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VIOLA Angèle

DR CNRS

angele.viola@univ-amu.fr
tel : +33 4 91 32 48 04
Key Words
- Magnetic resonance (imaging and spectroscopy)
- Small animal brain

Current Research Interest and projects

Publications

2017

Journal Article

  • LAROCHE M., ALMERAS L., PECCHI E., BECHAH Y., RAOULT D., VIOLA A., PAROLA P. “MALDI-TOF MS as an innovative tool for detection of Plasmodium parasites in Anopheles mosquitoes.”. Malaria Journal [En ligne]. 2017. Vol. 16, n°1, p. 5. Disponible sur : < http://dx.doi.org/10.1186/s12936-016-1657-z > (consulté le no date)
    Résumé : BACKGROUND: Malaria is still a major public health issue worldwide, and one of the best approaches to fight the disease remains vector control. The current methods for mosquito identification include morphological methods that are generally time-consuming and require expertise, and molecular methods that require laboratory facilities with relatively expensive running costs. Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) technology, routinely used for bacterial identification, has recently emerged in the field of entomology. The aim of the present study was to assess whether MALDI-TOF MS could successfully distinguish Anopheles stephensi mosquitoes according to their Plasmodium infection status. METHODS: C57BL/6 mice experimentally infected with Plasmodium berghei were exposed to An. stephensi bites. For the determination of An. stephensi infection status, mosquito cephalothoraxes were dissected and submitted to mass spectrometry analyses and DNA amplification for molecular analysis. Spectra were grouped according to mosquitoes' infection status and spectra quality was validated based on intensity and reproducibility within each group. The in-lab MALDI-TOF MS arthropod reference spectra database, upgraded with representative spectra from both groups (infected/non-infected), was subsequently queried blindly with cephalothorax spectra from specimens of both groups. RESULTS: The MALDI TOF MS profiles generated from protein extracts prepared from the cephalothorax of An. stephensi allowed distinction between infected and uninfected mosquitoes. Correct classification was obtained in blind test analysis for (79/80) 98.75% of all mosquitoes tested. Only one of 80 specimens, an infected mosquito, was misclassified in the blind test analysis. CONCLUSIONS: Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry appears to be a promising, rapid and reliable tool for the epidemiological surveillance of Anopheles vectors, including their identification and their infection status.
    Mots-clés : crmbm.

2015

Journal Article
  • COLLIGNON A., PERLES-BARBACARU A. T., ROBERT S., SILVY F., MARTINEZ E., CRENON I., GERMAIN S., GARCIA S., VIOLA A., LOMBARDO D., MAS E., BéRAUD E. “A pancreatic tumor-specific biomarker characterized in humans and mice as an immunogenic onco-glycoprotein is efficient in dendritic cell vaccination.”. Oncotarget. 2015. Vol. 6, n°27, p. 23462-23479.
    Résumé : Oncofetal fucose-rich glycovariants of the pathological bile salt-dependent lipase (pBSDL) appear during human pancreatic oncogenesis and are detected by themonoclonal antibody J28 (mAbJ28). We aimed to identify murine counterparts onpancreatic ductal adenocarcinoma (PDAC) cells and tissue and investigate the potential of dendritic cells (DC) loaded with this unique pancreatic tumor antigen to promote immunotherapy in preclinical trials. Pathological BSDLs purified from pancreatic juices of patients with PDAC were cleaved to generate glycosylated C-terminal moieties (C-ter) containing mAbJ28-reactive glycoepitopes. Immunoreactivity of the murine PDAC line Panc02 and tumor tissue to mAbJ28 was detected by immunohistochemistry and flow cytometry. C-ter-J28+ immunization promoted Th1-dominated immune responses. In vitro C-ter-J28+-loaded DCskewed CD3+ T-cells toward Th1 polarization. C-ter-J28+-DC-vaccinations selectively enhanced cell immunoreactivity to Panc02, as demonstrated by CD4+- and CD8+-T-cell activation, increased percentages of CD4+- and CD8+-T-cells and NK1.1+ cells expressing granzyme B, and T-cell cytotoxicity. Prophylactic and therapeutic C-ter-J28+-DC-vaccinations reduced ectopic Panc02-tumor growth, provided long-lasting protection from Panc02-tumor development in 100% of micebut not from melanoma, and attenuated progression of orthotopic tumors as revealed by MRI. Thusmurine DC loaded with pancreatic tumor-specific glycoepitope C-ter-J28+ induce efficient anticancer adaptive immunity and represent a potential adjuvant therapy for patients afflicted with PDAC.

  • MASI B., PERLES-BARBACARU T. - A., LAPRIE C., DESSEIN H., BERNARD M., DESSEIN A., VIOLA A. “In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis [corrected].”. PLoS neglected tropical diseases [En ligne]. 2015. Vol. 9, n°9, p. e0004036. Disponible sur : < http://dx.doi.org/10.1371/journal.pntd.0004036 > (consulté le no date)
    Résumé : BACKGROUND: Schistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: CBA/J mice were imaged at 11.75 T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83) with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers. CONCLUSIONS/SIGNIFICANCE: Our multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis.
    Mots-clés : crmbm.

2013

Journal Article

  • CONDUCTIER G., BRAU F., VIOLA A., LANGLET F., RAMKUMAR N., DEHOUCK B., LEMAIRE T., CHAPOT R., LUCAS L., ROVÈRE C., MAITRE P., HOSSEINY S., PETIT-PAITEL A., ADAMANTIDIS A., LAKAYE B., RISOLD P. - Y., PRÉVOT V., MESTE O., NAHON J. - L., GUYON A. “Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume.”. Nature Neuroscience [En ligne]. 2013. Vol. 16, n°7, p. 845-847. Disponible sur : < http://dx.doi.org/10.1038/nn.3401 > (consulté le no date)
    Résumé : Ependymal cell cilia help move cerebrospinal fluid through the cerebral ventricles, but the regulation of their beat frequency remains unclear. Using in vitro, high-speed video microscopy and in vivo magnetic resonance imaging in mice, we found that the metabolic peptide melanin-concentrating hormone (MCH) positively controlled cilia beat frequency, specifically in the ventral third ventricle, whereas a lack of MCH receptor provoked a ventricular size increase.
    Mots-clés : Adenosine Triphosphate, Animals, Brain, Calcium, Cerebral Ventricles, Cerebrospinal Fluid, Cilia, Electric Stimulation, Ependyma, Female, Hormone Antagonists, Hypothalamic Hormones, In Vitro Techniques, Male, Melanins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Pituitary Hormones, Receptors, Somatostatin, Serotonin.

