Дисертації з теми "Imagerie en biologie – Expérimentation animale"
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Rucher, Guillaume. "Imagerie moléculaire des lésions d'athérosclérose vasculaires et valvulaires chez la souris." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMC401/document.
Повний текст джерелаAtherosclerosis lesions are a leading cause of cardiovascular events. Atherosclerosis is a chronic inflammatory disease including complex molecular and cellular mechanisms. Mineralization process within the atherosclerosis lesions is a key feature of the disease development. Using a mouse model of accelerated atherosclerosis and imaging optimisation study, we showed the feasability of sodium fluoride positron emission tomography combined to magnetic resonance imaging to assess molecular activity in a mouse model of accelerated atherosclerosis. We showed that uremic animals had an early and sustained mineralization activity associated to an advanced inflammatory state. Furthermore, we developped a new mouse model of calcified aortic stenosis using targeted radiation exposure
Guillemant, Marie. "Development of a three-photon microscope for awake and behaving non-human primates." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL025.
Повний текст джерелаMulti-photon microscopy has become a standard technique to study the structural and functional activity in mice but it faces obstacles to be applied in larger animals. It would be particularly advantageous to be able to apply it to macaque monkeys, as they are the animal model of choice to understand the neural mechanisms of high-level cognitive functions such as selective attention, working memory and consciousness. One of the main limiting factors for imaging in larger animals is the dura mater. This tough and opaque layer of tissue protects the brain but is so thick in larger animals that it obstructs imaging. It is therefore commonly removed but this leads to a highly invasive and unstable preparation. The main aim of the current work is to investigate the possibility to record functional activity from the cortex of the rhesus macaque monkey through the natural dura.A multi-photon microscopy setup has been designed with a two-photon and a three-photon microscopy optical paths to record from awake macaque monkeys. The repetition rate of the laser is 2MHz which allows a maximum imaging depth inside the cortex of 520µm at 960nm and 715µm at 1300nm with an additional 120µm-thick layer of dura mater at the surface. Resonance-galvo scanning is used to allow a maximal frame rate of 15.6Hz at a field of view of 620x630µm². In addition to the setup, surgical implants have been developed for long-term and awake imaging.Using an ex vivo study of dura mater from a macaque monkey, the induced optical aberrations are studied by measuring the decrease in spatial resolution of the setup for a varying thickness of dura mater. This reveals that it has no significant impact on the spatial resolution for a thickness up to 150µm at 1300nm. The effective attenuation length of the dura mater is estimated to be 56.5±10.1µm at 960nm and 80.7±5.3µm at 1300nm. These measurements are used to model the maximum imaging depth that can be reached according to the repetition rate of the laser and the thickness of the dura.This model is adjusted and validated using in vivo data from two non-human primates. The effective attenuation length of the natural dura mater and of a regrowth of tissue following a durectomy (called a 'neomembrane') are investigated. Functional recordings have been performed in mice and preprocessed using Suite2P. Viral injection parameters have been tested in three macaque monkeys and we have so far recorded the in vivo structural and functional activity of neurons in one. Finally, the comparison between the use of two- and three-photon microscopy to study non-human primates is discussed. In conclusion, we have set up and optimized a multi-photon microscope for long-term awake imaging of the cortex of non-human primates and shown that it was possible to record down to over 700µm into the cortex (which corresponds to the layers L2/L3) while imaging through the natural dura mater or a neomembrane
Monteil, Jacques. "Imagerie au 18-FDG avec un tomographe d’émission de positons par détection de coïncidences (TEDC) : optimisation pour l’oncologie expérimentale animale." Limoges, 2004. http://www.unilim.fr/theses-doctorat/2004LIMO310D/html/index-frames.html.
Повний текст джерелаTropres, Irène. "Imagerie RMN de la microvascularisation cérébrale chez le rat : applications." Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE19012.
Повний текст джерелаBreton, Élodie. "Applications précliniques de l'IRM à bas champ et sa place dans un contexte multimodal microTEMP et microTDM." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/public/theses_doctorat/2007/BRETON_Elodie_2007.pdf.
