated in carcinogenesis. We identified hypertension as the primary component associated with specific pathologic features of kidney cancer. Further studies are necessary to elucidate whether the effect of hypertension is a function of severity and/or chronicity.

  19. MELANCHOLIC DEPRESSION PREDICTION BY IDENTIFYING REPRESENTATIVE FEATURES IN METABOLIC AND MICROARRAY PROFILES WITH MISSING VALUES

    PubMed Central

    Nie, Zhi; Yang, Tao; Liu, Yashu; Lin, Binbin; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2014-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  20. Melancholic depression prediction by identifying representative features in metabolic and microarray profiles with missing values.

    PubMed

    Nie, Zhi; Yang, Tao; Liu, Yashu; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2015-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  1. Effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia on cerebral blood flow and metabolism, lactate, and extracellular glutamate in experimental head injury.

    PubMed

    Mori, K; Maeda, M; Miyazaki, M; Iwase, H

    1998-12-01

    The effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia were investigated to determine which temperature was more effective against compression-induced cerebral ischemia. Eighteen cats were anesthetized. The animals were divided into three groups according to deep-brain temperature (control, 37 degrees C; mild hypothermia, 33 degrees C; and moderate hypothermia, 29 degrees C). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, the latter by hydrogen clearance. Arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO2) and the cerebral metabolic rate of lactate (CMR lactate) were calculated. Extracellular glutamate was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero, and this ischemia was maintained for 5 min, after which the balloon was quickly deflated. All parameters were recorded over 6 h. Evans blue was injected to examine vascular permeability changes. CBF was decreased by 56% by mild hypothermia and by 77% by moderate hypothermia. Mild hypothermia had a coupled metabolic suppression whereas moderate hypothermia significantly increased AVDO2 and decreased ScvO2, producing a low CBF/CMRO2 (relative ischemia). After balloon deflation, all three groups showed reactive hyperemia, which was significantly reduced by mild and moderate hypothermia. CBF then decreased to 50% of pre-inflation values and ScvO2 decreased (post-ischemic hypoperfusion). CBF/CMRO2, ScvO2, and AVDO2 did not differ significantly between the three groups. After balloon deflation, all three groups showed increased CMR lactate, which was significantly reduced by mild and moderate hypothermia. Extracellular glutamate increased in control animals (3.8 +/- 1.72 microM), an effect most effectively suppressed in the mild hypothermia group (1.0 +/- 0.46 microM). Damaged

  2. Pilot study of positron emission tomography (PET) brain glucose metabolism to assess the efficacy of tongue and body acupuncture in cerebral palsy.

    PubMed

    Wong, Virginia C N; Sun, Jie-Guang; Yeung, David W C

    2006-06-01

    We aimed to assess the efficacy of tongue and body acupuncture with clinical function and brain glucose metabolism in children with a severe type of cerebral palsy. Four children were recruited. The motor function belonged to grade 5 of the Gross Motor Function Measure (i.e., completely nonambulatory). Daily tongue and body acupuncture was applied for 5 days a week for 8 weeks. The Functional Independence Scale for Children (WeeFIM), Clinical Global Impression Scale (CGIS), and positron emission tomography of the brain with [18F]fluorodeoxyglucose (FDG) were performed at baseline and after acupuncture. None of the children had any significant change in the Functional Independence Scale for Children score, despite the fact that all mothers scored 3 on the Clinical Global Impression Scale (i.e., 25% in improvement) in overall function. The brain glucose metabolism, however, showed a >10% increase in the frontal, parietal, temporal, and occipital cortices and cerebellum. Thus, a short course of tongue and body acupuncture was shown to increase brain glucose metabolism, despite lacking any clinical functional improvement seen during the eight-week course, possibly owing to the severity of the motor dysfunction and the short duration of treatment. The objective increase in brain glucose metabolism might serve as a surrogate marker for assessing the subclinical efficacy of an alternative treatment before any objective clinical improvement is evident. A larger-scale study for different degrees of severity of cerebral palsy and an impairment model should be undertaken to correlate clinical with neurometabolic change.

  3. Imaging the time-integrated cerebral metabolic activity with subcellular resolution through nanometer-scale detection of biosynthetic products deriving from (13)C-glucose.

    PubMed

    Takado, Yuhei; Knott, Graham; Humbel, Bruno M; Masoodi, Mojgan; Escrig, Stéphane; Meibom, Anders; Comment, Arnaud

    2015-11-01

    Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100 nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.

  4. Local cerebral metabolic effects of L-dopa therapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys

    SciTech Connect

    Porrino, L.J.; Burns, R.S.; Crane, A.M.; Palombo, E.; Kopin, I.J.; Sokoloff, L.

    1987-08-01

    The quantitative 2-deoxy(/sup 14/C) glucose autoradiographic method was used to map the distribution of alterations in local cerebral glucose utilization that accompanies clinically effective chronic L-dopa therapy of rhesus monkeys made parkinsonian by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This pattern of changes was compared to the effects of a similar treatment regimen in normal monkeys. L-Dopa was administered orally to normal and parkinsonian monkeys 3 times daily for 60-120 days prior to measurement of local cerebral glucose utilization. In parkinsonian monkeys treated with L-dopa, signs and symptoms of parkinsonism were controlled or suppressed, and widespread increases in glucose utilization were seen throughout the brain. Cerebral metabolic activity was increased both in areas rich in dopaminergic receptors, such as the caudate and putamen, and in nondopaminergic areas involved in motor functions. In many structures the rates of glucose utilization in L-dopa-treated parkinsonian monkeys were increased to levels that far exceeded rates measured in normal monkeys. In sharp contrast, similar treatment with L-dopa in normal monkeys had little if any effect on local cerebral glucose utilization. L-Dopa, then, appears to have an action in animals with selective lesions of the substantia nigra pars compacta produced by MPTP that is distinctly different from its effects in the normal monkey.

  5. Amyloid-β peptide absence in short term effects on kinase activity of energy metabolism in mice hippocampus and cerebral cortex.