  • CONDUCTIER G., VIOLA A., LE TROTER A., NAHON J. - L., GUYON A. “[Beating frequency of motile cilia lining the third cerebral ventricle is finely tuned by the hypothalamic peptide MCH].”. Médecine sciences: M/S [En ligne]. 2013. Vol. 29, n°11, p. 943-945. Disponible sur : < http://dx.doi.org/10.1051/medsci/20132911004 > (consulté le no date)

2012

Journal Article

  • LAIGLE C., CONFORT-GOUNY S., LE FUR Y., COZZONE P. J., VIOLA A. “Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia.”. PloS one [En ligne]. 2012. Vol. 7, n°12, p. e53266. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0053266 > (consulté le no date)
    Résumé : Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K⁺ channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K⁺ channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak⁻/⁻ mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak⁻/⁻ mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak⁺/⁺ mice. Upon ischemia, Traak⁻/⁻ mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak⁺/⁺ mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak⁻/⁻ mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke.
    Mots-clés : Animals, Brain, crmbm, Cytoprotection, Energy Metabolism, Female, Gene Deletion, Hypoxia-Ischemia, Brain, Infarction, Middle Cerebral Artery, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Potassium Channels.

  • MAGALON K., ZIMMER C., CAYRE M., KHALDI J., BOURBON C., ROBLES I., TARDIF G., VIOLA A., PRUSS R. M., BORDET T., DURBEC P. “Olesoxime accelerates myelination and promotes repair in models of demyelination.”. Annals of neurology [En ligne]. 2012. Vol. 71, n°2, p. 213-226. Disponible sur : < http://dx.doi.org/10.1002/ana.22593 > (consulté le no date)
    Résumé : OBJECTIVE: Multiple sclerosis is a neurodegenerative disease characterized by episodes of immune attack of oligodendrocytes leading to demyelination and progressive functional deficit. One therapeutic strategy to address disease progression could consist in stimulating the spontaneous regenerative process observed in some patients. Myelin regeneration requires endogenous oligodendrocyte progenitor migration and activation of the myelination program at the lesion site. In this study, we have tested the ability of olesoxime, a neuroprotective and neuroregenerative agent, to promote remyelination in the rodent central nervous system in vivo. METHODS: The effect of olesoxime on oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis was tested directly in organotypic slice cultures and OPC-neuron cocultures. Using naive animals and different mouse models of demyelination, we morphologically and functionally assessed the effect of the compound on myelination in vivo. RESULTS: Olesoxime accelerated oligodendrocyte maturation and enhanced myelination in vitro and in vivo in naive animals during development and also in the adult brain without affecting oligodendrocyte survival or proliferation. In mouse models of demyelination and remyelination, olesoxime favored the repair process, promoting myelin formation with consequent functional improvement. INTERPRETATION: Our observations support the strategy of promoting oligodendrocyte maturation and myelin synthesis to enhance myelin repair and functional recovery. We also provide proof of concept that olesoxime could be useful for the treatment of demyelinating diseases.
    Mots-clés : Animals, Cholestenones, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Monoamine Oxidase Inhibitors, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Rats, Rats, Sprague-Dawley.

2011

Journal Article

  • SAGGU R., FAILLE D., GRAU G. E., COZZONE P. J., VIOLA A. “In the eye of experimental cerebral malaria.”. The American journal of pathology [En ligne]. 2011. Vol. 179, n°3, p. 1104-1109. Disponible sur : < http://dx.doi.org/10.1016/j.ajpath.2011.05.044 > (consulté le no date)
    Résumé : Cerebral malaria is the most severe complication of Plasmodium falciparum infection, accounting for 1 million deaths per year. We characterized the murine disease using in vivo magnetic resonance imaging (MRI) at 4.7 T, proving that ischemic edema is responsible for fatality. The aim of the present study was to identify early markers of experimental cerebral malaria using very high field conventional MRI (11.75 T). CBA/J mice infected with Plasmodium berghei ANKA were observed at an early stage of the disease, before the onset of detectable brain swelling and at the most acute stage of cerebral malaria. Herein, we report the first detection of damage to the optic and trigeminal nerves on T(2)-weighted MRI. The trigeminal nerves appeared hypointense, with significantly reduced diameter and cross-sectional area. The optic nerves were hypointense and often not visible. In addition, the internerve distance between the optic nerves was significantly and progressively reduced between the early and severest stages. Cranial nerve injury was the earliest anatomic hallmark of the disease, visible before brain edema became detectable. Thus, cranial nerve damage may manifest in neurologic signs, which may assist in the early recognition of cerebral malaria.
    Mots-clés : Animals, Brain Edema, crmbm, Early Diagnosis, Female, Magnetic Resonance Imaging, Malaria, Cerebral, Mice, Mice, Inbred CBA, Optic Nerve Diseases, Plasmodium berghei, Trigeminal Nerve Diseases.

