Дисертації з теми "Cerveau – Marqueurs biologiques"
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Mani, Meenakshi. "Quantitative analysis of open curves in brain imaging : applications to white matter fibres and sulci." Rennes 1, 2011. http://www.theses.fr/2011REN1S026.
Повний текст джерелаCette thèse se propose d'étudier comment les caractéristiques des courbes ouvertes peuvent être exploitées afin d'analyser quantitativement les sillons corticaux et les faisceaux de matière blanche. Les quatre caractéristiques d'une courbe ouverte--forme, taille, orientation et position--ont des propriétés différentes, si bien que l'approche usuelle est de traiter chacune séparément à l'aide d'une métrique ad hoc. Nous introduisons un cadre riemannien adapté dans lequel il est possible de fusionner les espaces de caractéristiques afin d'analyser conjointement plusieurs caractéristiques. Cette approche permet d'apparier et de comparer des courbes suivant des distances géodésiques. Les correspondances entre courbes sont établies automatiquement en utilisant une métrique élastique. Dans cette thèse, nous validerons les métriques introduites et nous montrerons leurs applications pratiques, entre autres dans le cadre de plusieurs problèmes cliniques importants. Dans un premier temps, nous étudierons spécifiquement les fibres du corps calleux, afin de montrer comment le choix de la métrique influe sur le résultat du clustering. Nous proposons ensuite des outils permettant de calculer des statistiques sommaires sur les courbes, ce qui est un premier pas vers leur analyse statistique. Nous représentons les groupes de faisceaux par la moyenne et la variance de leurs principales caractéristiques, ce qui permet de réduire le volume des données dans l'analyse des faisceaux de matière blanche. Ensuite, nous présentons des méthodes permettant de détecter les changements morphologiques et les atteintes de la matière blanche. Quant aux sillons corticaux, nous nous intéressons au problème de leur labellisation
Etcheverry, Amandine. "Étude du méthylome des glioblastomes de l'adulte." Rennes 1, 2012. http://www.theses.fr/2012REN1S077.
Повний текст джерелаGlioblastoma, the most common and most aggressive malignant primary brain tumour in adults, is characterised by a poor prognosis. This tumour is heterogeneous in terms of molecular alterations, prognosis, and therapeutic response. Despite this heterogeneity, few biomarkers have been associated with patient survival. DNA methylation plays a major role in orchestrating gene expression. Alterations in DNA methylation are common in cancers. They represent promising therapeutic targets and excellent biomarkers for use in clinical oncology. In this context, the research conducted during this thesis has led to refine the molecular characterization of glioblastoma by identifying genes whose expression is regulated by epigenetic mechanisms and identify epigenetic biomarkers that improve the molecular stratification of glioblastoma patients. These results open numerous perspectives in both fundamental and translational research. Our efforts are focused on the validation of the identified epigenetic biomarkers and on their functional study
Tayrac, Marie de. "Analyse génomique et transcriptomique des glioblastomes multiformes." Rennes 1, 2009. http://www.theses.fr/2009REN1B126.
Повний текст джерелаGlioblastomas are among the most devastating of human nervous system tumors. Advances in Functional Genomic and particularly in the development of high-throughput technologies - such as microarrays -, allow the analysis of both DNA alterations and gene expression changes on a genome-wide scale. They make possible the identification of molecules involved in tumor initiations, development and progression as well as the discovery of useful biomarkers to improve patient care. The present research takes place in such a context. Our initial objective was to provide genomic and transcriptomic characterization of glioblastomas. We had specificially to identify the DNA alterations that directly drives the disease process - i. E. Alterations that may exert their tumor-promoting effect by modifying the expression or function of distinct genes, so as to deregulate growth factor signaling and survivor pathways. Completion of this project has firstly required a methodological development to allow the simultaneous analysis of large scale data sets coming from different "-omic" areas. Glioblastoma genome and transcriptome profiling were obtained and combined to provide a robust molecular signature characterizing these tumors. We have also expanded our work to search for biomarkers for diagnosis and prognosis of patient with malignant gliomas. This thesis has been driven by a multidisciplinary approach - such an approach being necessary to the analysis of high throughput studies. We therefore wished to provide a substantial introduction, which would help everyone - clinicians, biologists, and statisticians - to get the fundamentals required to understand our work
Abraham, Alexandre. "Apprentissage d'atlas fonctionnel du cerveau modélisant la variabilité inter-individuelle." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS159/document.