    PubMed

    Ianiski, Francine R; Rech, Virginia C; Nishihira, Vivian S K; Alves, Catiane B; Baldissera, Matheus D; Wilhelm, Ethel A; Luchese, Cristiane

    2016-01-01

    Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-β did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase activity in mitochondrial-rich fraction in the group induced by amyloid-β, but for the cytosolic fraction, it has raised in the activity of pyruvate kinase activity in cerebral cortex. Further, meloxicam-loaded nanocapsules administration reduced adenylate kinase activity in the hippocampus of mice injected by amyloid-β. In conclusion we observed absence in short-term effects in kinases activities of energy metabolism in mice hippocampus and cerebral cortex using amyloid-β peptide model. These findings established the foundation to further study the kinases in phosphoryltransfer network changes observed in the brains of patients post-mortem with Alzheimer's disease.

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

    PubMed

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

    2012-06-01

    Nimodipine is the only medication shown to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH). Preliminary theories regarding the mechanism by which it prevents vasospasm have been challenged. The acute physiologic and metabolic effects of oral Nimodipine have not been examined in patients with poor-grade SAH. This is an observational study performed in 16 poor-grade SAH patients undergoing multimodality monitoring who received oral Nimodipine as part of routine clinical care. A total of 663 doses of Nimodipine were observed. Changes in physiologic measurements including MAP, CPP, ICP, P(bt)O(2), and CBF were examined. Administration of oral Nimodipine was associated with a 1.33 mmHg decrease in MAP (P < 0.001) and a 1.22 mmHg decrease in CPP (P < 0.001). When administration of Nimodipine was associated with MAP decreases, P(bt)O(2) (1.03 mmHg; P < 0.001) and CBF (0.39 ml/100 g/min; P = 0.002) also decreased. Despite CPP targeted therapy with vasopressor medication, oral Nimodipine was associated with a decrease in MAP and CPP. When Nimodipine administration was associated with a decrease in MAP, there were concomitant drops in P(bt)O(2) and CBF. These findings suggest that MAP support after oral Nimodipine may be important to maintain adequate CBF in patients with poor-grade subarachnoid hemorrhage.

  7. Imaging based magnetic resonance spectroscopy (MRS) localization for quantitative neurochemical analysis and cerebral metabolism studies.

    PubMed

    Lee, Phil; Adany, Peter; Choi, In-Young

    2017-01-10

    Accurate quantitative metabolic imaging of the brain presents significant challenges due to the complexity and heterogeneity of its structures and compositions with distinct compartmentations of brain tissue types (e.g., gray and white matter). The brain is compartmentalized into various regions based on their unique functions and locations. In vivo magnetic resonance spectroscopy (MRS) techniques allow non-invasive measurements of neurochemicals in either single voxel or multiple voxels, yet the spatial resolution and detection sensitivity of MRS are significantly lower compared with MRI. A fundamentally different approach, namely spectral localization by imaging (SLIM) provides a new framework that overcomes major limitations of conventional MRS techniques. Conventional MRS allows only rectangular voxel shapes that do not conform to the shapes of brain structures or lesions, while SLIM allows compartments with arbitrary shapes. However, the restrictive assumption proposed in the original concept of SLIM, i.e., compartmental homogeneity, led to spectral localization errors, which have limited its broad applications. This review focuses on the recent technical frontiers of image-based MRS localization techniques that overcome the limitations of SLIM through the development and implementation of various new strategies, including incorporation of magnetic field inhomogeneity corrections, the use of multiple receiver coils, and prospective optimization of data acquisition.

  8. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    SciTech Connect

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I. )

    1990-03-01

    Regional CMRglc (rCMRglc) values were measured with ({sup 18}F)2-fluoro-2-deoxy-D-glucose ({sup 18}FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

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

    PubMed

    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.

  10. Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance: a double-blind, randomised, placebo-controlled trial.

    PubMed

    Kennedy, David O; Stevenson, Emma J; Jackson, Philippa A; Dunn, Sarah; Wishart, Karl; Bieri, Gregor; Barella, Luca; Carne, Alexandra; Dodd, Fiona L; Robertson, Bernadette C; Forster, Joanne; Haskell-Ramsay, Crystal F

    2016-01-01

    The brain is by far the most metabolically active organ in the body, with overall energy expenditure and local blood-supply closely related to neural activity. Both energy metabolism and cerebral vaso-dilation are dependent on adequate micronutrient status. This study investigated whether supplementation with ascending doses of multi-vitamin/minerals could modulate the metabolic and cerebral blood-flow consequences of performing cognitive tasks that varied in difficulty. In this randomised, double-blind, placebo-controlled, parallel-groups study 97 healthy females (25-49 y), who were not selected on the basis of any nutritional parameters, received either placebo or one of two doses of multivitamins/minerals. Cerebral blood-flow (CBF) parameters in the frontal cortex, and total energy expenditure (TotalEnergy), carbohydrate and fat oxidation (CarbOxi/FatOxi), were measured during 5 tasks of graded cognitive difficulty and a control task (5 min per task) using Near-infrared spectroscopy (NIRS) and Indirect calorimetry of exhaled pulmonary gas (ICa) respectively. Assessments took place 60 min after the first dose and following eight weeks supplementation. During task performance supplementation with the first dose of micronutrients led to a dose-dependent increase in TotalEnergy and FatOxi throughout the post-dose assessment period following the higher dose, and increases in the total concentration of haemoglobin, a proxy measure for CBF, during task performance following the lower dose of vitamins/minerals (also containing coenzyme-Q10). Chronic supplementation over 8 weeks led to a dose-dependent increase in TotalEnergy during the task period. There were no interpretable effects on mood or cognitive performance. These results show that acute supplementation with micronutrients in healthy adults can modulate metabolic parameters and cerebral blood flow during cognitive task performance, and that the metabolic consequences are sustained during chronic supplementation

  11. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer

    PubMed Central

    Chiche, Johanna; Brahimi-Horn, M Christiane; Pouysségur, Jacques

    2010-01-01

    Abstract Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na+/H+ exchangers, the proton pump, the monocarboxylate transporters, the HCO3− transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy. PMID:20015196