Повний текст джерелаIn vivo preclinical imaging in small animals offers a unique insight in physiopathological processes. This PhD thesis is a study of the role that 0. 1T low field MRI could play in preclinical imaging considering its economical and technical characteristics. The specificities of preclinical imaging are first presented, then the technical adaptations developed for in vivo small animal imaging using 0. 1T MRI are detailed. These technical choices allow to obtain quantitative results using 0. 1T MRI in various in vivo imaging studies: anatomical (longitudinal follow-up of tumor growth), functional (triggered cardiac dynamic) and motion-sensitizing gradients (MRE). In a multimodal context, the complementarity of imaging techniques is shown through the simple and original conception of a dual SPECT/low field MRI modality, and the use of microCT in some specific soft tissues studies
Vazeille, Emilie. "Etude de la protéolyse protéasome-dépendante et de l'apoptose mitochondriale pendant l'atrophie et la récupération musculaire : rôle du curcumin." Clermont-Ferrand 1, 2009. http://www.theses.fr/2009CLF1MM02.
Повний текст джерелаUncontrolled and sustained muscle wasting observed in various catabolic situations (e. G. Aging, cancers, AIDS) may reduce the response to therapies and the efficiency of immune system, thus increasing morbidity and mortality. The subsequent weakness impairs human movement and ultimately can lead bed-rest, which is a worsening factor of muscle atrophy. Proteolytic and apoptotic pathways play a crucial role in the establishment of muscle atrophy. However, their respective role during recovery periods is not clearly defined. The purpose of my Ph. D. Thesis was to better characterize these mechanisms during muscle loss and the recovery following immobilization. Adult rats were subjected to unilateral hindlimb casting for 8 days and allowed to recover up to 40 days. The controlateral leg served as control in all experiments. We showed that the mitochondria-associated apoptotic pathway was up-regulated concomitantly to the ubiquitin(ub)-proteasome-dependent system during immobilization induced-muscle atrophy. We also demonstrate that these pathways are sequentially normalized during skeletal muscle recovery. Indeed, ub-proteasome-dependent proteolysis is normalized when muscle atrophy stabilized whereas the mitochondria-associated apoptotic pathway is later sequentially down-regulated and normalized when muscle mass increased. Finally, the daily administration of curcumin, which exhibit anti-oxydant and anti-inflammatory properties, speeded up muscle mass recovery by furthering the normalization of these two processes. In conclusion, my Ph. D. Thesis work demonstrated the crucial role of the mitochondria-associated apoptotic pathway during the casting induced-muscle atrophy. It further demonstrated that the ub-proteasome-dependent proteolytic and the mitochondria-associated apoptotic pathways are regulated according to different kinetics during muscle recovery. Finally, the study of the beneficial effects of curcumin indicated that nutritional strategies adapted to different stages of muscle recovery are conceivable to improve muscle mass accretion
Le, Bars Emmanuelle. "Application des techniques de spectroscopie et d'imagerie par résonance magnétique in "vivo" : étude des effets métaboliques cérébraux induits au cours d'une hypoxémie modérée et d'une ischémie focale chez le rat." Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE19002.
Повний текст джерелаJoubert, Michaël. "Diabète et remodelage cardiaque : approches physiopathologiques et mécanistiques." Caen, 2016. http://www.theses.fr/2016CAEN3164.
Повний текст джерелаType 2 diabetes is growing epidemic worldwide and this metabolic disease is associated with increased cardiovascular morbidity and mortality. Long term hyperglycemia is involved in the development of atherosclerosis, especially in coronary arteries, but diabetes also causes direct myocardial abnormalities (diabetic cardiomyopathy). The mechanisms involved in the deleterious effects of diabetes on the heart are not yet fully explained. Using a rodent models with streptozotocin-induced diabetes, we explored the impact of diabetes, especially glycemic variability, on ischemia-reperfusion injury and the early impact of diabetes on the occurrence of diabetic cardiomyopathy. In addition, using a mouse model of lipo-atrophic diabetes, we also studied the mechanisms involved in diabetic cardiomyopathy and in particular the consequences of glucotoxicity. Parallel to this work, a methodological study evaluated the reproducibility of cardiac MRI in rodents, the main exploration tool for our work
Guignard, Léo. "Analyse quantitative de la morphogenèse animale : de l'imagerie laser haut-débit à l'embryon virtuel chez les ascidies." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS048/document.