  • VIOLA A., CONFORT-GOUNY S., SCHNEIDER J. F., LE FUR Y., VIOUT P., CHAPON F., PINEAU S., COZZONE P. J., GIRARD N. “Is brain maturation comparable in fetuses and premature neonates at term equivalent age?”. AJNR. American journal of neuroradiology [En ligne]. 2011. Vol. 32, n°8, p. 1451-1458. Disponible sur : < http://dx.doi.org/10.3174/ajnr.A2555 > (consulté le no date)
    Résumé : BACKGROUND AND PURPOSE: Improved knowledge of brain maturation in fetuses and premature neonates is crucial for the early detection of pathologies and would help determine whether MR data from the premature brain might be used to evaluate fetal maturation. Using diffusion-weighted MR imaging and (1)H-MR spectroscopy, we compared cerebral microstructure and metabolism in normal in utero fetuses imaged near term and premature neonates imaged at term equivalent. MATERIALS AND METHODS: Forty-eight subjects were investigated: 24 in utero fetuses (mean gestational age, 37 ± 1 weeks) and 24 premature neonates (mean postconceptional age, 37 ± 1 weeks). ADC values were measured in cerebellum, pons, white matter, brain stem, basal ganglia, and thalamus. MR spectroscopy was performed in deep white matter. RESULTS: Mean ADC values from fetuses and premature neonates were comparable except for the pons and the parietal white matter. ADC values were lower in the pons of premature neonates, whereas greater values were found in their parietal white matter compared with fetuses. Proton MR spectroscopy showed higher levels of NAA/H(2)O, Glx/H(2)O, tCr/H(2)O, and mIns/H(2)O in premature neonates compared with fetuses. CONCLUSIONS: Our study provides evidence of subtle anomalies in the parietal white matter of healthy premature neonates. In addition, the reduced ADC values in the pons together with the increased levels of NAA/H(2)O, tCr/H(2)O, and Glx/H(2)O in the centrum semiovale suggest a more advanced maturation in some white matter regions. Our results indicate that MR data from the premature brain are not appropriate for the assessment of the fetal brain maturation.
    Mots-clés : Brain, crmbm, Fetal Organ Maturity, Fetus, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Term Birth.

2007

Journal Article
  • GALANAUD D., NICOLI F., CONFORT-GOUNY S., LE FUR Y., RANJEVA J. P., VIOLA A., GIRARD N., COZZONE P. J. “[Indications for cerebral MR proton spectroscopy in 2007].”. Revue neurologique. 2007. Vol. 163, n°3, p. 287-303.
    Résumé : Magnetic resonance spectroscopy (MRS) is being increasingly performed alongside the more conventional MRI sequences in the exploration of neurological disorders. It is however important to clearly differentiate its clinical applications aiming at improving the differential diagnosis or the prognostic evaluation of the patient, from the research protocols, when MRS can contribute to a better understanding of the pathophysiology of the disease or to the evaluation of new treatments. The most important applications in clinical practice are intracranial space occupying lesions (especially the positive diagnosis of intracranial abscesses and gliomatosis cerebri and the differential diagnosis between edema and tumor infiltration), alcoholic, hepatic, and HIV-related encephalopathies and the exploration of metabolic diseases. Among the research applications, MRS is widely used in multiple sclerosis, ischemia and brain injury, epilepsy and neuro degenerative diseases.
    Mots-clés : AIDS Dementia Complex, Brain, Brain Diseases, Brain Neoplasms, crmbm, Diagnosis, Differential, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Mitochondrial Myopathies, Nervous System Diseases.

  • GIRARD N., CONFORT-GOUNY S., SCHNEIDER J., BARBERET M., CHAPON F., VIOLA A., PINEAU S., COMBAZ X., COZZONE P. “MR imaging of brain maturation.”. Journal of Neuroradiology. Journal De Neuroradiologie [En ligne]. 2007. Vol. 34, n°5, p. 290-310. Disponible sur : < http://dx.doi.org/10.1016/j.neurad.2007.07.007 > (consulté le no date)
    Résumé : Magnetic resonance imaging (MRI) is the imaging tool of choice to evaluate brain maturation and especially brain myelination. Magnetic resonance imaging also provides functional insight through diffusion images and proton spectroscopy. In this review the MRI techniques are analyzed for both pre- and postnatal periods. The origin of MR signal changes is also detailed in order to understand normal myelination evolution and the consequences on brain maturation of the different pathologies encountered prior and after birth. Because MRI is "blind" in terms of signal on conventional sequences after 2 years of age, a particular attention is given to diffusion images and proton spectroscopy of the developing brain.
    Mots-clés : Brain, Child, Preschool, crmbm, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy.

  • GIRARD N., CONFORT-GOUNY S., SCHNEIDER J., CHAPON F., VIOLA A., PINEAU S., COMBAZ X., COZZONE P. “Neuroimaging of neonatal encephalopathies.”. Journal of Neuroradiology. Journal De Neuroradiologie [En ligne]. 2007. Vol. 34, n°3, p. 167-182. Disponible sur : < http://dx.doi.org/10.1016/j.neurad.2007.04.003 > (consulté le no date)
    Résumé : Neonatal brain disorders consist of a wide chapter including brain malformations, hypoxic-ischemic encephalopathy (HIE), intracranial infections, perinatal trauma and metabolic encephalopathy. We will focus here on HIE, intracranial infections (especially materno-fetal infection with or without prolonged and/or premature rupture of membranes) and metabolic encephalopathy, those three conditions being the most frequent so far in our experience. Neonatal stroke is also analyzed. Moreover minor perinatal events might be superimposed on an already damaged (infective, edematous, metabolically abnormal or maldeveloped) brain, highlighting the main role and potential benefits of neuroimaging during the neonatal period. The different methods of brain imaging are thus reported with their advantages and disadvantages.
    Mots-clés : Brain Diseases, crmbm, Diagnostic Imaging, Humans, Infant, Newborn.