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

    PubMed

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

    2014-10-01

    Compared with goal-directed crystalloid therapy, goal-directed colloid therapy during high-risk surgery may improve postoperative outcome. Whether intraoperative fluid therapy based on goal-directed protocol with different types of fluid has distinctive effects on brain relaxation and cerebral metabolism during craniotomy remains unclear. Forty patients with supratentorial brain tumors undergoing craniotomy were randomly assigned to either a Ringer's Lactate-based goal-directed group (LR group, n=20) or a 6% hydroxyethyl starch-based goal-directed group (HES group, n=20). The goal was achieved by maintaining a target stroke volume variation (SVV<13%) by volume loading with LR or HES throughout the procedure. The primary outcome is brain relaxation scales, an indirect evaluation of ICP; secondary endpoints include cerebral metabolism variables (jugular venous oxygen saturation [SjvO(2)], arterial-jugular venous differences in oxygen [CajvO(2)], glucose [A-JvGD], lactate [A-JvLD], and cerebral extraction ratio for oxygen [CERO(2)]) and fluid volumes. There is no significant difference between the LR and HES groups on brain relaxation scales (P=0.845), or measures of cerebral oxygenation and metabolism. Intragroup comparisons showed that CERO(2) increased by 14.3% (P=0.009, LR group) and 13.2% (P=0.032, HES group), respectively, and SjvO(2) was decreased by 8.8% (P=0.016, LR group) and 8.1% (P=0.026, HES group), respectively, after tumor removal, compared with baseline. During surgery, the LR group (3070±1138 mL) received more fluid than the HES group (2041±758 mL, P=0.002). In patients undergoing supratentorial tumor resection, goal-directed HES therapy was not superior to goal-directed LR therapy for brain relaxation or cerebral metabolism, although less fluid was needed to maintain the target SVV in the HES-based group than in the LR-based group.

  13. Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study

    PubMed Central

    Njemanze, Philip C.; Kranz, Mathias; Amend, Mario; Hauser, Jens; Wehrl, Hans; Brust, Peter

    2017-01-01

    Introduction Color processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women. Materials and Methods The present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition. Results PET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice. Conclusions This study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease. PMID:28723938

  14. Chronic Exposure to β-Alanine Generates Oxidative Stress and Alters Energy Metabolism in Cerebral Cortex and Cerebellum of Wistar Rats.

    PubMed

    Gemelli, Tanise; de Andrade, Rodrigo Binkowski; Rojas, Denise Bertin; Zanatta, Ângela; Schirmbeck, Gabriel Henrique; Funchal, Cláudia; Wajner, Moacir; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2017-08-24

    β-Alanine occurs naturally in the human central nervous system and performs different functions. It can act as either a neurotransmitter or a neuromodulator, depletion of taurine levels and competitive antagonist of γ-aminobutyric acid (GABA). The β-amino acid accumulation exerts an important biological function as delay in brain development, oxidative stress and disturbances in energy metabolism, characterized as an inborn error of metabolism classified as β-alaninemia. We evaluated the effects of the chronic administration of β-alanine on some parameters of oxidative stress and enzymes of energy metabolism in cerebral cortex and cerebellum of 21-day-old Wistar rats. The animals received peritoneal injections of β-alanine (300 mg/kg of body weight), and the controls received the same volume (10 μl/g of body weight) of saline solution (NaCl 0.9%), twice a day at 12-h interval, from the 7th to the 21st postpartum day. We observed that β-amino acid was able to increase the levels of reactive oxygen species (ROS) in the two tissues; however, only in cerebral cortex total content of sulfhydryl was increased. ROS are possibly acting on antioxidant enzymes glutathione peroxidase (GPx) (cerebral cortex and cerebellum) and superoxide dismutase (SOD) (cerebellum) inhibiting their activities. We also evaluated the activities of enzymes of the phosphoryl transfer network, where we observed an increase in hexokinase and cytosolic creatine kinase (Cy-CK) activities; however, it decreased glyceraldehyde 3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) activities, in both tissues. Besides, the β-alanine administration increased the activities of complex II, complex IV and succinate dehydrogenase (SDH). Those results suggest that the chronic administration of β-alanine causes cellular oxidative damage, significantly changing the energy metabolism.

  15. Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray.

    PubMed

    Ritz, Marie-Françoise; Grond-Ginsbach, Caspar; Kloss, Manja; Tolnay, Markus; Fluri, Felix; Bonati, Leo H; Traenka, Christopher; Zeis, Thomas; Schaeren-Wiemers, Nicole; Peters, Nils; Engelter, Stefan Thomas; Lyrer, Philippe Alexandre

    2016-01-01

    Cerebral small-vessel disease (SVD) is characterized by periventricular white matter (WM) changes and general brain atrophy. SVD is prevalent in elderly individuals and is frequently associated with the development of vascular dementia (VaD). Studies of the molecular basis of SVD are sparse. We have to gain further insight into the pathogenic mechanisms of SVD. Therefore, we compared gene expression patterns in the brains of SVD and control patients, in order to identify cellular pathways changed in diseased brains. We compared the expression of mRNA transcripts in postmortem, macroscopically normal-appearing human brain tissues isolated from frontal, temporal and occipital cortical and subcortical regions in 5 SVD and 5 non-SVD control patients. Significant expression changes were determined by fold change F>1.2 in either direction, and p<0.05. We identified 228 genes differentially expressed in cortex (89 up-, 139 down-regulated) and 555 genes in WM (223 up-, 332 down-regulated) in SVD patients. Pathway analyses revealed that upregulated genes were associated with inflammation and apoptosis in WM, suggesting active cell death. Downregulated genes were associated with coagulation and fatty and amino acids metabolisms. In the cortex, down-regulated genes were principally associated with neuronal functions. Our data revealed widespread changes in the transcriptome profiles in the cortex and WM of human SVD brains, with a predominance of changes in WM. We provide for the first time a comprehensive view of the molecular alterations in human SVD brains that seem to contribute to the neuropathogenesis of SVD.

  16. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential

    PubMed Central

    Knudsen, Erik S.; Balaji, Uthra; Freinkman, Elizaveta; McCue, Peter; Witkiewicz, Agnieszka K.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from primary PDAC exhibited a high basal level of hypoxia inducible factor 1a (HIF1α) that was both required and sufficient to modulate the expression of MCT4. This event was associated with increased transcription and protein synthesis of HIF1α in CAFs relative to PDAC cell lines, while surprisingly the protein turnover rate was equivalent. CAFs utilized glucose predominantly for glycolytic intermediates, whereas glutamine was the preferred metabolite for the TCA cycle. Unlike PDAC cell lines, CAFs were resistant to glucose withdrawal but sensitive to glutamine depletion. Consistent with the lack of reliance on glucose, CAFs could survive the acute depletion of MCT4. In co-culture and xenograft studies CAFs stimulated the invasive potential and metastatic spread of PDAC cell lines through a mechanism dependent on HIF1α and MCT4. Together, these data indicate that stromal metabolic features influence PDAC tumor cells to promote invasiveness and metastatic potential and associate with poor outcome in patients with PDAC. PMID:27623078

  17. [The specific features of copper and manganese metabolism in the use of iron-containing preparations].