Повний текст джерелаAscidian embryos develop with stereotyped and evolutionarily conserved invariant cell lineages to produce in a few hours or days tadpole larvae with a small number of cells. They thus provide an attractive framework to describe with cellular resolution the developmental program of a whole organism. During my PhD, I developed a quantitative approach to describe the evolution of embryonic morphologies during the development of the ascidian Phallusia mammillata. I then used this approach to systematically characterize in detail the logic of cell fate induction events. To quantitatively characterize cell behaviors during embryogenesis, we used multi-angle light-sheet microscopy to image with high spatio-temporal resolution entire live embryos with fluorescently labeled plasma membranes. To extract biological information from this imaging dataset, I then developed a conceptually novel automated method for 4D cell segmentation, ASTEC. Applied to a Phallusia mammillata embryo imaged for 6 hours between the 64-cell and the initial tailbud stages, this method allows the accurate tracking and shape analysis of 1030 cells across 640 cell divisions. The resulting 4D digital embryo can be formalized as a dynamic graph, in which cells are represented by nodes, linked within a time point by edges that represent their spatial neighborhood, and between time points by temporal edges describing cell lineages.Based on this quantitative digital representation, we systematically identified cell fate specification events up to the late gastrula stage. Computational simulations revealed that remarkably simple rules integrating measured cell-cell contact areas with boolean spatio-temporal expression data for extracellular signalling molecules are sufficient to explain most early cell inductions. This work suggests that in embryos establishing precise stereotyped contacts between neighboring cells, the genomic constraints for precise gene expression levels are relaxed, thereby allowing rapid genome evolution
Lemasson, Benjamin. "Evaluation de l'IRM multiparamétrique comme indicateur de l'effet de thérapies anti-angiogéniques sur des modèles de gliomes implantés chez le rat." Phd thesis, Université de Grenoble, 2010. http://tel.archives-ouvertes.fr/tel-00908915.
Повний текст джерелаTsiakaka, Olivier. "Contribution à la réalisation d’un dispositif multimodal pour l’imagerie de la moelle épinière." Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS359.
Повний текст джерелаThis thesis focuses on the instrumentation of the SC, through the development of an experimental device. It uses the Diffuse Optical Imaging (DOI) technique to quantify the local variations of blood flow. For this purpose, several prototypes were designed and used during animal experiments. An optical characterisation was performed on SC samples, ex vivo and in vivo. We built up on this information, representing a first for the state of art, to establish guidelines for the development of the embedded device in the hostile biological environment. The feasability of the functional monitoring with DOI in the big animal (FBM pig) is now proven. The design methodology is addressed in order to highlight the interdependances between the measurement and the system. The results are very promising. They open a new path of exploration, complementary to the ones in everyday medical routine. In fine, this approach will be able to give quantitative indicators for the evaluation and the care of medullar pathologies. Destined for hospital praticians first, several purposes may be drawn from this device ranging from orthopedic to vascular surgeries for pets and humans. Researchers may also benefit from such a tool that would help them understand better the SC and its independance regarding the brain
Dillenseger, Jean-Philippe. "Imagerie préclinique multimodale chez le petit animal : qualification des instruments et des méthodes (IRM, µTDM et µTEMP)." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAD026/document.