  • LUTZ N. W., VIOLA A., MALIKOVA I., CONFORT-GOUNY S., AUDOIN B., RANJEVA J. - P., PELLETIER J., COZZONE P. J. “Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid.”. PloS one [En ligne]. 2007. Vol. 2, n°7, p. e595. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0000595 > (consulté le no date)
    Résumé : BACKGROUND: Multiple sclerosis (MS), an inflammatory disease of the central nervous system, manifests itself in numerous forms and stages. A number of brain metabolic alterations have been reported for MS patients vs. control subjects. However, metabolite profiles of cerebrospinal fluid (CSF) are not consistent among the published MS studies, most probably due to variations in the patient cohorts studied. We undertook the first investigation of highly homogeneous MS patient cohorts to determine characteristic effects of inflammatory MS plaques on the CSF metabolome, including only patients with clinically isolated syndrome (CIS) with or without inflammatory brain plaques, and controls. METHODOLOGY/PRINCIPAL FINDINGS: CSF obtained by lumbar puncture was analyzed by proton magnetic resonance spectroscopy. 27 metabolites were quantified. Differences between groups of control subjects (n = 10), CIS patients with (n = 21) and without (n = 12) inflammatory plaques were evaluated by univariate statistics and principal component analysis (PCA). Seven metabolites showed statistically significant inter-group differences (p<0.05). Interestingly, a significant increase in beta-hydroxyisobutyrate (BHIB) was detected in CIS with vs. without active plaques, but not when comparing either CIS group with control subjects. Moreover, a significant correlation was found, for the first time, between CSF lactate concentration and the number of inflammatory MS brain plaques. In contrast, fructose concentrations were equally enhanced in CIS with or without active plaques. PCA based on all 27 metabolites yielded group-specific clusters. CONCLUSIONS/SIGNIFICANCE: CSF metabolic profiles suggest a close link between MS plaque activity in CIS patients on the one hand and organic-acid metabolism on the other. Our detection of increased BHIB levels points to a hitherto unsuspected role for this compound in MS with active plaques, and serves as a basis for further investigation. The metabolic effects described in our study are crucial elements in the explanation of biochemical mechanisms involved in specific MS manifestations.
    Mots-clés : Adult, Amino Acids, Brain, Creatinine, crmbm, Female, Fructose, Glucose, Hemolytic Plaque Technique, Humans, Inflammation, Male, Middle Aged, Multiple Sclerosis, Syndrome.

  • LUTZ N. W., VIOLA A., MALIKOVA I., CONFORT-GOUNY S., RANJEVA J. - P., PELLETIER J., COZZONE P. J. “A branched-chain organic acid linked to multiple sclerosis: first identification by NMR spectroscopy of CSF.”. Biochemical and biophysical research communications [En ligne]. 2007. Vol. 354, n°1, p. 160-164. Disponible sur : < http://dx.doi.org/10.1016/j.bbrc.2006.12.169 > (consulté le no date)
    Résumé : (1)H NMR spectroscopy of cerebrospinal fluid (CSF) is currently being used to study metabolic profiles characteristic of distinct multiple sclerosis (MS) manifestations. For select MS patient groups, we have previously detected significantly increased concentrations of several identified metabolites and one unidentified compound. We now present, for the first time, the identification of the latter molecule, beta-hydroxyisobutyrate (BHIB). A combination of dedicated 1D and 2D (1)H NMR experiments was employed for signal assignment. To our knowledge, BHIB has not previously been identified in (1)H NMR spectra of biofluids or biological tissues. Our assignment suggests new biochemical pathways involved in specific MS pathologies.
    Mots-clés : Acids, Biological Markers, crmbm, Humans, Hydroxybutyrates, Magnetic Resonance Spectroscopy, Multiple Sclerosis, Organic Chemicals, Protons.

  • PENET M. - F., KOBER F., CONFORT-GOUNY S., LE FUR Y., DALMASSO C., COLTEL N., LIPRANDI A., GULIAN J. - M., GRAU G. E., COZZONE P. J., VIOLA A. “Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA.”. The Journal of Biological Chemistry [En ligne]. 2007. Vol. 282, n°19, p. 14505-14514. Disponible sur : < http://dx.doi.org/10.1074/jbc.M608035200 > (consulté le no date)
    Résumé : Malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. Severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. Using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of Plasmodium berghei ANKA on brain, in a mouse strain developing malaria but resistant to cerebral malaria. The purpose was to determine whether the infection could cause a brain dysfunction distinct from the classic cerebral syndrome. Mice resistant to cerebral malaria were infected with P. berghei ANKA and explored during both the symptomless and the severe stage of the disease by using in vivo brain magnetic resonance imaging and spectroscopy. The infected mice did not present the lesional and metabolic hallmarks of cerebral malaria. However, brain dysfunction caused by anemia, parasite burden, and hepatic damage was evidenced. We report an increase in cerebral blood flow, a process allowing temporary maintenance of oxygen supply to brain despite anemia. Besides, we document metabolic anomalies affecting choline-derived compounds, myo-inositol, glutamine, glycine, and alanine. The choline decrease appears related to parasite proliferation. Glutamine, myo-inositol, glycine, and alanine variations together indicate a hepatic encephalopathy, a finding in agreement with the liver damage detected in mice, which is also a feature of the human disease. These results reveal the vulnerability of brain to malaria infection at the severe stage of the disease even in the absence of cerebral malaria.
    Mots-clés : Alanine, Anemia, Animals, Brain, Brain Diseases, Brain Edema, Brain Ischemia, Cell Proliferation, Cerebrovascular Circulation, crmbm, Female, Liver, Magnetic Resonance Spectroscopy, Malaria, Cerebral, Mice, Mice, Inbred BALB C, Plasmodium berghei.

  • SCHNEIDER J. F., CONFORT-GOUNY S., VIOLA A., LE FUR Y., VIOUT P., BENNATHAN M., CHAPON F., FIGARELLA-BRANGER D., COZZONE P., GIRARD N. “Multiparametric differentiation of posterior fossa tumors in children using diffusion-weighted imaging and short echo-time 1H-MR spectroscopy.”. Journal of magnetic resonance imaging: JMRI [En ligne]. 2007. Vol. 26, n°6, p. 1390-1398. Disponible sur : < http://dx.doi.org/10.1002/jmri.21185 > (consulté le no date)
    Résumé : PURPOSE: To assess the combined value of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) in differentiating medulloblastoma, ependymoma, pilocytic astrocytoma, and infiltrating glioma in a pediatric population. MATERIALS AND METHODS: A total of 17 children with untreated posterior fossa tumors (seven medulloblastoma, four infiltrating glioma, two ependymoma, and four pilocytic astrocytoma), were investigated with conventional MRI, DWI, and MRS using a single-voxel technique. Within the nonnecrotic tumor core, apparent diffusion coefficient (ADC) values using a standardized region of interest (ROI) were retrieved. Quantification of water signal and analysis of metabolite signals from MRS measurements in the same tumorous area were reviewed using multivariant linear discriminant analysis. RESULTS: Combination of ADC values and metabolites, which were normalized using water as an internal standard, allowed discrimination between the four tumor groups with a likelihood below 1 x 10(-9). Positive predictive value was 1 in all cases. Tumors could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values. CONCLUSION: Linear discriminant analysis using DWI and MRS using water as internal reference, fully discriminates the four most frequent posterior fossa tumors in children.
    Mots-clés : Adolescent, Astrocytoma, Brain Neoplasms, Child, Child, Preschool, Cranial Fossa, Posterior, crmbm, Diagnosis, Differential, Diffusion Magnetic Resonance Imaging, Discriminant Analysis, Ependymoma, Female, Glioma, Humans, Infant, Magnetic Resonance Spectroscopy, Male, Medulloblastoma, Retrospective Studies, Statistics, Nonparametric.