    PubMed

    Zaĭtseva, I P; Nasolodin, V V; Zaĭtsev, O N; Gladkikh, I P; Dvorkin, V A

    2012-01-01

    To comparatively evaluate the efficiency of preventive treatment with various iron preparations on copper, manganese, and iron metabolic features in adult athletes. Forty adult highly qualified sambo wrestlers were examined and divided into 4 groups of 10 persons in each. Group 1 athletes took iron-containing Sorbifer Durules in combination with ascorbic acid; Group 2 received Ferro Gradumet Vitamin C; Group 3 had Hemofer and ascorbic acid; Group 4 took ascorbic acid tablets. The latter group served as a control. Blood samples (15-20 ml) to be tested were taken at the beginning and end of 2-week use of iron preparations. The daily balance of iron, copper, and manganese was estimated following 7-day intake of these preparations. The use of iron-containing preparations in combination with ascorbic acid was ascertained to be accompanied by an increment in the plasma concentration of iron and blood corpuscles, indicating an increased need for this biotic and its deficiency in athletes. When the dose of iron was increased in the iron preparations, there was a substantial rise in the excretion of copper, manganese in particular, through the gastrointestinal tract and kidney and a negative balance of these trace elements in the body. Dietary addition of foods containing large amounts of ferrous iron, copper, and manganese is indicated for athletes exposed to higher intensity exercises.

  18. The use of complementary and alternative medicine by individuals with features of metabolic syndrome.

    PubMed

    Akilen, Rajadurai; Pimlott, Zeller; Tsiami, Amalia; Robinson, Nicola

    2014-05-01

    To compare the use of complementary and alternative medicine (CAM), including dietary supplements, by individuals with and without features of metabolic syndrome (FeMS). Using a cross sectional study design, information was obtained by self-administered questionnaires from 300 university individuals. FeMS was defined as any individuals self-reporting at least one of the clinical diagnoses of diabetes, hypertension, hyperlipidemia, or obesity. Finally, two categories were created for cross tabulation, and individuals with and without FeMS were compared. Of the 192 individuals completing the study, 39% (n=76) were currently using or had used CAM therapies in the past 12 months. Individuals with FeMS (n=54, 28%) were more likely (P<0.05) to use different types of CAM therapies, in particular dietary and herbal supplements, aromatherapy and massage therapy compared to individuals without FeMS (n=138, 72%). Individuals with FeMS were more likely to use CAM, particularly supplements. Doctors need to properly inquire about and understand their patients' supplement use, especially if CAM therapies are used in conjunction with conventional medications.

  19. A Mouse Model of Diet-Induced Obesity Resembling Most Features of Human Metabolic Syndrome

    PubMed Central

    Della Vedova, Maria C.; Muñoz, Marcos D.; Santillan, Lucas D.; Plateo-Pignatari, Maria G.; Germanó, Maria J.; Rinaldi Tosi, Martín E.; Garcia, Silvina; Gomez, Nidia N.; Fornes, Miguel W.; Gomez Mejiba, Sandra E.; Ramirez, Dario C.

    2016-01-01

    Increased chicken-derived fat and fructose consumption in the human diet is paralleled by an increasing prevalence of obesity and metabolic syndrome (MS). Herein, we aimed at developing and characterizing a mouse model of diet-induced obesity (DIO) resembling most of the key features of the human MS. To accomplish this, we fed male C57BL/6J mice for 4, 8, 12, and 16 weeks with either a low-fat diet (LFD) or a high-chicken-fat diet (HFD) and tap water with or without 10% fructose (F). This experimental design resulted in the following four experimental groups: LFD, LFD + F, HFD, and HFD + F. Over the feeding period, and on a weekly basis, the HFD + F group had more caloric intake and gained more weight than the other experimental groups. Compared to the other groups, and at the end of the feeding period, the HFD + F group had a higher adipogenic index, total cholesterol, low-density lipoprotein cholesterol, fasting basal glycemia, insulin resistance, hypertension, and atherogenic index and showed steatohepatitis and systemic oxidative stress/inflammation. A mouse model of DIO that will allow us to study the effect of MS in different organs and systems has been developed and characterized. PMID:27980421

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Quantification of cerebral glucose metabolic rate in mice using 18F-FDG and small-animal PET.

    PubMed

    Yu, Amy S; Lin, Hong-Dun; Huang, Sung-Cheng; Phelps, Michael E; Wu, Hsiao-Ming

    2009-06-01

    The aim of this study was to evaluate various methods for estimating the metabolic rate of glucose utilization in the mouse brain (cMR(glc)) using small-animal PET and reliable blood curves derived by a microfluidic blood sampler. Typical values of (18)F-FDG rate constants of normal mouse cerebral cortex were estimated and used for cMR(glc) calculations. The feasibility of using the image-derived liver time-activity curve as a surrogate input function in various quantification methods was also evaluated. Thirteen normoglycemic C57BL/6 mice were studied. Eighteen blood samples were taken from the femoral artery by the microfluidic blood sampler. Tissue time-activity curves were derived from PET images. cMR(glc) values were calculated using 2 different input functions (one derived from the blood samples [IF(blood)] and the other from the liver time-activity curve [IF(liver)]) in various quantification methods, which included the 3-compartment (18)F-FDG model (from which the (18)F-FDG rate constants were derived), the Patlak analysis, and operational equations. The estimated cMR(glc) value based on IF(blood) and the 3-compartment model served as a standard for comparisons with the cMR(glc) values calculated by the other methods. The values of K(1), k(2), k(3), k(4), and K(FDG) estimated by IF(blood) and the 3-compartment model were 0.22 +/- 0.05 mL/min/g, 0.48 +/- 0.09 min(-1), 0.06 +/- 0.02 min(-1), 0.025 +/- 0.010 min(-1), and 0.024 +/- 0.007 mL/min/g, respectively. The standard cMR(glc) value was, therefore, 40.6 +/- 13.3 micromol/100 g/min (lumped constant = 0.6). No significant difference between the standard cMR(glc) and the cMR(glc) estimated by the operational equation that includes k(4) was observed. The standard cMR(glc) was also found to have strong correlations (r > 0.8) with the cMR(glc) value estimated by the use of IF(liver) in the 3-compartment model and with those estimated by the Patlak analysis (using either IF(blood) or IF(liver)). The (18)F

  2. Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical features, magnetic resonance imaging, histopathology, and immunohistochemistry.