Повний текст джерелаPreclinical imaging is mostly performed on mouse animal models (61%). It is a necessary step in preclinical research, in compliance the first two recommendations of the 3Rs rules (reduction, refinement and replacement). In order to give a biological significance to measurements extracted from in vivo-acquired mouse images, it is necessary to evaluate instruments performances but also experimental procedures involved. The qualification of apparatuses requires the use of specific phantoms while the evaluation of methods requires procedures tests on non-pathological animals before experimentations. The scope of this work was to develop tools and methods to qualify imaging instruments and in vivo procedures. The need for quantification in small animal imaging, leads us to consider preclinical imaging instruments as metrological tools; which means integrating measurement uncertainty into
Joly, Candie. "Dynamique des réponses lymphocytaires T locales et systémiques à l'injection d'un vaccin dans la peau." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS317.
Повний текст джерелаVaccination has been considered as one of the greatest discoveries in the history of infectious diseases by allowing pathogens decline or eradication. However, we still ignore all the mechanism that lead to protection and therefore, fail to elaborate new vaccines against HIV, tuberculosis, malaria and emergent pathogens. Recently, efforts have been made to elicit effective cellular response after vaccination, which is crucial for pathogen clearance.This thesis relied on live-attenuated vaccine model derived from the vaccinia virus: the MVA (Modified Vaccinia Ankara) and a non-human primate model. We characterized the cellular immune response triggered by a homologous prime-boost intradermal injection of MVA, with a 2 months and 9 months boost. The MVA induced a massive infiltration of CD8 T cells at the injection site 7 days post immunization. In comparison, the systemic cellular response was mild and did not reflect the magnitude of the local response. The prime and boost injections elicited distinct orientation of the systemic and local T cells, which led to an important induction of a persistent, antigen-specific and polyfunctional CD8 and CD4 T cell responses after the 9 months boost.This work emphasizes the difference between local and systemic response, demonstrating the importance of the focus on tissue immunity. It also highlights the impact of the immunization schedule on the quality of the cellular response
Ibarrola, Danielle. "Application des techniques d'imagerie par résonance magnétique nucléaire à l'étude préclinique de l'ischémie cérébrale focale : action d'un agent de contraste superparamagnétique et essai pharmacologique de l'effet d'un antagoniste du récepteur NMDA chez le rat in vivo." Université Joseph Fourier (Grenoble), 1997. http://www.theses.fr/1997GRE19003.
Повний текст джерелаHamidou, Amine. "Analyse des interactions entre l'animal et son environnement physique et social : exemple d'un mutant neurologique : la souris Staggerer." Nancy 1, 1994. http://www.theses.fr/1994NAN10046.
Повний текст джерелаChopard-Lallier, Sophie. "Suivi fonctionnel de la greffe d'îlots de Langerhans : interêt de l'imagerie IRM et de l'immuno-monitoring cellulaire." Thesis, Besançon, 2013. http://www.theses.fr/2013BESA3001.
Повний текст джерелаLangerhans islet transplantation allows curingtype 1 diabetes by restoring an endogenous insulin secretion. Halfof patients will resume insulin withinyears. This loss of function may be explained by the lack of monitoring tools able to diagnose an ongoing graft failure. The aims of our work were toevaluate the efficiency of MRI to diagnose islet graft rejection, and to assess the feasibility of immune cellular monitoring in transplanted patients.MRI in the rat mortelMethods: Syngeneic, allogeneic and xenogeneic islets were transplanted intra-portally to diabetic rats after labeling with superparamagnetic ironoxide nanoparticles (ferucarbotran). Images were acquired on a clinical 3T MRI scanner.Results: The signal decreasing was different between the 3 types of transplantations. At day 4, the MRI signal in allogeneic group was significantlylower while glycaemia remained normal. With a cut-off value of 84% at day 4, sensitivity of 91% and specificity of 70% were obtained.Cellular immune monitoringMethods: Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients and splenocytes from donors. Immunereactivity was assessed by the release of IFNy (ELISpot), cell prolifération (flow cytometry of Ki67), and cytokine quantification (Bioplex). Theresults were correlated to the islet graft function assessed by (5-score.Results: Patients with low islet function showed higher cellular reactivity against donor cells assessed by ELISpot IFNy ((p=0,007, r=-0,50) andproliferation index (p=0,006, r=-0,51). Patients with low graft function had higher levels of IFNy, IL-5 and 1L-17
Dinis, Tony Mickael. "Prothèse nerveuse artificielle à partir de fibroïne de soie pour la réparation et la régénération de nerfs périphériques." Thesis, Compiègne, 2014. http://www.theses.fr/2014COMP2152/document.