Повний текст джерелаRecent studies have shown that resting-state spontaneous brain activity unveils intrinsic cerebral functioning and complete information brought by prototype task study. From these signals, we will set up a functional atlas of the brain, along with an across-subject variability model. The novelty of our approach lies in the integration of neuroscientific priors and inter-individual variability in a probabilistic description of the rest activity. These models will be applied to large datasets. This variability, ignored until now, may lead to learning of fuzzy atlases, thus limited in term of resolution. This program yields both numerical and algorithmic challenges because of the data volume but also because of the complexity of modelisation
Lavoie, Joëlle. "Exploration des origines des anomalies de l'électrorétinogramme chez les patients atteints de maladies psychiatriques : Des biomarqueurs potentiels des maladies du cerveau." Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30752/30752.pdf.
Повний текст джерелаOne of the major obstacles in psychiatry is the difficult access to the functioning brain to better understand the biological underpinning of brain disorders. There is a need to develop new approaches to study the neurological functions indirectly. Since the retina is part of the central nervous system, it had been suggested that retinal functions, as measured with the electroretinogram (ERG), may reflect the central dysfunctions reported in psychiatric disorders. In fact, several ERG anomalies, which may serve as biomarkers, have been observed in people with or at risk of psychiatric disorders, such as seasonal affective disorder (SAD) and schizophrenia. However, the origins of these ERG anomalies remain elusive and the goal of this thesis is to explore the potential molecular underpinning of these ERG deficits with animal models of psychiatric disorders or the use of a pharmacological agent. Because of their well-described involvement in psychiatric disorders, the targeted molecules of the experiments presented in this thesis are melatonin, central dopamine, central serotonin and glycogen synthase kinase-3 (GSK3). The first study demonstrates that a dysfunction in melatonin secretion may partially be involved in the ERG anomalies observed in people with SAD. The second study is a complement of the first one and reports that impairments in central serotonin and central dopamine neurotransmission are more likely to be involved in the ERG anomalies observed in patients with SAD than changes in the retinal bioavailability of dopamine receptors D1R and D2R. A multifactorial model of the ERG anomalies in people with SAD has been proposed according to the findings of these two previous studies. Moreover, the third study demonstrates that GSK3 overexpression, which is a risk factor for schizophrenia and bipolar disorder, replicates the ERG anomaly reported in offspring at high genetic risk for these disorders. Finally, the fourth study demonstrates that GSK3 plays an important role in regulating the biological clock. Overall, this thesis suggests that ERG measurements represent a useful tool in psychiatric research.
Dabadie, Henry. "Contribution à l'étude des trace aminés à partir d'une détection immunocytochimique au niveau du cerveau de rat." Bordeaux 2, 1993. http://www.theses.fr/1993BOR28252.
Повний текст джерелаMercier, Éric. "La valeur pronostique de la protéine S-100B et de l'énolase neurone-spécifique suivant un traumatisme craniocérébral modéré ou grave : revues systématiques et méta-analyses." Master's thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/26963.
Повний текст джерелаThe main objective of this study is to determine the prognostic value of S-100ß protein and neuron-specific enolase (NSE) following a moderate or severe traumatic brain injury (TBI). Two systematic reviews and meta-analysis were performed to find the studies having evaluated the link between a level of those biomarkers and the mortality or the Glasgow outcome scale (GOS). Of the 9228 citations, 41 and 26 studies were finally included respectively for S-100ß protein and NSE. We observed a significant association between blood levels of S-100ß protein and NSE and an unfavorable outcome such as the mortality or the GOS ≤ 3. A 100% specificity serum level threshold for mortality was between 1.38 to 10.50 µg/L for the S-100ß protein. The association showed consistent results despite the presence of significant extracranial injuries.
