Tesis sobre el tema "Transitoire accidentel"
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Matteo, Laura. "Modélisation unidimensionnelle du comportement d’une pompe rotodynamique en fonctionnement normal et accidentel". Thesis, Paris, ENSAM, 2019. http://www.theses.fr/2019ENAM0038/document.
Texto completoConversion of mechanical energy into pressure inside a fluid -or inversely-, is necessary in numerous industries: transport, electricity production, air circulation... Rotating machineries are often used in these frames. They are constituted of at least one bladed rotating part giving energy to the fluid (the impeller) and connected to a shaft, which is entrained by a motor in the case of a pump. The design method of such turbomachines has evolved from the begining of the last century to these days. Nowadays Computational Flow Dynamics (CFD) local scale computations are used to optimize the pump components. Local simulation allows to obtain information on what is happening inside the machine in three dimensions. However, qualification of the local results of such simulations remains a challenge, mostly due to constraints on experimental technics. Additionally, computation cost of such local simulations is heavy even at the scale of the machine alone. That hardly allows the simulation of transient scenarii on whole and complex systems such as a reactor, which are studied in the frame of nuclear safety in particular. And even more when uncertainty propagation studies are intended, which involve a large number of simulations. In such a context, a model of an intermediate scale -between the global study of the machine using velocity triangles and local CFD computations- has been developed during this PhD thesis. The proposed approach consists in considering a mean stream line that is adopted by the flow inside each part of the machine, associated to a one-dimensional (1D) meshing. By defining main geometrical characteristics of the machine, it can predict its performances in terms of pressure rise and energy given to the fluid. Several turbomachines have been modelled using this 1D model: centrifugal pumps, mixed flow pumps and a radial compressor. Various working fluids have been simulated, such as water, liquid metal sodium and air non-condensable gas. Single-phase and two-phase flow regimes have been represented in those machines in steady and transient conditions. The model is able to predict performances of machines of various geometries in steady single-phase conditions with a relative error globally less than 15% for a large range of flow rates. The model allows also to detect the occurrence of cavitation for a centrifugal pump in various conditions of flow rate. It catches also pump fast startup transient dynamics in single-phase conditions. It subsists numerical difficulties when simulating the same transient in cavitating conditions. A pump modelled as described here can be included into the modelling of closed experimental loops or complex facilities such as nuclear reactors. This work opens up new possibilities to study accidental transient in the frame of safety analysis. Intented application prospects of the model are the modelling of turbines or multi-stage machines and the use of other fluids
Martin, François. "Modélisation avancée neutronique-thermohydraulique pour les MSR (Réacteurs à Sels Fondus) de type RNR à combustible liquide". Electronic Thesis or Diss., Université Grenoble Alpes, 2024. http://www.theses.fr/2024GRALI004.
Texto completoA molten salt reactor (MSR) is a GEN-IV nuclear reactor type where a liquid, high-temperature salt acts as both the fuel and the primary coolant. This characteristic has two main impacts : a strong density feedback and the delayed neutron precursors transport with the fuel salt.These two aspects require adapting the calculation codes used for nuclear reactor studies. In CEA, a coupled code was developed for MSRs studies, combining the deterministic neutronics code APOLLO3® and the CFD code TrioCFD. The objective of the PhD is to study the turbulent fluctuations in MSRs, using the coupled tool APOLLO3®-TrioCFD.In a first step, a validation step of the coupled tool was performed on the first MSR ever built, the Aircraft Reactor Experiment (ARE). Numerous experiments have been performed and documented on the ARE, which enabled comparisons between the experimental results and the simulations performed on a numerical model of the ARE.In a second step, the coupled tool was used to model the Molten Salt Fast Reactor (MSFR) concept, developed for twenty years in CNRS first, then within a European consortium. The MSFR possesses a toroidal core shape where a highly turbulent fuel salt flows. The first calculations performed on the MSFR were purely CFD (RANS and LES turbulence models), in order to resolve accurately the thermal-hydraulics model of the steady-state flow of the reactor. These first calculations also lead to early estimates of the power fluctuations in the core.Eventually the coupled neutronics – thermal-hydraulics system was studied, in order to analyse the respective impacts of each physics. Precise estimates of the temperature and power fluctuations in the MSFR core were obtained
Droin, Jean-Baptiste. "Modélisation d’un transitoire de perte de débit primaire non protégé dans un RNR-Na". Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAI044/document.