  • SCHNEIDER J. F., VIOLA A., CONFORT-GOUNY S., AYUNTS K., LE FUR Y., VIOUT P., BENNATHAN M., CHAPON F., FIGARELLA-BRANGER D., COZZONE P., GIRARD N. “Infratentorial pediatric brain tumors: the value of new imaging modalities.”. Journal of neuroradiology. Journal de neuroradiologie [En ligne]. 2007. Vol. 34, n°1, p. 49-58. Disponible sur : < http://dx.doi.org/10.1016/j.neurad.2007.01.010 > (consulté le no date)
    Résumé : The correct assessment of the four most frequent infratentorial brain tumors in children (medulloblastoma, ependymoma, pilocytic astrocytoma and infiltrating glioma) has always been problematic. They are known to often resemble one another on conventional magnetic resonance (MR) imaging. We tested the hypothesis whether the combined strength of diffusion-weighted imaging (DWI) and proton MR spectroscopy (MRS) could help differentiate these tumors. Seventeen children with untreated posterior fossa tumors were investigated between January 2005 and January 2006 with conventional MR imaging and combined DWI and MR spectroscopy using a single-voxel technique at short and long echo time (TE) of 30 ms and 135 ms respectively. Apparent diffusion coefficient (ADC) values were retrieved after regions of interest were manually positioned within non necrotic tumor core. Water signal was quantified and metabolite signals were compared and analyzed using linear discriminant analysis. When a combination of ADC values and normalized metabolites was used, all tumors could be discriminated against one other. This could only be achieved when metabolites were normalized using water as an internal standard. They could not be discriminated when using metabolite ratios or ADC values alone, nor could they be differentiated using creatine (Cr) as an internal reference even in combination with ADC values. In conclusion, linear discriminant analysis and multiparametric combination of DWI and MRS, although not replacing histology, fully discriminates the four most frequent posterior fossa tumors in children, but metabolites have to be normalized using water and not Cr signal as an internal reference.
    Mots-clés : Adolescent, Child, Child, Preschool, crmbm, Diffusion Magnetic Resonance Imaging, Female, Glioma, Humans, Infratentorial Neoplasms, Magnetic Resonance Spectroscopy, Male, Reproducibility of Results, Retrospective Studies.

  • VIOLA A., SAYWELL V., VILLARD L., COZZONE P. J., LUTZ N. W. “Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model.”. PloS one [En ligne]. 2007. Vol. 2, n°1, p. e157. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0000157 > (consulté le no date)
    Résumé : BACKGROUND: Rett syndrome (RS) is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null") mouse have been employed to study neurological symptoms and brain function. However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate the mechanistic links between the genotype and phenotype of this genetic disorder. METHODOLOGY/PRINCIPAL FINDINGS: We performed, for the first time, a metabolomic study of brain extracts from Mecp2-null mice by using high-resolution magnetic resonance spectroscopy. A large number of individual water-soluble metabolites and phospholipids were quantified without prior selection for specific metabolic pathways. Results were interpreted in terms of Mecp2 gene deletion, brain cell function and brain morphology. This approach provided a "metabolic window" to brain characteristics in Mecp2-null mice (n = 4), revealing (i) the first metabolic evidence of astrocyte involvement in RS (decreased levels of the astrocyte marker, myo-inositol, vs. wild-type mice; p = 0.034); (ii) reduced choline phospholipid turnover in Mecp2-null vs. wild-type mice, implying a diminished potential of cells to grow, paralleled by globally reduced brain size and perturbed osmoregulation; (iii) alterations of the platelet activating factor (PAF) cycle in Mecp2-null mouse brains, where PAF is a bioactive lipid acting on neuronal growth, glutamate exocytosis and other processes; and (iv) changes in glutamine/glutamate ratios (p = 0.034) in Mecp2-null mouse brains potentially indicating altered neurotransmitter recycling. CONCLUSIONS/SIGNIFICANCE: This study establishes, for the first time, detailed metabolic fingerprints of perturbed brain growth, osmoregulation and neurotransmission in a mouse model of Rett syndrome. Combined with morphological and neurological findings, these results are crucial elements in providing mechanistic links between genotype and phenotype of Rett syndrome. Ultimately, this information can be used to identify novel molecular targets for pharmacological RS treatment.
    Mots-clés : Animals, Brain, Brain Chemistry, Cardiolipins, crmbm, Female, Genotype, Humans, Infant, Male, Methyl-CpG-Binding Protein 2, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurotransmitter Agents, Phenotype, Phospholipids, Rett Syndrome, Synaptic Transmission, Water-Electrolyte Balance.