Brochier, Camille. "Analyse des transcriptomes du cerveau de souris : mise en évidence de patrons régionaux d'expression conservés chez l'homme et altérés dans des modèles de maladies neurodégénératives." Phd thesis, Université Paris Sud - Paris XI, 2007. http://tel.archives-ouvertes.fr/tel-00361207.
Повний текст джерелаBinter, Anne-Claire. "Effets de l’exposition prénatale aux neurotoxiques sur le fonctionnement du cerveau de l’enfant évalué par imagerie cérébrale." Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1B052.
Повний текст джерелаAbstract: The vulnerability of the developing brain to its environment is well known in the literature. Some cognitive and behavioral alterations observed after prenatal exposure to glycol ethers and organophosphate insecticide suggest a possible impairment of executive functions. In particular, we suspected an alteration of the inhibitory control, a predictor of academic performance or tendency to risky behaviors in adulthood. Therefore, better understanding these effects appears as a key issue of public health. We aimed at investigating the effects of prenatal exposure to glycol ethers and organophosphate insecticides on the child’s brain function evaluated by cerebral imaging. This work is based on the data of the mother-child PELAGIE cohort. The longitudinal follow-up allowed to measure with biomarkers the exposure to neurotoxicants during pregnancy. We used a Go/No-Go task and functional MRI to assess the inhibitory control and its neural mechanisms in children aged 10-12 years. Our results suggest that inhibitory control may be altered after prenatal exposure to these contaminants. However, some of our findings about glycol ethers were unexpected regarding existing literature and showed little consistency, preventing us to conclude to a significant effect on the developing brain. Then, we suggested that the frontal cortex, involved in inhibition network, may be a specific target of organophosphates
Serrière, Sophie. "Recherche de biomarqueurs précoces par SRM 1 H haute résolution dans l'hypoxie ischémie cérébrale néonatale et dans l'inflammation materno-foetale." Tours, 2005. http://www.theses.fr/2005TOUR3308.
Повний текст джерелаA metabonomic approach using high resolution resonance magnetic spectroscopy was investigated on newborn (piglet model of cerebral hypoxia ischemia) and maternal (rat model of maternofetal inflammation induced by E Coli lipopolysaccharid injections) biological fluids. The aim of this study was to evidence an early biomarker of these two pathologies. Neither in the urine and nor in the cerebrospinal fluid of hypoxic ischemic animals, specifi biomarkers of the pathology were evidenced. Metabonomic studies combined with multivaried analysis on the maternal blood plasma and on the amniotic fluid of inflammation-induced animals at day eighteen and nineteen of gestation had evidenced some specific biomarkers. In addition, inflammation impact was demonstrated on pregnancy outcome, on the mean number of newborn per litter and on the newborn growth during the fourteen's days of life
Smine, Selima. "Obésité induite par un régime riche en lipides (HFD) et effet protecteur d'un extrait polyphénolique de raisin (GSSE) : approche protéomique." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR111/document.
Повний текст джерелаThe effects of GSSE (Grape seed and skin extract) extracted from grapes particularly rich in antioxidants have been studied to prevent metabolic and cardiovascular disorders related to obesity. Obesity is characterized by an ectopic accumulation of fat in non-adipose tissues such as the brain. This cerebral lipotoxicity induces chronic inflammation of the brain. In this work, using quantitative proteomic analysis, biochemical and bio-informatic tools allows us to identify actors of metabolic and biological pathways that were disregulated in brain of experimentally-induced obese rats and corrected by GSSE treatment. While our data are consistent with previous findings of obesity-induced brain lipotoxicity, such as enhancement of proteins belonging to the OXPHOS and calcium pathways, they also unveiled novel pathways including the up-regulation of HIF-signaling pathway in HFD brains. In the same context, GSSE abrogated HFD-induced signaling pathway elevation either by modulating several proteins or by inducing some others that were not affected by HFD
Mendez, Gomez Juan Luis. "Biomarqueurs rétiniens de la maladie d'Alzheimer et du vieillissement cérébral." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0370/document.