Texto completoWithin the framework of the Generation IV Sodium-cooled Fast Reactor (SFR) R&D program of CEA (French Commissariat à l’Energie Atomique et aux Energies Alternatives), safety in case of severe accidents is assessed.Such transients are usually simulated with mechanistic codes (such as SAS-SFR and SIMMER III). As a complement to these codes, which give reference accidental transient calculations, a new physico-statistical approach is currently followed by the CEA; its final objective being to derive the variability of the main results of interest for safety. This approach involves a fast-running description of extended accident sequences coupling physical models for the main phenomena to advanced statistical analysis techniques. It enables to perform a large number of simulations in a reasonable computational time and to describe all the possible bifurcations of the accident transient.In this context, this PhD work presents the physical tool (models and results assessment) dedicated to the initiation and primary phases of an Unprotected Loss Of Flow accident (i.e. until the end of sub-assemblies degradation and before large molten pools formation). The accident phenomenology during these phases is described and illustrated by numerous experimental evidences.It is underlined that the features of the new heterogeneous core concept (called CFV of the French ASTRID prototype) leads to different kinds of ULOF transients than those occurring in the previous past homogeneous cores (SuperPhenix, Phenix...). Indeed, its negative void effect drops the nuclear power when sodium heats-up and possibly boils. This enables three types of ULOF transients characterized by various core final states; the first two types leading to final coolable core states in natural circulation flow (the first one in single phase, the second one in stabilized two-phase flow) whereas the core undergoes a flow excursion followed by sub-assemblies degradation in the last type. In this study, a particular attention is paid to stabilize boiling occurrence which leads to minimize severe accident consequences.The phenomena occurring during the various ULOF transients are modelled in accordance to the level of details required to catch all the possible bifurcations of the transient. The tool coupled different (2D, 1D and 0D) models of thermics, thermo-hydraulics, core degradation (material melting and motions) and neutronics. The assumptions associated to these models are highlighted, discussed and validated. The physical tool capability of simulating the various realistic ULOF transients (without boiling, with stabilized boiling or flow excursion after boiling) is demonstrated by comparisons to experimental results (GR19, SCARABEE experiments) and to mechanistic simulations (CATHARE2 and SIMMER III).Parametric studies are then carried out on two variables: the fuel burn-up and the model of neutronic feedbacks. They underline the important influence of these parameters on the transient and the final core state. Finally, a preliminary sensitivity analysis (2000 simulations) is performed on 26 uncertain parameters (linked to initial core configuration, accident features, model uncertainties and radial nodalization). The variability of the final core state is underlined and quantified; only around 25% of cases lead to core degradation. The main influent parameters on transient phenomena are also identified, enabling to prioritize core design and safety studies.In the future, this tool will be used for safety-informed design and stability analyses of fast reactor systems, allowing to emphasize the main dominant phenomena and trends of significance for safety assessment
Lemesle, Martin Martine. "Epidémiologie des accidents vasculaires cérébraux et des accidents ischémiques transitoires dans la ville de Dijon, France". Dijon, 2000. http://www.theses.fr/2000DIJOMU10.
Texto completoCherif, Mona. "Prévalence de la valve d'Eustachi et implication dans les accidents cérébrovasculaires ischémiques". Paris 13, 2004. http://www.theses.fr/2004PA130010.
Texto completoGaffet, Berteaux Béatrice. "Intérêt de l'exploration électrophysiologique endocavitaire dans les accidents ischémiques transitoires d'étiologie indéterminée". Lille 2, 1994. http://www.theses.fr/1994LIL2M243.
Texto completoBoulanger, Marion. "Amélioration de la prévention secondaire après un infarctus cérébral ou un accident ischémique transitoire (AIT)". Thesis, Normandie, 2019. http://www.theses.fr/2019NORMC416.