2006

Journal Article

  • BERAUD E., VIOLA A., REGAYA I., CONFORT-GOUNY S., SIAUD P., IBARROLA D., LE FUR Y., BARBARIA J., PELLISSIER J. - F., SABATIER J. - M., MEDINA I., COZZONE P. J. “Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.”. Annals of neurology [En ligne]. 2006. Vol. 60, n°5, p. 586-596. Disponible sur : < http://dx.doi.org/10.1002/ana.21007 > (consulté le no date)
    Résumé : OBJECTIVE: We asked whether blockade of voltage-gated K+ channel Kv1.1, whose altered axonal localization during myelin insult and remyelination may disturb nerve conduction, treats experimental autoimmune encephalomyelitis (EAE). METHODS: Electrophysiological, cell proliferation, cytokine secretion, immunohistochemical, clinical, brain magnetic resonance imaging, and spectroscopy studies assessed the effects of a selective blocker of Kv1.1, BgK-F6A, on neurons and immune cells in vitro and on EAE-induced neurological deficits and brain lesions in Lewis rats. RESULTS: BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in neurons and did not affect T-cell activation. EAE was characterized by ventriculomegaly, decreased apparent diffusion coefficient, and decreased (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Reduced apparent diffusion coefficient and impaired energy metabolism indicate astrocytic edema. Intracerebroventricularly BgK-F6A-treated rats showed attenuated clinical EAE with unexpectedly reduced ventriculomegaly and preserved apparent diffusion coefficient values and (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Thus, under BgK-F6A treatment, brain damage was dramatically reduced and energy metabolism maintained. INTERPRETATION: Kv1.1 blockade may target neurons and astrocytes, and modulate neuronal activity and neural cell volume, which may partly account for the attenuation of the neurological deficits. We propose that Kv1.1 blockade has a broad therapeutic potential in neuroinflammatory diseases (multiple sclerosis, stroke, and trauma).
    Mots-clés : Animals, Astrocytes, Blood-Brain Barrier, Brain Edema, Cell Proliferation, Cnidarian Venoms, crmbm, Encephalomyelitis, Autoimmune, Experimental, Magnetic Resonance Spectroscopy, Rats, Rats, Inbred Lew, Shaker Superfamily of Potassium Channels.

  • GIRARD N., CHAUMOITRE K., CONFORT-GOUNY S., VIOLA A., LEVRIER O. “Magnetic resonance imaging and the detection of fetal brain anomalies, injury, and physiologic adaptations.”. Current opinion in obstetrics & gynecology [En ligne]. 2006. Vol. 18, n°2, p. 164-176. Disponible sur : < http://dx.doi.org/10.1097/01.gco.0000193002.58158.07 > (consulté le no date)
    Résumé : PURPOSE OF REVIEW: Magnetic resonance imaging is playing an increasingly prominent role in depicting brain maturation, especially gyral formation that follows a temporospatial pattern, and in detecting developmental abnormalities of the cortex and other brain sectors. Knowledge of the technical advantages and limitations of in-utero magnetic resonance imaging techniques, relative to those of the postnatal period, is essential to optimize magnetic resonance sequences for early diagnosis. This includes an understanding of the changes in both brain anatomy and magnetic resonance signals that occur with an increase in gestational age. RECENT FINDINGS: Magnetic resonance imaging has evolved has an important adjunct in the diagnosis of brain malformations, particularly in the late-second or third trimester. Noxious conditions elicit more of a chronic rather than acute response in the fetal brain, which differs from that observed postnatally. Clinical applications of proton magnetic resonance spectroscopy may help elucidate fetal brain maturation and its abnormalities from a metabolic point of view. SUMMARY: Indications for fetal brain magnetic resonance imaging have increased because of improvements in magnetic resonance techniques and the ability to detect subtle changes within the cerebral parenchyma, especially in fetuses at increased risk of brain damage.
    Mots-clés : Brain, Brain Diseases, Metabolic, Inborn, crmbm, Female, Fetal Development, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Pregnancy, Prenatal Diagnosis.

  • GIRARD N., FOGLIARINI C., VIOLA A., CONFORT-GOUNY S., FUR Y. L., VIOUT P., CHAPON F., LEVRIER O., COZZONE P. “MRS of normal and impaired fetal brain development.”. European journal of radiology [En ligne]. 2006. Vol. 57, n°2, p. 217-225. Disponible sur : < http://dx.doi.org/10.1016/j.ejrad.2005.11.021 > (consulté le no date)
    Résumé : Cerebral maturation in the human fetal brain was investigated by in utero localized proton magnetic resonance spectroscopy (MRS). Spectra were acquired on a clinical MR system operating at 1.5 T. Body phased array coils (four coils) were used in combination with spinal coils (two coils). The size of the nominal volume of interest (VOI) was 4.5 cm(3) (20 mm x 15 mm x 15 mm). The MRS acquisitions were performed using a spin echo sequence at short and long echo times (TE = 30 ms and 135 ms) with a VOI located within the cerebral hemisphere at the level of the centrum semiovale. A significant reduction in myo-inositol and choline and an increase in N-acetylaspartate were observed with progressive age. The normal MR spectroscopy data reported here will help to determine whether brain metabolism is altered, especially when subtle anatomic changes are observed on conventional images. Some examples of impaired fetal brain development studied by MRS are illustrated.
    Mots-clés : Aging, Aspartic Acid, Brain, Choline, Creatine, crmbm, Female, Fetal Development, Fetus, gamma-Aminobutyric Acid, Humans, Inositol, Linear Models, Magnetic Resonance Spectroscopy, Taurine.

  • GIRARD N., GOUNY S. C., VIOLA A., LE FUR Y., VIOUT P., CHAUMOITRE K., D'ERCOLE C., GIRE C., FIGARELLA-BRANGER D., COZZONE P. J. “Assessment of normal fetal brain maturation in utero by proton magnetic resonance spectroscopy.”. Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine [En ligne]. 2006. Vol. 56, n°4, p. 768-775. Disponible sur : < http://dx.doi.org/10.1002/mrm.21017 > (consulté le no date)
    Résumé : Cerebral maturation in the normal human fetal brain was investigated by in utero localized proton MR spectroscopy ((1)H MRS). Fifty-eight subjects at 22-39 weeks of gestational age (GA) were explored. A combination of anterior body phased-array coils (four elements) and posterior spinal coils (two to three elements) was used. Four sequences were performed (point-resolved spectroscopy (PRESS) sequence with short and long TEs (30 and 135 ms), with and without water saturation). A significant reduction in myo-inositol (myo-Ins) and choline (Cho) levels, and an increase in N-acetylaspartate (NAA) and creatine (Cr) content were observed with progressing age. A new finding is the detection of NAA as early as 22 weeks of GA. This result is probably related to the fact that oligodendrocytes (whether mature or not) express NAA, as demonstrated by in vitro studies. Cho and myo-inositol were the predominant resonances from 22 to 30 weeks and decreased gradually, probably reflecting the variations in substrate needed for membrane synthesis and myelination. The normal MRS data for the second trimester of gestation (when fetal MRI is usually performed) reported here can help determine whether brain metabolism is altered or not, especially when subtle anatomic changes are observed on conventional images.
    Mots-clés : Aging, Algorithms, Aspartic Acid, Brain, Brain Chemistry, crmbm, Female, Fetal Development, Gestational Age, Humans, Linear Models, Magnetic Resonance Spectroscopy, Pregnancy.