Повний текст джерелаThe eye and central nervous system (CNS) have a common embryological origin, and easily observable retinal structures may reflect brain damage. The primary objective of this thesis was to analyze the relationship between retinal disorders and clinical (cognitive decline, dementia) and para-clinical (brain imaging) brain aging manifestations. Two types of retinal "biomarkers" were analyzed: the retinal nerve fiber layer (RNFL) and vascular structures. The data used come from the population-based cohort 3-Cities Alienor. We have shown that subjects with reduced RNFL thickness (measured by spectral-domain optical coherence tomography, SD-OCT) showed a reduced episodic memory score (cognitive function that is principally affected in Alzheimer's disease, AD) after 2 years of follow-up; over this short period of time no association with dementia risk was found. A reduced RNFL thickness was also associated with altered MRI parameters in visual pathways and in limbic system regions, which are particularly vulnerable in AD. Finally we have shown that reduced vascular choroid layer thickness was associated with larger white matter hyperintensities volumes. Vascular and neurodegenerative disease processes are associated with brain aging. Thus, alterations in the CNS by AD and brain aging could be reflected in the retina. Other research is still needed before considering the retina as a potential biomarker of brain aging
Pierrefeu, Amicie de. "Apprentissage automatique avec parcimonie structurée : application au phénotypage basé sur la neuroimagerie pour la schizophrénie." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS329/document.
Повний текст джерелаSchizophrenia is a disabling chronic mental disorder characterized by various symptoms such as hallucinations, delusions as well as impairments in high-order cognitive functions. Over the years, Magnetic Resonance Imaging (MRI) has been increasingly used to gain insights on the structural and functional abnormalities inherent to the disorder. Recent progress in machine learning together with the availability of large datasets now pave the way to capture complex relationships to make inferences at an individual level in the perspective of computer-aided diagnosis/prognosis or biomarkers discovery. Given the limitations of state-of-the-art sparse algorithms to produce stable and interpretable predictive signatures, we have pushed forward the regularization approaches extending classical algorithms with structural constraints issued from the known biological structure (spatial structure of the brain) in order to force the solution to adhere to biological priors, producing more plausible interpretable solutions. Such structured sparsity constraints have been leveraged to identify first, a neuroanatomical signature of schizophrenia and second a neuroimaging functional signature of hallucinations in patients with schizophrenia. Additionally, we also extended the popular PCA (Principal Component Analysis) with spatial regularization to identify interpretable patterns of the neuroimaging variability in either functional or anatomical meshes of the cortical surface
Genovese, Guglielmo. "Evaluation of microstructural alterations in the human brain and in experimental models with diffusion-weighted magnetic resonance spectroscopy." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS545.
Повний текст джерелаDiffusion-weighted magnetic resonance spectroscopy (DW-MRS) is a unique tool to investigate brain microstructure in a cell-specific manner, while neglecting phenomena related to the extracellular environment. In this thesis, we studied DW-MRS in several complementary ways in order to be able to apply this technique in later clinical studies: optimization of the acquisition pipeline and data analysis, reproducibility of the diffusion measures, and histological validation of the DW-MRS metrics as potential useful markers of brain diseases-related microstructural alterations. The thesis is composed of three parts. In the first part, we propose an optimization of the acquisition and of the post-processing procedures for single-voxel DW-MRS experiments in humans, and an evaluation of the feasibility of a DW-semi-LASER sequence for clinical studies at 3 T. Power calculations for the metabolite diffusion measures were reported in order to provide useful information for designing case-control studies in patients with brain diseases. In the second part, we focused on validating DW-MRS metrics using histological measures in two different mouse models of myelinopathy. A strong correlation was found between mIns diffusivity and the astrocyte area fraction confirming the hypothesis that mIns diffusivity can be used as a marker of astrocyte hypertrophy during the inflammatory process. In the last part, we studied the longitudinal evolution of axonal and glial alterations after ischemic stroke in the human brain. We observed the presence of inflammation due to glial reactivity about one month after ischemic stroke and astrocytic reactivity up to about three months after the ischemic stroke
Malherbe, Caroline. "Imagerie des faisceaux de fibres et des réseaux fonctionnels du cerveau : application à l'étude du syndrome de Gilles de la Tourette." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00980572.