Повний текст джерелаPeripheral nerve injury causes sensory and/or motor functions deficits. Despite technological advances over the past 25 years, a complete recovery from these injuries remains unsatisfactory today. The autograft still considered the "gold standard" in clinical practice. This is the only technique able to offer complete functional recovery. However, the occurrence of postoperative complications in autologous nerve and the limited amount of available nerves lead to develop alternatives strategy.In this context, development of nerve graft substitutes becomes by far a clinical necessity. Despite research efforts, these artificial prostheses design based on biomaterial doesn’t allow nerve regeneration as found in autograft nerve procedures. The biomaterial used must have the physical and chemical properties similar to that of the native nerve. Silk, well known for its unique mechanical properties, proposes a good alternative to develop these prostheses. Indeed, the silk protein is commonly used in the biomedical field and regenerative medicine. This protein biocompatibility may be improved through chemical modifications to promote adhesion and cell growth by the incorporation of growth factors or other molecules of interest. Therefore, this thesis proposes to develop a new type of functionalized silk biomaterial based on two growth factors : Nerve Growth Factor (NGF) and Ciliary NeuroTrophic Factor (CNTF). Given the complex architecture that consists of nerve structure, a matrix which is able to support and manage the outgrowth of tissue becomes essential. We demonstrate the power of these aligned nanofibers (produced by electrospinning) to guide and manage tissue regeneration from different organ explants culture. Aligned silk nanofibers, were biocompatible and bio-activated by adding NGF involved for nerve regeneration. This matrix has been created with a concentration gradient of NGF to guide neuritis outgrowth in only one direction. The presence of this gradient demonstrated a better axonal growth in one direction versus the uniform concentration conditions. Nerve cells consist essentially of two cell populations which are neurons and Schwann cells. To optimize the culture and growth of these two populations, in addition to NGF, we incorporated CNTF to produce bifunctionalized nanofibers. These biofunctionalised nanofibers led to a length 3 times larger on contact with neurites. The glial cells growth, alignment and migration were stimulated by CNTF. Thus, we produced bi-functionalized nerve guidance conduits for rat implantation. The physico-chemical analyzes demonstrate the biomimetic of our guide tubes. Early studies of locomotion and observing histological sections of rat sciatic nerve, following the implementation of our conduits gave very promising results.These studies demonstrate the relevance of our nervous guides’ silk-based developed as an effective alternative to nerve autograft performed in the clinic
Tétreault, Marie-Philippe. "Modifications post-traductionnelles des canaux calciques cardiaques de type L : identification des résidus asparagine qui participent à la glycosylation de la sous-unité auxiliaire CaVα2δ1". Thèse, 2015. http://hdl.handle.net/1866/13897.
Повний текст джерелаL-type CaV1.2 channels play a key role in the excitation-contraction coupling in the heart. They are formed of a pore-forming CaVα1 subunit in complex with the intracellular CaVβ and the disulfur-linked CaVα2δ accessory subunits. CaVα2δ significantly increases peak current densities of CaV1.2. The mechanism underlying this effect is still under study but requires that CaVα2δ be trafficked at the cell surface. CaVα2δ contains 16 putative N-glycosylation sites. A study was carried out to identify the role of N-glycosylation in the trafficking and protein stability of the subunit CaVα2δ. Herein we show that enzymatic removal of N-glycans produced a 50 kDa shift in the mobility of cardiac and recombinant CaVα2δ1 proteins. Simultaneous mutation of the 16 Asn sites was required to fully account for this change in protein mobility. Nonetheless, the mutation of only 6/16 sites was sufficient to 1) significantly reduce the steady-state cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging; 2) accelerate the degradation kinetics estimated from cycloheximide chase assays; and 3) prevent the CaVα2δ1-mediated increase in peak current density and voltage-dependent gating of CaV1.2. Reversing the N348Q and N812Q mutations in the non-operational 6 Asn mutant functionally rescued CaVα2δ1. Single mutation N663Q and double mutations N348Q/ N468Q, N348Q/ N812Q, N468Q/N812Q decreased protein stability/synthesis and abolished steady-state cell surface density as well as upregulation of L-type currents. These results demonstrate that Asn663, and to a lesser extent Asn348, Asn468, and Asn812 contribute to the stability of CaVα2δ1 function and furthermore that N- glycosylation of CaVα2δ1 is essential to produce functional L-type Ca2+ channels.