  • PENET M. - F., LAIGLE C., FUR Y. L., CONFORT-GOUNY S., HEURTEAUX C., COZZONE P. J., VIOLA A. “In vivo characterization of brain morphometric and metabolic endophenotypes in three inbred strains of mice using magnetic resonance techniques.”. Behavior genetics [En ligne]. 2006. Vol. 36, n°5, p. 732-744. Disponible sur : < http://dx.doi.org/10.1007/s10519-006-9077-4 > (consulté le no date)
    Résumé : C57BL6J, FVB/N and 129/SvJ mice are commonly used as background strains to engineer genetic models of brain pathologies and psychiatric disorders. Magnetic resonance imaging (MRI) and spectroscopy provide alternative approaches to neuroanatomy, histology and neurohistochemistry for investigating the correlation between genes and brain neuroanatomy and neurometabolism in vivo. We used these techniques to non-invasively characterize the cerebral morphologic and metabolic endophenotypes of inbred mouse strains commonly used in neurological and behavioral research. We observed a great variability in the volume of ventricles and of structures involved in cognitive function (cerebellum and hippocampus) among these strains. In addition, distinct metabolic profiles were evidenced with variable levels of N-acetylaspartate, a neuronal marker, and of choline, a compound found in membranes and myelin. Besides, significant differences in high-energy phosphates and phospholipids were detected. Our findings demonstrate the great morphologic and metabolic heterogeneity among C57BL/ 6J, FVB/N and 129/SvJ mice. They emphasize the importance of selecting the appropriate genetic background for over-expressing or silencing a gene and provide some directions for modeling symptoms that characterize psychiatric disorders such as autism, schizophrenia and depression.
    Mots-clés : Animals, Brain, crmbm, Magnetic Resonance Imaging, Metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Phenotype.

  • SAYWELL V., VIOLA A., CONFORT-GOUNY S., LE FUR Y., VILLARD L., COZZONE P. J. “Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism.”. Biochemical and biophysical research communications [En ligne]. 2006. Vol. 340, n°3, p. 776-783. Disponible sur : < http://dx.doi.org/10.1016/j.bbrc.2005.12.080 > (consulté le no date)
    Résumé : Rett syndrome, a neurodevelopmental X-linked disorder, represents the most important genetic cause of severe mental retardation in the female population and results from a mutation in the gene encoding methyl-CpG-binding protein 2 (MECP2). We report here the first characterization of Mecp2-null mice, by in vivo magnetic resonance imaging and spectroscopy, delineating the cerebral phenotype associated with the lack of Mecp2. We performed a morphometric study that revealed a size reduction of the whole brain and of structures involved in cognitive and motor functions (cerebellum and motor cortex). Significant metabolic anomalies, including reduced N-acetylaspartate, myo-inositol, and glutamine plus glutamate, and increased choline levels were evidenced. These findings indicate that not only neuronal but also glial metabolism is affected in Mecp2-null mice. Furthermore, we uncovered an important reduction of brain ATP level, a hitherto undetected anomaly of energy metabolism that may reflect and contribute to cerebral injury and dysfunction.
    Mots-clés : Adenosine Triphosphate, Animals, Aspartic Acid, Brain, Choline, CpG Islands, crmbm, Energy Metabolism, Female, Gene Deletion, Genotype, Glutamic Acid, Glutamine, Inositol, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Methyl-CpG-Binding Protein 2, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Mutation, Neuroglia, Neurons, Phenotype.

2005

Journal Article

  • PENET M. - F., VIOLA A., CONFORT-GOUNY S., LE FUR Y., DUHAMEL G., KOBER F., IBARROLA D., IZQUIERDO M., COLTEL N., GHARIB B., GRAU G. E., COZZONE P. J. “Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema.”. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience [En ligne]. 2005. Vol. 25, n°32, p. 7352-7358. Disponible sur : < http://dx.doi.org/10.1523/JNEUROSCI.1002-05.2005 > (consulté le no date)
    Résumé : The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.
    Mots-clés : Animals, Blood-Brain Barrier, Brain, Brain Edema, Brain Ischemia, Cerebral Hemorrhage, Cerebrovascular Circulation, crmbm, Female, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Malaria, Cerebral, Mice, Mice, Inbred CBA, Neurons.

2004

Journal Article
  • BRUNEL H., GIRARD N., CONFORT-GOUNY S., VIOLA A., CHAUMOITRE K., D'ERCOLE C., FIGARELLA-BRANGER D., RAYBAUD C., COZZONE P., PANUEL M. “Fetal brain injury.”. Journal of Neuroradiology. Journal De Neuroradiologie. 2004. Vol. 31, n°2, p. 123-137.
    Résumé : Improvements in MRI techniques widen the indications for fetal brain imaging and fetal brain injury represents the third indication of fetal brain magnetic resonance imaging (MRI) after the evaluation of suspected central nervous system (CNS) malformations and ventricular dilatation. Optimal MR imaging technique is necessary in order to collect as much data as possible about the fetal brain. Diffusion images can be used routinely in addition to the standard protocol of fetal brain MRI that consists of T1 and T2 weighted images of the fetal brain. Monovoxel proton magnetic resonance spectroscopy can also be performed in utero, but this technique is still more part of research protocol than of routine clinical protocol. Fetal brain injury includes hypoxia-ischemia, congenital infections (especially toxoplasmosis and cytomegalovirus infections), brain damage due to malformation such as vascular brain malformation and heart malformation, pregnancies at risk of fetal brain damage, and even inherited metabolic diseases, especially mitochondrial diseases. MRI findings in fetal brain injury consist of acute or chronic lesions that can be seen alone or in combination. Acute response of the fetal brain is less commonly seen than the chronic response compared to the brain response encountered in the postnatal period.
    Mots-clés : Brain Injuries, Central Nervous System, crmbm, Female, Fetus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Nervous System Malformations, Pregnancy, Prenatal Diagnosis.