Texto completoThe current long-term prognosis after transient ischaemic attack (TIA) or ischaemic stroke is not well known. I aimed to determine the long-term absolute residual risks of recurrent stroke and coronary events after TIA or ischaemic stroke and identify individuals who remain at high absolute risk of recurrent ischaemic events despite current secondary prevention management.In a population-based cohort of consecutive TIA or ischaemic stroke patients (OXVASC study, 2002-2014), the overall absolute risks of recurrent ischaemic stroke and coronary events after TIA/ischaemic stroke have decreased over the study period, and are likely to be explained by the improvement of secondary prevention over time. However, despite current secondary prevention, the subgroups of patients with prior coronary artery disease and those without prior coronary artery disease but with an Essen score of 4 remain at sufficiently high absolute risk of recurrent ischaemic events to justify more intensive treatment. Nevertheless, future secondary prevention therapies would need to achieve a substantial absolute risk reduction to outweigh increased side effects or cost compared to current therapies. Indeed, in these high-risk subgroups, more intensive lipid-lowering therapies might be justified, but we showed that the total cost of PCSK-9 inhibitors seems to exceed the generally accepted cost-effectiveness threshold while benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding
Scheiff, Valentin. "Etude expérimentale et modélisation du transfert de chaleur de l'ébullition transitoire". Thesis, Toulouse, INPT, 2018. http://www.theses.fr/2018INPT0145/document.
Texto completoThe study of rapid transient boiling is an important issue in the nuclear safety. Such a phenomenon may occur in the case of a RIA (Reactivity Initiated Accident) in the core of a nuclear reactor powerplant, where a power excursion can trigger the formation of a vapour film around the fuel rod, leading to an important rise of the rod temperature and a risk of failure. Some studies in reactor conditions provided transient boiling curves but the modeling lacks of reliability. In collaboration with the IRSN (Institut de Radioprotection et de Sûreté Nucléaire), an experiment model was built at the Institute of Fluid Mechanics of Toulouse. It generates the flow of a refrigerant, HFE7000, in a semi-annular section channel, whose inner wall is made of a metal foil rapidly heated by Joule effect, simulating the heating of a fuel rod. Infrared thermography is used to measure the temperature of the metal foil, painted with a black paint to increase its emissivity, causing also an increase of the wall thermal resistance. The measurement accuracy of the interest temperature has been optimized according to the paint thickness and a correction on the energy balance takes account this parameter. These measurements are coupled with a high-speed camera that allows visualizing the boiling regimes and get bubble sizes using image processing algorithms. On a flux-temperature diagram, the heat transfers are represented both for steady and transient regimes. Each boiling regime is then reviewed : convection, onset of nucleate boiling, nucleate boiling, boiling crisis, film boiling and rewetting. Steady regimes are correctly modeled by usual correlations. Transient convection is characterized over the whole wall and its evolution is closed to the quasi-steady solution. It is shown that heat transfer during the transition to nucleate boiling are strongly related to the formation of a large vapor phase that spreads on the wall. A local study of this propagation is then necessary. In order to simulate and control transient temperature during nucleate boiling, a P.I.D. is implemented to impose a steady or ramps temperature (from 5 to 500 K.s 1 ). The results in nucleate boiling make it possible to recover the results of the literature in both steady and transient conditions. The experiment allows to study the heat transfer when a vapor film is formed and insulates the wall. The film boiling regime during heating or the cooling of the wall can thus be stabilized for several seconds with this system. The conditions for triggering of film boiling are thus characterized, as its spread dynamic and its transfers once established. Finally, the implementation of the physical characteristics of our experience in IRSN’s SCANAIR code allows us to begin to calculate and compare our experimental results with numerical simulations. Unsteady conduction calculations are applied to the measured temperature to analyze our results during the convection regime and after the onset of boiling
Lelong, Dominique. "Etablissement d'un nouveau modèle murin d'accident vasculaire cérébral : l'amaurose transitoire chez la souris". Paris 7, 2012. http://www.theses.fr/2012PA077144.
Texto completoThis study aims to characterize a new murin model of retinal ischemia, reproducing amaurosis fugax physiopathology. Amaurosis is a therapeutic emergency but its acute treatment remains controversial. Its poor prognosis when it is not quickly reversible, the difficulty to conduct decisive randomized prospective clinical trials, and the limitations of the existing animal models, makes the establishment of a new retinal ischemia preclinical model a priority for the field. We established, for the mouse, by observation of flat-mounted retinas after fluorescein systemic injection that the ligature of the pterygopalatin artery, coupled with the section of the homolateral external carotid artery interrupts the ipsilateral retinal blood circulation. Ligature's withdrawal comes along with retina reperfusion. Four weeks after a 30 min ischemic episode, significant functional changes quantitatively measurable by electroretinography contrast with a preserved histology. A preliminary qRT-PCR study of some ischemic key genes expression had for purpose to supply temporal biomarkers useful for the later design of therapeutic protocols. This purely vascular amaurosis fugax model is simple, reversible, reproducible, usable to the rat as to the mouse. It comes to complete the already available murin stroke models and can be also adapted to modelize diverse clinical situations of retinal ischemia
CARO, JOSEPH. "Interet des plaquettes marquees a l'indium 111 dans le bilan des accidents vasculaires cerebraux transitoires". Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20069.