Segura, Emilie. "Déterminants moléculaires du clivage protéolytique nécessaire à la fonction de la sous-unité CaVα2δ1 du canal calcique CaV1.2". Thèse, 2016. http://hdl.handle.net/1866/18902.
Повний текст джерелаVoltage-gated calcium channels CaV1.2 play an essential role in the regulation of cardiac excitability. Functional channels are formed by the CaVα1 subunit and the intracellular CaVβ and the extracellular CaVα2δ1 subunits. CaVα2δ1 are type I transmembrane proteins that undergo a posttranslational modification producing their association at the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor. The molecular determinants required for the proteolytic cleavage of the recombinant CaVα2δ1 protein were studied using biochemical, immunocytochemical, fluorescence, and electrophysiological methods. Enzymatic treatment with a phospholipase C specific for the cleavage of phosphatidyl inositol lipids abolished the colocalisation of CaVα2δ1 with a plasma membrane marker as shown using live-cell confocal imaging. Single point mutations G1060I or G1061I in the predicted transmembrane CaVδ domain was shown to significantly reduce the cell surface fluorescence of CaVα2δ1 as characterized by two-color flow cytometry assays and confocal imaging, and to prevent the CaVα2δ1-mediated increase in the peak current density and voltage-dependent gating of CaV1.2 currents. The isoleucine mutations were also associated with a change in the migration pattern of the C-terminal fragments suggesting that proteolytic processing was altered. Single glycine to alanine mutations preserved the protein properties but the double mutant G1060A/G1061A significantly impaired cell surface expression of CaVα2δ1 and its functional regulation of CaV1.2. Altogether our data support a model where one Glycine residue at position 1060 or 1061 is required to produce the dominant proteolytic cleavage of CaVα2δ1 and further suggest that the GPI-anchored form of CaVα2δ1 is essential for channel function.
Fénelon, Karine. "Les mécanismes synaptiques et intrinsèques qui sous-tendent l’activité des cellules réticulospinales (RS) en réponse à une stimulation sensorielle de type cutané chez la lamproie." Thèse, 2008. http://hdl.handle.net/1866/2836.
Повний текст джерелаIn various animal species, sensory information can initiate locomotion. This relies on the integration of sensory inputs by the central nervous system. In lampreys, the spinal locomotor networks are activated and controlled by the reticulospinal cells (RS) which constitute the main descending system. In turn, RS cells receive information coming from various synaptic inputs such as the sensory afferents. Once activated by a brief cutaneous stimulation of sufficient strength, RS cells display sustained depolarizations of various durations that rely on calcium-dependant intrinsic properties and lead to the onset of escape swimming. During the course of this Ph.D, we aimed at determining whether synaptic inputs can modulate the duration of the sustained depolarizations and if the different populations of RS cells share the same integrative properties, possibly involving the internal calcium stores. First, our results show for the first time that excitatory glutamatergic inputs, including ascending spinal feedback, contribute to prolong the sustained depolarizations for long periods of time. Cutaneous inputs do not contribute to maintain the sustained depolarizations and inhibitory glycinergic and GABAergic inputs are not sufficient to stop them. Second, we show that in response to cutaneous stimulation, the RS located in the four reticular nuclei display a similar activation pattern and can all produce sustained depolarizations which do not depend on internal calcium release to be maintained. Finally, the results obtained during this Ph.D allowed us to better understand the cellular mechanisms by which the RS cells integrate and transform a brief sensory information into a sustained response associated with a motor command.