    PubMed

    Jeon, Joon-Hyeok; Jung, Hae-Won; Jang, Hyo-Mi; Moon, Jong-Hyun; Park, Ki-Tae; Lee, Hee-Chun; Lim, Ha-Young; Sur, Jung-Hyang; Kang, Byeong-Teck; Ha, Jeongim; Jung, Dong-In

    2015-01-01

    The purpose of this study was to identify time-related changes in clinical, MRI, histopathologic, and immunohistochemical findings associated with ischemic stroke in dogs. Additionally, the association of cerebrospinal fluid (CSF) and tissue levels of interleukin (IL)-6 with clinical prognosis was assessed. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in nine healthy experimental dogs. The dogs were divided into three groups according to survival time and duration of the experimental period: group A (survived only 1 day), group B (1-week experimental period), and group C (2-week experimental period). Neurologic status was evaluated daily. Magnetic resonance imaging (MRI) was performed according to a predetermined schedule. Concentration of IL-6 in CSF was measured serially after ischemic stroke. Postmortem examination was performed for all experimental dogs. During histopathological examination, variable degrees of cavitation and necrosis due to neuronal cytopathic effects, such as pyknotic nuclei and cytoplasmic shrinkage, were observed on the affected side of the cerebral cortex in all dogs. Immunohistochemistry specific for IL-6 showed increased expression in the ischemic lesions. CSF IL-6 concentrations and ischemic lesion volumes 1 day after ischemic stroke were significantly higher in group A compared to groups B and C.

  3. A web-based communication system for integrated care in cerebral palsy: design features, technical feasibility and usability.

    PubMed

    Gulmans, Jitske; Vollenbroek-Hutten, Miriam M R; Visser, Jacqueline J W; Nijeweme-d'Hollosy, Wendy Oude; van Gemert-Pijnen, J E W C Lisette; van Harten, Wim H

    2010-01-01

    We developed a secure, web-based system for parent-professional and inter-professional communication. The aim was to improve communication in the care of children with cerebral palsy. We conducted a six-month trial of the system in three Dutch health-care regions. The participants were the parents of 30 cerebral palsy patients and 120 professional staff involved in their care. Information about system usage was extracted from the system's database. The experience of the parents and professionals was evaluated by a questionnaire after six months. The system proved to be technically robust and reliable. A total of 21 parents (70%) and 66 professionals (55%) used the system. The parents submitted 111 questions and 59 responses, with a mean of 5 questions (range 1-17) and 3 responses (range 1-9) per parent. The professionals submitted 79 questions and 237 responses, with a mean of 2 questions (range 1-8) and 4 responses (range 1-23) per professional. Most parents (95%) and some professionals (30%) reported value in using the system, which ranged from efficiency and accessibility to flexibility and transparency. The web-based communication system was technically feasible and produced improved parent-professional and inter-professional communication. It may be especially valuable if frequent interventions or consultations about a child's care are required, involving complex care networks of different professionals and organisations.

  4. The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

    NASA Astrophysics Data System (ADS)

    Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

    2007-07-01

    It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

  5. [Several features of the metabolism of the fast and slow muscles of Emys orbicularis tortoises].

    PubMed

    Lebedinskaia, I I; Ogorodnikova, L G

    1978-01-01

    In skeletal muscles of the tortoise E. orbicularis, studies have been made on the content of glycogen, lactic acid, on the activity of glucose-6-phosphatase and phosphorylase. Histochemical studies were made on the lipid content. Experiments were performed on fast and slow bundles from mm. iliofibularis, testo cervicalis and retractor capitis. For comparison, the same indices of carbohydrate metabolism were investigated in fast m. plantaris and slow m. soleus of rats. In rats, slow muscles exhibit aerobic metabolism, in fast muscles--anaerobic one. In tortoises, slow muscles exhibit intermediate type of metabolism. Fast muscles show an anaerobic type or metabolism which is less intensive than anaerobic metabolism in slow muscles. Significant differences in some of the indices of carbohydrate metabolism were found in muscles which perform different functions in the organism.

  6. Energy metabolism in hypoxia: reinterpreting some features of muscle physiology on molecular grounds.

    PubMed

    Cerretelli, Paolo; Gelfi, Cecilia

    2011-03-01

    An holistic approach for interpreting classical data on the adaptation of the animal and, particularly, of the human body to hypoxic stress was promoted by the discovery of HIF-1, the "master regulator" of cell hypoxic signaling. Mitochondrial production of ROS stabilizes the O(2)-regulated HIF-1α subunit of the HIF-1 dimer promoting transaction functions in a large number of potential target genes, activating transcription of sequences into RNA and, eventually, protein production. The aim of the present preliminary study is to assess whether adaptive changes in oxygen sensing and metabolic signaling, particularly in the control of energy turnover known to occur in cultured cells exposed to hypoxia, are detectable also in the muscles of animals and man. For the present analysis, data obtained from the proteome of the rat gastrocnemius and of the vastus lateralis muscle of humans together with functional measurements were compared with homologous data from hypoxic cultured cells. In particular, the following variables were assessed: (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure. Despite the limited number of observations and the differences in the experimental approach, some initial interesting results were obtained encouraging to pursue this innovative effort.