Texto completoBennis, Youssef. "L'Erythropoïétine, agent d'optimisation de la thérapie cellulaire par progéniteurs endothéliaux dans l'AVCischémique et l'ischémie aiguë des membres inférieurs". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5500.
Texto completoHanna, Georges. "Les accidents ischémiques cérébraux de l'adulte jeune : enquete étiologique menée au C.H.R. de Bordeaux entre janvier 1990 et avril 1993 : à propos de 55 cas". Bordeaux 2, 1993. http://www.theses.fr/1993BOR23053.
Texto completoWASZKIEWICZ, JEAN-MARC. "Valeur predictive de la debimetrie sanguine cerebrale dans les accidents ischemiques transitoires : a partir de 42 observations". Lille 2, 1990. http://www.theses.fr/1990LIL2M132.
Texto completoClamens, Olivier. "Analyse et propagation des incertitudes associées à la dépressurisation de l’Hélium 3 sur les transitoires de puissance du réacteur CABRI". Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAI061/document.
Texto completoCABRI is a pool type pulsed reactor designed for studying pre-irradiated nuclear fuel behavior under RIA (Reactivity Initiated Accident) conditions.The helium-3 depressurization from the transient rods system allows the insertion of up to 4 $ reactivity mainly countered by the Doppler effect when the power reaches in few milliseconds up to 200,000 times the initial 100~kW power.This thesis presents the improvements added to the power transients prediction and the associated uncertainties studies.The point kinetics calculation coupled with 1D thermal-hydraulics and heat transfer has been improved by the addition of surrogate models based on experimental analysis and Best-Estimate calculations of the helium-3 depressurization and of the reactivity effects and of the kinetics parameters.The power transients modeling improvements have a positiv impact on the CABRI tests prediction.The propagation of the experimental and of the modeling uncertainties was realized with the SPARTE code and the URANIE uncertainty platform.Finally, the power transients characteristics optimization is approached in order to improve the CABRI experiments designing
Quenault, Aurélien. "Apport de l'imagerie par résonance magnétique dans l'accident ischémique transitoire : imagerie moléculaire de l'inflammation et imagerie du système glymphatique". Caen, 2015. http://www.theses.fr/2015CAEN3150.
Texto completoTransient ischemic attack (TIA) is a transient episode of neurological dysfunction caused by focal ischemia without acute infarction on brain imaging. TIA is major sign of ischemic stroke. Therefore TIA requires rapid assessment to evaluate and manage this risk. However, TIA diagnosis is difficult due to many differential diagnoses. This results in a waste of opportunity for some patients and unnecessary consumption of expensive resources for other. Therefore it is necessary to identify new tools and new approaches to understand the pathophysiology of AIT and for better evaluation. We have developed a preclinical model of TIA in which, thanks to two non-invasive and semi-quantitative techniques of magnetic resonance imaging (MRI) we have: I) shown a deficit of the glymphatic system, a key regulator of the exchanges of metabolites in the extracellular spaces of the brain parenchyma; ii) developed molecular imaging of P-selectin, which can reveal cerebrovascular inflammation after TIA. Imaging of the glymphatic system unmasks tissue abnormalities and may improve the risk assessment after TIA. Molecular imaging of P-selectin could identify vascular territories at risk and areas impacted by the ischemia. The clinical application of these results could improve diagnosis and management in the context of TIA
BOILLET, GERARD NADINE. "Les accidents ischemiques transitoires dans le territoire carotidien chez les sujets de moins de 65 ans : etude epidemiologique sur 46 dossiers ; bilan etiologique, prevention secondaire, surveillance". Reims, 1989. http://www.theses.fr/1989REIMM108.
Texto completoRoques, Sébastien. "Modélisation du comportement dynamique couplé rotor-stator d'une turbine en situation accidentelle". Phd thesis, Ecole centrale de nantes - ECN, 2007. http://tel.archives-ouvertes.fr/tel-00353938.
Texto completoKuntz, Mélanie. "Influence de l'environnement périvasculaire cérébral sur la dysfonction de la barrière hémato-encéphalique au cours d'une ischémie transitoire". Thesis, Artois, 2013. http://www.theses.fr/2013ARTO0409/document.