Повний текст джерелаHinfray, Nathalie. "Etude de l'expression des cytochromes P 450 aromatases commr marqueurs biologiques d'une perturbation endocrinienne chez le poisson." Metz, 2006. http://docnum.univ-lorraine.fr/public/UPV-M/Theses/2006/Hinfray.Nathalie.SMZ0621.pdf.
Повний текст джерелаThe objective of this work was to study the effects of endocrine disrupting chernicals (EDCs) on brain and gonadal P45Oaromatase in fish in order to determine to which extent these genes or their products could be used as biomarkers of endocrine disruption in fish. We first developed methods to measure cypl9a and cypl9b mRNA and protein levels, as well as activity of brain and gonadal aromatase in zebrafish (Danio rerio). These methods allowed us to obtain relevant and original data on the expression of aromatases in this species. Next, we assessed the effects of several environmental pollutants and characterized the inhibitory potency of several pesticides using an in vitro assay based on brain and gonadal microsomal aromatase fiom rainbow trout (Oncorhynchus mykiss). Clotrimazole, an imidazole fùngicide used as a pharmaceutical, was found to be the most active substance among the tested pesticides. In vivo, we observed that various substances can perturb brain and gonadal aromatase and elicit tissue-specific responses. While androstadrienedione (a steroidal inhibitor of aromatase) inhibited aromatase activity in both brain and gonads without affecting cypl9 expression, the in vivo action of clotrimazole (characterized as an aromatase inhibitor in vitro) was more complex. The effects of this molecule differed depending on the target tissue and the concentration used for exposure. Moreover, the effects observed on the mRNA levels did not allow to predict the effects on the aromatase activity. Finally, we showed that some xenoestrogens are able to inhibit ovarian aromatase gene expression and at the same time to induce brain aromatase at the gene and protein level through an estrogen receptor (ER)-dependent mechanism. This demonstrates that measurement of cypl9b induction is a relevant biomarker of exposure to estrogenic compounds. Taken together, Our work provides new and relevant data concerning the effects and mechanisms of action of EDCs in fish, especially in female individuals. However, to determine the physiological and reproductive consequences of aromatase perturbation, M e r research is needed. Such knowledge is critical for establishing the use of these biomarkers in risk assessrnent of EDCs
Tachrount, Mohamed. "Spectroscopie proton à 3T : Imagerie spectroscopique volumétrique spirale à TE court." Grenoble 1, 2009. http://www.theses.fr/2009GRE10339.
Повний текст джерелаProton magnetic resonance chemical shift imaging (CSI) at short time (TE) in vivo allows characterization of the spatial distribution of strongly J-coupled and short T2 biomarkers relevant to healthy or pathologic metabolism. We have developed a volumetric CSI technique for human brain studies at 3 Tesla in an experiment time compatible with patient examination. Pulse sequence modules for selection of the volume of interest (PRESS and semi-LASER), and for suppression of water and outer volume signals were implemented and optimized. The use of spiral K-space trajectories allowed acquisition speed-up by simultaneous encoding of spatial and spectral dimensions. Techniques of calibration and optimisation of the effective trajectory were developed, as well as an algorithm for reconstruction of 2 or 3 D spatial – 1 D spectral data sets. The method was validated in vivo on human brain with TEs of 17 ms (PRESS) or 32 ms (semi-LASER), on healthy subjects. Good saturation of subcutaneous lipids was obtained. Semi-LASER, by its use of adiabatic RF pulses, brought both sharper spatial selection profiles less sensitive to B1 inhomogeneity, and reduced chemical shift displacement errors. Using the measured trajectory for data reconstruction reduced artefacts associated with gradient hardware imperfections. NAA, Creatine, Choline, myo-Inositol and Glutamate/Glutamine were significantly quantified both with PRESS and semi-LASER. Clinical application of short TE volumetric spiral CSI at 3T can be considered
Tabouret, Emeline. "Glioblastome et angiogenèse : profils évolutifs, interaction avec l'invasivité et implications thérapeutiques." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5012/document.