  7. Features of selenium metabolism in humans living under the conditions of North European Russia.

    PubMed

    Parshukova, Olga; Potolitsyna, Natalya; Shadrina, Vera; Chernykh, Aleksei; Bojko, Evgeny

    2014-08-01

    Selenium supplementation and its effects on Northerners have been little studied. The aim of our study was to assess the selenium levels of the inhabitants of North European Russia, the seasonal aspects of selenium supplementation, and the interrelationships between selenium levels and the levels of thyroid gland hormones. To study the particular features of selenium metabolism in Northerners over the course of 1 year, 19 healthy male Caucasian volunteers (18-21 years old) were recruited for the present study. The subjects were military guards in a Northern European region of Russia (Syktyvkar, Russia, 62°N latitude) who spent 6-10-h outdoors daily. The study was conducted over a 12-month period. Selenium levels, glutathione peroxidase (GP) activity, as well as total triiodothyronine (T3), total thyroxin (T4), free thyroxin, free triiodothyronine, and thyrotropin (TSH) levels, were determined in the blood serum. The study subjects showed low levels of plasma selenium throughout the year. We observed a noticeable decrease in plasma selenium levels during the period from May to August, with the lowest levels in July. Selenium levels in the military guards correlated with the levels of selenium-dependent GP enzyme activity throughout the year. Additionally, we demonstrated a significant correlation between selenium and pituitary-thyroid axis hormones (total T3, free T4, and TSH) in periods in which plasma selenium levels were lower than the established normal ranges. Over the course of 1 year, low levels of plasma selenium affect GP activity and thyroid hormone levels in humans living in North European Russia.

  8. PEG-induced osmotic stress in Mentha x piperita L.: Structural features and metabolic responses.

    PubMed

    Búfalo, Jennifer; Rodrigues, Tatiane Maria; de Almeida, Luiz Fernando Rolim; Tozin, Luiz Ricardo Dos Santos; Marques, Marcia Ortiz Mayo; Boaro, Carmen Silvia Fernandes

    2016-08-01

    The present study investigated whether osmotic stress induced by the exposure of peppermint (Mentha x piperita L.) to moderate and severe stress for short periods of time changes the plant's physiological parameters, leaf anatomy and ultrastructure and essential oil. Plants were exposed to two levels of polyethyleneglycol (50 g L(-1) and 100 g L(-1) of PEG) in a hydroponic experiment. The plants exposed to 50 g L(-1) maintained metabolic functions similar to those of the control group (0 g L(-1)) without changes in gas exchange or structural characteristics. The increase in antioxidant enzyme activity reduced the presence of free radicals and protected membranes, including chloroplasts and mitochondria. In contrast, the osmotic stress caused by 100 g L(-1) of PEG inhibited leaf gas exchange, reduced the essential oil content and changed the oil composition, including a decrease in menthone and an increase in menthofuran. These plants also showed an increase in peroxidase activity, but this increase was not sufficient to decrease the lipid peroxidation level responsible for damaging the membranes of organelles. Morphological changes were correlated with the evaluated physiological features: plants exposed to 100 g L(-1) of PEG showed areas with collapsed cells, increases in mesophyll thickness and the area of the intercellular space, cuticle shrinkage, morphological changes in plastids, and lysis of mitochondria. In summary, our results revealed that PEG-induced osmotic stress in M. x piperita depends on the intensity level of the osmotic stress applied; severe osmotic stress changed the structural characteristics, caused damage at the cellular level, and reduced the essential oil content and quality.

  9. Metabolic fingerprints of serum, brain, and liver are distinct for mice with cerebral and noncerebral malaria: a ¹H NMR spectroscopy-based metabonomic study.

    PubMed

    Ghosh, Soumita; Sengupta, Arjun; Sharma, Shobhona; Sonawat, Haripalsingh M

    2012-10-05

    Cerebral malaria (CM) is a life-threatening disease in humans caused by Plasmodium falciparum, leading to high mortality. Plasmodium berghei ANKA (PbA) infection in C57Bl/6 mice induces pathologic symptoms similar to that in human CM. However, experimental CM incidence in mice is variable, and there are no known metabolic correlates/fingerprints for the animals that develop CM. Here, we have used (1)H NMR-based metabonomics to investigate the metabolic changes in the mice with CM with respect to the mice that have noncerebral malaria (NCM) of the same batchmates with identical genetic backgrounds and infected simultaneously. The metabolic profile of the infected mice (both CM and NCM) was separately compared with the metabolite profile of uninfected control mice of same genetic background. The objective of this study was to search for metabolic changes/fingerprints of CM and identify the pathways that might be differentially altered in mice that succumbed to CM. The results show that brain, liver, and sera exhibit unique metabolic fingerprints for CM over NCM mice. Some of the major fingerprints are increased level of triglycerides, VLDL-cholesterol in sera of CM mice, and decreased levels of glutamine in the sera concomitant with increased levels of glutamine in the brain of the mice with CM. Moreover, glycerophosphocholine is decreased in both the brain and the liver of animals with CM, and myo-inositol and histamine are increased in the liver of CM mice. The metabolic fingerprints in brain, sera, and liver of mice with CM point toward perturbation in the ammonia detoxification pathway and perturbation in lipid and choline metabolism in CM specifically. The study helps us to understand the severity of CM over NCM and in unrevealing the specific metabolic pathways that are compromised in CM.

  10. Hemodynamic Changes Following Visual Stimulation and Breath-holding Provide Evidence for an Uncoupling of Cerebral Blood Flow and Volume from Oxygen Metabolism

    PubMed Central

    Donahue, Manus J.; Stevens, Robert D.; de Boorder, Michiel; Pekar, James J.; Hendrikse, Jeroen; van Zijl, Peter C.M.

    2010-01-01

    Functional neuroimaging is most commonly performed using the blood-oxygenation-level-depend (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO2). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, separate visual stimulation (14s flashing checkerboard) and breath-hold (4s exhale + 14s breath-hold) experiments were performed in parallel on healthy volunteers using BOLD, CBV-weighted (CBVw) and CBF-weighted (CBFw) fMRI. Following visual stimulation, the BOLD signal persisted for 33±5s (n=9) and was bi-phasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20±5s and 20±3s, respectively. Following breath-hold, the BOLD signal returned to baseline (23±7s) at the same time (p>0.05) as CBV (21±6s) and CBF (18±3s), without a post-stimulus undershoot. These data indicate that following visual activation, the BOLD undershoot is likely due to continued elevated CMRO2. Furthermore, persisting elevated CMRO2 is found when CBF and CBV have returned to baseline levels, providing evidence for an uncoupling of CBV and CBF responses from CMRO2 changes. Persisting elevated CMRO2 following elevated neuronal activity may be necessary to reverse neurotransmitter movements arising from excitatory postsynaptic currents. PMID:18797471