Texto completoIn the recent years, while no neuroprotective agent was clinically effective in reducing brain ischemic damage, the neurovascular unit (NVU) concept emerged as a new paradigm for stroke investigation and treatment. The breakdown of the blood-brain barrier (BBB), localized in brain capillaries, with ensuing vasogenic edema and intracerebral hemorrhage, appears as a critical event of this disease, and severely restricts the eligibility of patients for rtPA thrombolysis, the only acute-phase treatment currently available. The complex intercommunications occurring within the NVU makes the microvascular dysfunction difficult to study in vivo, highlighting the importance of in vitro approaches to complete the knowledge in this field. In this context, the work done in this PhD demonstrates that brain tissue necrosis influences the kinetics of the loss of BBB integrity during reperfusion. However, even when the BBB remains functional in a non-lesional ischemic context, it becomes vulnerable to certain molecules such as rtPA in a thrombolysis situation. These results illustrate the key role of molecular perivascular environment on the BBB dysfunction during cerebral ischemia, and orientate new therapeutic strategies towards the protection of the entire NVU
Nop, Raksmy. "Experimental investigation and modeling of the transient flow boiling crisis of water at moderate pressure and high subcooling". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPAST046.
Texto completoIn case of a reactivity insertion accident in an experimental nuclear reactor, heat generation in the core can grow exponentially in time, with a power escalation period ranging from a few to a few hundreds of milliseconds. Due to neutronic and thermohydraulic effects, boiling crisis may arise, possibly leading to an explosive reaction. If the boiling Crisis has been widely investigated in steady-state conditions, this has not been the case for transient heat inputs. The aim of the present work is to understand and to predict the transient flow boiling crisis in the conditions of moderate pressure and high subcooling. To this end, an experimental campaign has been realized making use of space and time highly resolved videos and IR thermography covering a wide range of experimental parameters. The analysis of the massive amount of data produced by these experiments gives a better insight on the dependency of the transient Critical Heat Flux to the different parameters of interest (power escalation period, flow velocity, subcooling, pressure, channel width, heating length). Moreover, their fine analysis enables to highlight the underlying mechanisms. For conditions of forced flow and high subcooling, the bubbles generated at the wall present a pulsating behavior. This specific process leads to an efficient heat transfer from the wall to the neighboring fluid. Boiling crisis is stated to occur when a thin layer of liquid contacting the wall reaches the saturation temperature. Starting from these observations, a model is developed which brings to light two non-dimensional parameters useful to describe the transient nature of the process and the dominant cooling processes. With the knowledge of the steady-state CHF, the model permits to conservatively estimate the value of the Critical Heat Flux for any power escalation period and subcooling. This model is now ready for implementation into simulation codes to investigate nuclear accidental transients
Shin, Hyeong-Ki. "Analyse de transitoires pouvant conduire les coeurs de réacteurs à eau dans des situations dégradées, analyse des configurations résultantes". Aix-Marseille 1, 1999. http://www.theses.fr/1999AIX11024.
Texto completoSakael, Clément. "Modélisation de la microstructure des alliages de Zirconium irradiés : application à un transitoire Accident de Perte de Réfrigérant Primaire et à la restauration en aval du cycle". Electronic Thesis or Diss., Centrale Lille Institut, 2023. http://www.theses.fr/2023CLIL0010.
Texto completoThe subject of this thesis concerns zirconium alloys which are used to manufacture the fuel rod cladding and fuel assemblies of pressurized water nuclear reactors. This type of alloy is chosen in the nuclear field for its low thermal neutron capture cross section. However, under neutron irradiation, changes in shape and volume, an increase in hardness and a significant reduction in the ductility of the material are observed, which means an increase in its embrittlement. This work focuses on the irradiation-induced growth of the cladding that results from an elongation in the basal plane and a contraction along the c ⃗ axis of the hexagonal lattice of the alpha phase of zirconium. This phenomenon amplifies beyond a threshold dose that coincides with the nucleation of dislocation loops and the formation of loop alignments as layers parallel to the basal plane. Nevertheless, the mechanisms of nucleation of defect clusters such as dislocation loops are still to be clarified. In order to have a better understanding of these phenomena, a multi-scale approach was used to model the evolution of the microstructure of zirconium alloys (i) during irradiation, (ii) during the transient phase of a loss-of-coolant accident (LOCA) and (iii) during the downstream restoration of the cycle. First, atomic scale calculations based on density functional theory (DFT) and empirical potentials are performed to determine the properties and characteristics of point defect clusters (self-interstitial clusters, vacancy clusters and dislocation loops).In order to have a better characterization of self-interstitial, the migrationenergies and diffusion coefficients of di- and tri-self-interstitials are calculated in moleculardynamics using DFT. Some of the results obtained by atomistic calculations are used as inputdata for an object kinetic Monte Carlo (OKMC) code, which simulates the evolution of themicrostructure of zirconium under conditions (i) to (iii)
Zouari, Ahmed. "Comportement des gaines en alliages de zirconium en conditions thermo-mécaniques représentatives d’un accident RIA". Thesis, Université Paris sciences et lettres, 2020. http://www.theses.fr/2020UPSLM058.