Повний текст джерелаGlioblastomas are the most frequent and aggressive primary brain tumors for adult. They are characterized by a high angiogenesis leading to the evaluation of the bevacizumab. Our aim was to identify potential predictive biomarkers of bevacizumab activity and to analyze the evolutive profile of the angiogenic factors during the disease. If no clinical factor allows the identification of patient subgroup benefiting of bevacizumab, MMP2 and MMP9 plasma level at baseline were correlated to response, progression-free survival and overall survival of patients with recurrent high grade glioma treated by bevacizumab. Moreover, plasma levels of these markers change during treatment and significantly varied at the time of progression. We observed similar results for patients with inflammatory breast cancer treated with neoadjuvant bevacizumab, reinforcing the potential value of these prebiomarkers. In tumor tissue, while we did not observed changes in MMP2/MMP9 expression between the initial diagnosis and the recurrence post radio-chemotherapy, we observed a modification of the expression of angiogenic factors with a potential switch from the VEGFR2-HIF1α to the CXCL12-CXCR4 pathway. These results lead to new perspectives in angiogenic modulation and glioblastoma treatment
Charroud, Céline. "Biomarqueurs d'imagerie fonctionnelle de la mémoire de travail au cours du vieillissement cérébral normal." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS006/document.
Повний текст джерелаNormal brain aging is characterized by a progressive decline in information processing ability in particular in the system of working memory. Therefore, it is essential to examine neural substrates underlying the working memory system which can be assessed by functional magnetic resonance imaging (fMRI). The aim of our work is to explore, in a large cohort of healthy elderly individuals, reorganizations in the networks in relation to (i) increase task load during a DIR (delayed item recognition) task, (ii) age during increase DIR task load and (iii) the performance in the DIR task during a resting state. Three hundred and eighty elderly participants (82 years, 56% women) from the Three-City cohort in Montpellier have been selected to perform an fMRI exam including a DIR task and a resting state. DIR task consisted of three phases: (i) stimulation – presentation of one, three or six letters - (ii) retention - blank screen to hold the stimulus items in mind - and (iii) probe - after the presentation of a target letter, the participant indicates whether or not this probe matched a letter in the study array. In the first work, using a covariance analysis, we observed, when the difficulty of the DIR task increases, simultaneously increased activation in salience and central executive networks during three phases separately of the DIR task and decreased activation in DMN during stimulation phase and in limbic regions and deep grey nuclei during retention phase. It may be hypothesized that salience and central executive networks interact in a complex way with DMN and limbic regions and deep grey nuclei. In the second work, age effects on load-dependent increases activations of the task were explored. Reduced activation in the left parietal lobe was identified in very old individuals compared to young old individuals during the stimulation phase suggesting an involvement of posterior–anterior shift with increasing age. In the third work, networks implicated in working memory (central executive, salience and the default mode networks) were highlighted by independent component analysis during the resting state. Our findings have confirmed that the functional connectivity and performance are related by: (i) a decreased in the both salience and the default mode networks and (ii) an increased in the central executive network. We can suggest that the decreased functional connectivity within the salience and the default mode networks could be due attentional and memory processes alterations and/or altered motivation. The increased functional connectivity within the central executive network could be related to compensatory mechanisms meanwhile elders would perform more poorly. All of these studies indicate that brain reorganizations of neural networks (salience, central executive and default mode) underlying working memory in normal brain aging