  11. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity

    PubMed Central

    Brahe, L K; Le Chatelier, E; Prifti, E; Pons, N; Kennedy, S; Hansen, T; Pedersen, O; Astrup, A; Ehrlich, S D; Larsen, L H

    2015-01-01

    Background: Gut microbial gene richness and specific bacterial species are associated with metabolic risk markers in humans, but the impact of host physiology and dietary habits on the link between the gut microbiota and metabolic markers remain unclear. The objective of this study was to identify gut metagenomic markers associated with estimates of insulin resistance, lipid metabolism and inflammation in obesity, and to explore whether the associations between metagenomic and metabolic markers persisted after adjustment for body fat, age and habitual dietary intake. Methods: Faecal DNA from 53 women with obesity was analysed through quantitative metagenomic sequencing and analysis, and a systematic search was performed for bacterial genes associated with estimates of insulin resistance, inflammation and lipid metabolism. Subsequently, the correlations between metagenomic species and metabolic markers were tested by linear regression models, with and without covariate adjustment. Results: One hundred and fourteen metagenomic species correlated with metabolic markers (P<0.001) including Akkermansia muciniphila, Bilophila wadsworthia, Bifidobacterium longum and Faecalibacterium prausnitzii, but also species not previously associated with metabolic markers including Bacteroides faecis and Dorea longicatena. The majority of the identified correlations between bacterial species and metabolic markers persisted after adjustment for differences in body fat, age and dietary macronutrient composition; however, the negative correlation with insulin resistance observed for B. longum and F. prausnitzii appeared to be modified by the intake of dietary fibre and fat, respectively. Conclusions: This study shows that several gut bacterial species are linked to metabolic risk markers in obesity, also after adjustment for potential confounders, such as long-term diet composition. The study supports the use of gut metagenomic markers for metabolic disease prediction and warrants

  12. Age-dependent changes of cerebral copper metabolism in Atp7b (-/-) knockout mouse model of Wilson's disease by [(64)Cu]CuCl2-PET/CT.

    PubMed

    Xie, Fang; Xi, Yin; Pascual, Juan M; Muzik, Otto; Peng, Fangyu

    2017-06-01

    Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([(64)C]CuCl2) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b (-/-) knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [(64)C]CuCl2 in Atp7b (-/-) knockout mice, PET quantitative analysis revealed low (64)Cu radioactivity in the brains of Atp7b (-/-) knockout mice at 7th weeks of age, compared with (64)Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [(64)C]CuCl2 as a tracer. Furthermore, age-dependent increase of (64)Cu radioactivity was detected in the brains of Atp7b (-/-) knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [(64)C]CuCl2-PET/CT study of Atp7b (-/-) knockout mice with orally administered [(64)Cu]CuCl2 as a tracer. The findings of this study support clinical use of [(64)Cu]CuCl2-PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

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

    PubMed Central

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

    2010-01-01

    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 (CMRO2). 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 (∼3.7×) subcortical than cortical BOLD responses relative to CMRO2 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 sub-cortical regions. PMID:18164629

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Investigating the effects of cerebrospinal fluid removal on cerebral blood flow and oxidative metabolism in infants with post-hemorrhagic ventricular dilatation.

    PubMed

    McLachlan, Peter J; Kishimoto, Jessica; Diop, Mamadou; Milej, Daniel; Lee, David S C; de Ribaupierre, Sandrine; St Lawrence, Keith

    2017-10-01

    BackgroundPost-hemorrhagic ventricular dilatation (PHVD) is predictive of mortality and morbidity among very-low-birth-weight preterm infants. Impaired cerebral blood flow (CBF) due to elevated intracranial pressure (ICP) is believed to be a contributing factor.MethodsA hyperspectral near-infrared spectroscopy (NIRS) method of measuring CBF and the cerebral metabolic rate of oxygen (CMRO2) was used to investigate perfusion and metabolism changes in patients receiving a ventricular tap (VT) based on clinical management. To improve measurement accuracy, the spectral analysis was modified to account for compression of the cortical mantle caused by PHVD and the possible presence of blood breakdown products.ResultsFrom nine patients (27 VTs), a significant CBF increase was measured (15.6%) following VT (14.6±4.2 to 16.9±6.6 ml/100 g/min), but with no corresponding change in CMRO2 (1.02±0.41 ml O2/100 g/min). Post-VT CBF was in good agreement with a control group of 13 patients with patent ductus arteriosus but no major cerebral pathology (16.5±7.7 ml/100 g/min), whereas tissue oxygen saturation (StO2) was significantly lower (58.9±12.1% vs. 70.5±9.1% for controls).ConclusionCBF was impeded in PHVD infants requiring a clinical intervention, but the effect is not large enough to alter CMRO2.

  17. GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment.

    PubMed

    Schnepp, Patricia M; Lee, Dennis D; Guldner, Ian H; O'Tighearnaigh, Treasa K; Howe, Erin N; Palakurthi, Bhavana; Eckert, Kaitlyn E; Toni, Tiffany A; Ashfeld, Brandon L; Zhang, Siyuan

    2017-04-11

    The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downegulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell co-culture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacological disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo. Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting.

  18. Control of the cerebral circulation and metabolism by the rostral ventrolateral medulla: Possible role in the cerebrovascular response to hypoxia

    SciTech Connect

    Underwood, M.D.

    1988-01-01

    Neurons within the rostral ventrolateral medulla (RVL) corresponding to the location of adrenaline neurons of the C1 group (C1 area) maintain resting levels of arterial pressure (AP) and mediate the reflex cardiovascular responses to baro- and chemoreceptor activation and cerebral ischemia. The author therefore sought to determine whether neurons in the C1 area: (a) modulate regional cerebral blood flow (rCBF) and/or cerebral glucose utilization (rCGU), (b) participate in the maintenance of resting levels of CBF and CGU, and (c) mediate the CBF response to hypoxia. Rats were anesthetized, paralyzed and ventilated. The RVL was stimulated electrically or chemically, with kainic acid; lesions were placed electrolytically. rCBF was measured using 14-C-iodoantipyrine and rCGU with {sup 14}C-2-deoxyglucose in 11 dissected brain regions.