Texto completoThe aim of this work is to enhance the understanding of the thermomechanical behavior at rupture of the fuel rod cladding during an accidental transient of the RIA type. A new mechanical test has been developed in order to apply a strain biaxiality ratio ɛzz/ɛ00 between -0,2 et 1. It allows reproducing loading conditions close to the ones occurring during a RIA accident. An experimental campaign at room temperature carried out with this device made it possible to study the effects of strain biaxiality ratios and strain rate on the fracture of the cladding. The tests carried out show a significant effect of the biaxiality on the hoop strain at failure which has a minimum of a plane strain state where the strain biaxiality is close to 0. A slight decrease in ductility was also recorded during the increase in the strain rate for all biaxiality levels. The damage mechanisms and failure modes of specimens are identified from the surfaces and failure profiles depending on the stress conditions. Numerical finite element simulations were performed with the CAST3M code to model the test and simulate the failure of cladding with biaxial loading. A second experimental device has been developed to couple the effects of biaxial mechanical loading and rapid thermal loading. The objective is to heat the cladding with temperature rise rates greater than 100 °C.s-1 in order to avoid the restoration of the defects linked to the hydriding and to the irradiation during the test. The method was used to perform thermomechanical tests at high heating rates, high strain rates, and high biaxiality levels to reproduce full loadings in a reactivity accident. The first results show, for a virgin cladding, that the strain at the break was not affected by temperature or by the rate of heating. Finite element simulations were undertaken to model the different heating methods tested and to optimise the chosen method. These simulations made it possible in particular to model the passage of electric current and heat flow through solid-solid interfaces
Jean-Leblanc, Noémie. "La voie canonique Wnt est nécessaire pour le maintien de l'intégrité de la barrière hémato-encéphalique après un accident vasculaire cérébral : impacts sur la thérapie thrombolytique". Master's thesis, Université Laval, 2019. http://hdl.handle.net/20.500.11794/33473.
Texto completoStroke triggers blood-brain barrier (BBB) disruption and hampers tissue recovery by impairing the local brain microenvironment. Administration of recombinant tissue plasminogen activator (rtPA) within a therapeutic window of 4.5 hours after onset constitutes the only existing treatment. Beyond this window, tPA worsens BBB disruption and causes haemorrhagic transformation. Canonical Wnt pathway induces BBB formation during ontogeny. We hypothesize here that pathway activity is required to maintain BBB integrity after stroke and that its activation might constitute a promising approach to improve rtPA therapy via protection of the BBB. Therefore, we have first assessed pathway activity in the brain of mice subjected to transient middle cerebral artery occlusion (MCAo). Next, we have evaluated the effect of pathway deactivation early after stroke on BBB integrity Finally, we have assessed the potential of pathway activation on BBB breakdown associated to the delayed administration of rtPA. Our results show that pathway activity is induced specifically in brain endothelial cells early after ischemic stroke. Early deactivation of the pathway using a potent inhibitor, XAV939, aggravates BBB breakdown, and increases the incidence of spontaneous haemorrhagic transformation, without affecting brain infarct. On the other hand, pathway activation using a potent specific activator, 6-Bromoindirubin-3’-oxime (6-BIO), attenuates BBB breakdown, and reduces the incidence of haemorrhagic transformation associated to delayed rtPA administration by inducing expression of the tight junction claudin-3, and attenuates endothelial basal permeability by repressing the expression of PLVAP, without affecting brain infarct, vascularization and inflammation. Our study demonstrates that activation of the canonical Wnt pathway constitutes a clinically relevant strategy to extend the therapeutic window of rtPA by attenuating BBB breakdown via regulation of BBB-specific mechanisms
Dupont, Damien. "Cartographie in vivo des remaniements anatomo-fonctionnels de l’architecture des réseaux neuronaux dans le système nerveux central au cours du développement par Imagerie du Tenseur de Diffusion et Imagerie renforcée par le manganèse". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA112021/document.