  • VIOLA A., NICOLI F., DENIS B., CONFORT-GOUNY S., LE FUR Y., RANJEVA J. - P., VIOUT P., COZZONE P. J. “High cerebral scyllo-inositol: a new marker of brain metabolism disturbances induced by chronic alcoholism.”. Magma (New York, N.Y.) [En ligne]. 2004. Vol. 17, n°1, p. 47-61. Disponible sur : < http://dx.doi.org/10.1007/s10334-004-0044-x > (consulté le no date)
    Résumé : Cerebral metabolic changes that concur to motor and/or cognitive disorders in actively drinking alcoholics are not well established. We tested the hypothesis that chronic alcoholics exhibit profound alterations in the cerebral metabolism of scyllo-inositol. Brain metabolism was explored in nine actively drinking and 11 recently detoxified chronic alcoholics by in vivo brain (1)H-MRS and in vitro(1)H-MRS of blood serum and cerebrospinal fluid. The cohort was composed of individuals with acute, subacute or chronic encephalopathy or without any clinical encephalopathy. Chronic alcoholism is associated with a hitherto unrecognized accumulation of brain scyllo-inositol. Our results suggest that scyllo-inositol is produced within the central nervous system and shows a diffuse but heterogenous distribution in brain where it can persist several weeks after detoxification. Its highest levels were observed in subjects with a clinically symptomatic alcohol-related encephalopathy. When detected, brain scyllo-inositol takes part in a metabolic encephalopathy since it is associated with reduced N-acetylaspartate and increased creatine. High levels of cerebral scyllo-inositol are correlated with altered glial and neuronal metabolism. Our findings suggest that the accumulation of scyllo-inositol may precede and take part in the development of symptomatic alcoholic metabolic encephalopathy.
    Mots-clés : Adult, Aged, Alcohol Drinking, Alcoholism, Biological Markers, Brain, Brain Chemistry, Brain Diseases, Metabolic, Central Nervous System, Cohort Studies, crmbm, Female, Humans, Inositol, Magnetic Resonance Spectroscopy, Male, Middle Aged, Models, Biological, Time Factors.

2002

Journal Article

  • VIOLA A., CHABROL B., NICOLI F., CONFORT-GOUNY S., VIOUT P., COZZONE P. J. “Magnetic resonance spectroscopy study of glycine pathways in nonketotic hyperglycinemia.”. Pediatric research [En ligne]. 2002. Vol. 52, n°2, p. 292-300. Disponible sur : < http://dx.doi.org/10.1203/00006450-200208000-00024 > (consulté le no date)
    Résumé : Nonketotic hyperglycinemia is a life-threatening disorder in neonates characterized by a deficiency of the glycine cleavage system. We report on four cases of the neonatal form of the disease, which were investigated by in vitro(1)H magnetic resonance spectroscopy of blood and cerebrospinal fluid, and in vivo(1)H magnetic resonance spectroscopy of brain. The existence of glycine disposal pathways leading to an increase in lactate in fluids and creatine in fluids and brain was demonstrated. This is the first observation of elevated creatine in brain in nonketotic hyperglycinemia. A recurrent decrease of glutamine and citrate was observed in cerebrospinal fluid, which might be related to abnormal glutamine metabolism in brain. Finally, the cerebral N-acetylaspartate to myo-inositol-glycine ratio was identified as a prognostic indicator of the disease.
    Mots-clés : Aspartic Acid, Brain, Child, Preschool, Dextromethorphan, Excitatory Amino Acid Antagonists, Female, Glycine, Humans, Hyperglycinemia, Nonketotic, Infant, Inositol, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Prognosis, Sodium Benzoate.
  • VIOLA A., CONFORT-GOUNY S., RANJEVA J. - P., CHABROL B., RAYBAUD C., VINTILA F., COZZONE P. J. “MR imaging and MR spectroscopy in rhizomelic chondrodysplasia punctata.”. AJNR. American journal of neuroradiology. 2002. Vol. 23, n°3, p. 480-483.
    Résumé : A case of rhizomelic chondrodysplasia punctata was investigated with MR imaging of the brain and hydrogen-1 MR spectroscopy of the brain and blood. Areas with abnormal signal hyperintensity on T2-weighted images or hypointensity on T1-weighted images were detected in the subcortical white matter. MR spectroscopy of the brain showed that normal-appearing white matter was characterized by increased levels of mobile lipids and myo-inositol, reduced levels of choline, and the presence of acetate. The importance of these metabolic anomalies is correlated to the deficiency in plasmalogen biosynthesis.
    Mots-clés : Acyltransferases, Brain, Chondrodysplasia Punctata, Rhizomelic, Humans, Infant, Newborn, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Plasmalogens.

2001

Journal Article
  • VIOLA A., NICOLI F., CONFORT-GOUNY S., LE FUR Y., RANJEVA J. P., COZZONE P. J. “[Applications of magnetic resonance spectrometry (MRS) in the study of metabolic disturbances affecting the brain in alcoholism].”. Pathologie-biologie. 2001. Vol. 49, n°9, p. 718-725.
    Résumé : The purpose of this article is to provide an overview of the current applications of magnetic resonance spectroscopy (MRS) to the investigation of cerebral metabolism in alcoholic patients. The specific metabolic changes associated with the intoxication process (tolerance, dependance), abstinence and alcohol-related diseases (alcoholic encephalopathy, cirrhosis, Gayet-Wernicke's encephalopathy, Marchiafava-Bignami syndrome) are described.
    Mots-clés : Alcohol-Induced Disorders, Nervous System, Alcoholism, Animals, Brain, Brain Diseases, Disease Models, Animal, HIV Infections, Humans, Magnetic Resonance Spectroscopy.
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