  19. Hypovitaminosis D in type 2 diabetes: relation with features of the metabolic syndrome and glycemic control.

    PubMed

    Miñambres, Inka; Sánchez-Quesada, Jose Luis; Vinagre, Irene; Sánchez-Hernández, Joan; Urgell, Eulalia; de Leiva, Alberto; Pérez, Antonio

    2015-01-01

    To assess the association of hypovitaminosis D with clinical and biochemical characteristics of type 2 diabetic patients and to determine the effect of glycemic control optimization on 25-hydroxyvitamin D (25(OH)D) concentrations. Cross-sectional study of 63 patients with type 2 diabetes (mean age 60 ± 9.8 years, 69.8% men). Twenty of the 63 patients were also studied before and after glycemic control optimization. Mean 25(OH)D concentrations were 63.64 ± 25.51 nmol/L and 74.6% of patients had hypovitaminosis D. Compared with patients with vitamin D sufficiency, patients with hypovitaminosis D had higher prevalence of overweight or obesity (72.3% versus 37.5%; p = 0.012) and higher VLDL cholesterol (VLDL-c) (0.71 (0.24-3.59) versus 0.45 (0.13-1.6) mmol/L; p = 0.011) and C-reactive protein (3.28 (0.36-17.69) versus 1.87 (0.18-17.47) mg/L; p = 0.033) concentrations. The composition of HDL particles also differed in both groups, with higher relative content of triglycerides and lower of cholesterol in patients with hypovitaminosis D. After adjustment for age, seasonality and BMI, differences remained significant for VLDL-c and triglyceride content of HDL. No differences were found regarding other diabetes characteristics. Improvement of glycemic control (HbA1c 9.4 (7.6-14.8) versus 7.3 (6.2-8.7)%; p = 0.000) was accompanied by a decrease in 25(OH)D concentrations (72.7 ± 33.3 to 59.0 ± 21.0 nmol/L; p = 0.035). Correlation analysis revealed that changes in 25(OH)D concentrations were negatively associated to changes in HbA1c (r - 0.482; p = 0.032). Hypovitaminosis D is associated with features of the metabolic syndrome in type 2 diabetes and improvement of glycemic control decreases 25(OH)D concentrations.

  20. New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature.

    PubMed Central

    Vérin, M; Rolland, Y; Landgraf, F; Chabriat, H; Bompais, B; Michel, A; Vahedi, K; Martinet, J P; Tournier-Lasserve, E; Lemaitre, M H

    1995-01-01

    A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities. To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31). Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia. This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym "cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and migraine" (CADASILM) is proposed to better describe this particular subvariety of CADASIL. Images PMID:7500094

  1. Multi-Omics of Tomato Glandular Trichomes Reveals Distinct Features of Central Carbon Metabolism Supporting High Productivity of Specialized Metabolites.

    PubMed

    Balcke, Gerd U; Bennewitz, Stefan; Bergau, Nick; Athmer, Benedikt; Henning, Anja; Majovsky, Petra; Jiménez-Gómez, José M; Hoehenwarter, Wolfgang; Tissier, Alain

    2017-05-01

    Glandular trichomes are metabolic cell factories with the capacity to produce large quantities of secondary metabolites. Little is known about the connection between central carbon metabolism and metabolic productivity for secondary metabolites in glandular trichomes. To address this gap in our knowledge, we performed comparative metabolomics, transcriptomics, proteomics, and (13)C-labeling of type VI glandular trichomes and leaves from a cultivated (Solanum lycopersicum LA4024) and a wild (Solanum habrochaites LA1777) tomato accession. Specific features of glandular trichomes that drive the formation of secondary metabolites could be identified. Tomato type VI trichomes are photosynthetic but acquire their carbon essentially from leaf sucrose. The energy and reducing power from photosynthesis are used to support the biosynthesis of secondary metabolites, while the comparatively reduced Calvin-Benson-Bassham cycle activity may be involved in recycling metabolic CO2 Glandular trichomes cope with oxidative stress by producing high levels of polyunsaturated fatty acids, oxylipins, and glutathione. Finally, distinct mechanisms are present in glandular trichomes to increase the supply of precursors for the isoprenoid pathways. Particularly, the citrate-malate shuttle supplies cytosolic acetyl-CoA and plastidic glycolysis and malic enzyme support the formation of plastidic pyruvate. A model is proposed on how glandular trichomes achieve high metabolic productivity. © 2017 American Society of Plant Biologists. All rights reserved.

  2. High Prevalence of Metabolic Syndrome Features in Patients Previously Treated for Nonfunctioning Pituitary Macroadenoma

    PubMed Central

    Joustra, Sjoerd D.; Claessen, Kim M. J. A.; Dekkers, Olaf M.; van Beek, André P.; Wolffenbuttel, Bruce H. R.; Pereira, Alberto M.; Biermasz, Nienke R.

    2014-01-01

    Objective Patients treated for nonfunctioning pituitary macroadenoma (NFMA) with suprasellar extension show disturbed sleep characteristics, possibly related to hypothalamic dysfunction. In addition to hypopituitarism, both structural hypothalamic damage and sleep restriction per se are associated with the metabolic syndrome. However, the prevalence of the metabolic syndrome in patients with NFMA is not well established. Our objective was to study the prevalence and risk factors for (components of) the metabolic syndrome in patients treated for NFMA. Design The metabolic syndrome (NCEP-ATP III criteria) was studied in an unselected cohort of 145 NFMA patients (aged 26–88yr, 44% female) in long-term remission after treatment, receiving adequate stable hormone replacement for any pituitary deficiencies. The results were compared to population data of 63,995 Dutch inhabitants by standardization (LifeLines cohort study). Results NFMA patients showed increased risk for reduced HDL-cholesterol (SMR 1.59, 95% CI 1.13–2.11), increased triglyceride levels (SMR 2.31, 95% CI 1.78–2.90) and the metabolic syndrome (SMR 1.60, 95% CI 1.22–2.02), but not for increased blood pressure, waist circumference or hyperglycemia. Preoperative visual field defects independently affected the risk for increased blood pressure (OR 6.5, 95% CI 1.9–22.2), and hypopituitarism was associated with a body mass index - dependent risk for increased waist circumference (OR 1.6, 95% CI 1.2–2.2) and the metabolic syndrome (OR 1.4, 95% CI 1.0–1.9). Conclusions Patients treated for NFMA are increased at risk for developing the