Texto completoThe thesis aim is to develop MRI methods to study the impact of focal transient ischemia in neonatal rat brain. The principal techniques used are MEMRI (Manganese Enhanced MRI), DTI (Diffusion Tensor Imaging) and QBI (Q-Ball Imaging). MEMRI was used to observe in a dynamic way the cortico-thalamic manganese transport combined with the structural informations extracted from the DTI experiments. Results have shown a cortico-thalamic pathway disturbance, at seven and fourteen days after ischemia. Globally DTI results have shown a slowed brain structuration. From these results, the feasibility of a fast acquisition method and the post processing steps of Q-ball protocol was established and applied in an immature rat. The different MRI protocols developed during this thesis have shown good efficiency to follow the rat brain maturation, in healthy and pathological conditions, thus opening new perspectives for brain development studies
Ducroquet, Aude. "Impact de la consommation chronique d’éthanol sur l’ischémie cérébrale : aspect clinique et aspect expérimental chez le rat". Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S069/document.
Texto completoIschaemic stroke is a major cause of disability and death in Europe. Ethanol is a widely consumed drug and chronic ethanol consumption is a participating factor in ischaemic stroke (Reynolds et al., 2003). Chronic and excessive ethanol consumption is associated with an increased risk of mortality and morbidity from ischaemic stroke (Zhang et al., 2014). It may increase consequences of ischaemic brain injury in animals (Zhao et al., 2010, Lemarchand et al., 2015). Oxidative stress and glutamatergic excitotoxicity may play an important role in exacerbating ischaemic damage following chronic consumption of ethanol (Zhao et al., 2010; Zhao et al., 2011). The primary aim of my thesis was to assess whether chronic excessive ethanol consumption has a deleterious effect on ischaemic brain damage both in human and in a rat model. The secondary aim was to study the post-ischaemic inflammation in the brain and in the liver at short and intermediate terms. Wistar male rats were subjected to chronic administration of ethanol (10% or 35% v/v, 5ml/kg, twice per day, 4 weeks prior operation) or water (vehicle), followed by middle cerebral artery occlusion (OACM). The effects of ethanol ingestion on infarct volume, neurologic and motor deficits were determined at 24 hours (J1) and at 7 days (J7) of reperfusion. We quantified the number of activated microglia in the ipsilateral hemisphere and additionally measured the number of neutrophils and levels of ICAM-1 and VCAM-1 mRNA in the ipsilateral hemisphere and liver. Further, we examined the steatosis by comparing oil-red coloration of J1, J7 and non-ischemic rats to assess the physiologic liver status in the 3 groups. Patients with supratentorial cerebral ischaemia were recruited within 48 hours of symptom onset. Heavy drinkers were defined by a weekly consumption of ≥300 g ethanol and severe ischaemic strokes (score≥6 according to the National Institutes of Health Stroke Scale, NIHSS). The NIHSS score was evaluated within 48 hours. We performed measurements of carbohydrate-deficient transferrin (CDT, biomarker of chronic excessive ethanol consumption) and inflammatory markers plasmatic levels. Being a heavy drinker and having a higher plasma level of neutrophils were independently associated with a higher baseline severity of the neurological deficit in patients with supratentorial ischemic stroke or transient ischemic attack within 48 hours. Excessive and chronic ethanol consumption in non-ischaemic rats conferred an increased hepatic steatosis and an inflammatory condition in the cortex, the striatum and the liver, observed as increased expression of adhesion proteins. However, neutrophil infiltration was not observed in the liver or in the brain. In the OACM model, chronic consumption of 35% ethanol worsened ischemic stroke lesions and motor deficits, compared to non-ethanol-exposed rats. Neutrophil infiltration and the mRNA levels of VCAM-1 and ICAM-1 are increased in the brain and in the liver of ischaemic rats exposed to 35% ethanol, compared to control ischaemic rats, at J1 and J7. The aggravation of neurologic and functional deficits was associated with increased post-ischaemic inflammation in both the liver and brain, as observed by microglial activation, neutrophil infiltration and leukocyte adhesion at short and intermediate terms