Dissertations / Theses on the topic 'Thérapie du cerveau'
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Marsac, Laurent. "Focalisation utrasonore adaptative et application à la thérapie du cerveau." Paris 7, 2013. http://www.theses.fr/2013PA077106.
The aim of this thesis is to optimize transcranial ultrasound focusing for brain therapy at 1 MHz. Tissues are heated in a non invasive way by focused ultrasound using a spherical probe. Distortion of the wavefront induced by the skull is compensated. Treatments are MR-guided in order to measure the temperature rise at focus. In vitro ultrasound measurements allowed to measure the phase and amplitude aberration on different skulls. Aberration correction based on CT scan imagine of the skull and numerical simulations are optimised and compared. The best method is applied to ex vivo human heads for validation of the accuracy. Skull aberrations are corrected by an adaptative focusing method based on the estimation of the acoustic intensity at focus. Measurement is done thanks to the displacement of the tissue induced by the acoustic radiation pressure. Measurement done by an MR-ARFI IRM sequence and validated in phantoms and cadaver heads and confirms a better focusing. The blood brain barrier (BBB) was opened on 2 animals. This is done by focusing after injection of microbubbles in blood. Local BBB opening and its closing after 24h are verified. These first applications at 1 MHz allow to prepare future applications on patients
Aubry, Jean-François. "Focalisation ultrasonore adaptative : application à l'imagerie et à la thérapie du cerveau." Paris 7, 2002. http://www.theses.fr/2002PA077012.
Chodan, Desmaris Nathalie. "Thérapie génique des atteintes neurologiques dans les mucopolysaccharidoses." Paris 7, 2004. http://www.theses.fr/2004PA077039.
Tanter, Mickael. "Application du retournement temporel à l'hyperthermie ultrasonore du cerveau." Paris 7, 1999. https://pastel.archives-ouvertes.fr/pastel-00650031.
Martina, Marie Sophie. "Conception de magnétoliposomes furtifs pour le diagnostic et la thérapie anti-cancéreuse." Paris 11, 2006. http://www.theses.fr/2006PA114831.
A novel hybrid nanosystem, resulting from the encapsulation of iron oxid nanoparticles into stercally stabilised phospholipidic vesicles, has been realised and characterised. These socalled magnetoliposomes, revealed as excellent MRI contrast agents, could be guided towards a tumor tissue or a cerebral hemisphere thanks to an external magnetic gradient
Guttin, Audrey. "Développement d’une bithérapie antitumorale basée sur une approche théranostique : applications aux cancers du cerveau et de la vessie." Thesis, Paris, EPHE, 2016. http://www.theses.fr/2016EPHE3018/document.
Solid malignant tumors have molecular characteristics that clearly distinguish them from healthy tissue. The project is to develop a new therapeutic strategy based on these molecular characteristics. We set up a new therapeutic approach so as to customize treatment by connecting it directly to the diagnosis of the tumor (theranostic approach).Brain tumours and bladder tumours are two examples of particularly aggressive solid tumours. These two types of tumors are classified into several subgroups that have their own molecular profiles. The microRNAs (miR) are molecules naturally synthesized by cells. These molecules may have a role of oncogene or tumour suppressors whose expression is strongly deregulated in tumours. So the assessment of the expression levels of few microRNA allows the distinction of gliomas of high grade compared to low grade.To set up the new therapy we needed to modulate the expression of microRNAs deregulated in tumors. The proposed approach was to counter the expression of oncogenic microRNAs overexpressed using an antimicroARN (antimiR). This type of molecule is chemically similar to the naturally occurring RNA molecules in the cells. For a better efficiency of this new therapeutic strategy, we tried to optimize the transport of the antimiR to increase the therapeutic effect. To vectorize the therapeitic antimiR to the heart of the tumor, we envisioned to chemically combine the antimiR to a cell-penetrating antitumoral compound. Chalcones derivatives which are hydrophobic have this capability. A combination of the two molecules (antimicroARN and chalcone) was evaluated and the results appeared promising
Giguère-Rancourt, Ariane. "Augmentation de la captation cérébrale du glucose par thérapie génique comme alternative thérapeutique dans la maladie d'Alzheimer : essais préliminaires." Master's thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/26443.
Impaired brain glucose metabolism is known to be one of the best predictors of cognitive decline in patients with Alzheimer’s disease (AD). A decrease in glucose transporter 1 (GLUT1) in the brain capillary endothelial cells (BCECs) of the blood-brain barrier (BBB) is observed in AD patients and animal models and might contribute to impaired brain glucose uptake in the disease. The main objective of the present work was to upregulate GLUT1 in the BCECs with a targeted delivery approach using plasmids encoding for GLUT1. Six plasmids were assembled and transfected in two cell lines. GLUT1 activity was assessed with a fluorescent glucose analog. Two plasmids were then encapsulated within an immunoliposome formulation and injected to Balb/c mice. We have generated well-characterized GLUT1-expressing plasmids for future work to confirm GLUT1 as a potential therapeutic target for AD.
Paris-Robidas, Sarah. "Caractérisation de vecteurs ciblant le récepteur de la transferrine : ciblage des cellules endothéliales du cerveau." Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/30323.
The increase in life expectancy leads to a direct expansion of the aging population. This expansion further increases the burden of neurodegenerative diseases. The development of new drugs to treat brain pathologies is greatly hindered by the presence of a physiological barrier, the blood-brain barrier (BBB), protecting the brain homoeostasis. However, a high number of specific transporters are located on endothelial cells forming the BBB and could be the target of brain-drug delivery allowing significant cerebral accumulation of many therapeutic compounds. To study the potential of monoclonal antibodies (mAb) targeting the transferrin receptor (TfR) in the context of a non-invasive gene therapy strategy, we foremost studied the cerebral distribution of the mAb Ri7. We first observed retention in the brain of the mAb. However, fluorescence microscopy analysis revealed that the distribution of Ri7 was confined to cerebral vasculature. Thereafter, by conjugating Ri7 to quantum dots (Qdot), we performed experiments to characterize the subcellular distribution of the mAb. Our transmission electron microscopy analyses showed that Ri7-Qdots were massively internalized within brain capillary endothelial cells (BCECs) and that the TfR-targeted Qdots were in small vesicles, tubular structures and multivesicular bodies. We thus identified BCECs as a potential target for the treatment of endothelial pathology of neurodegenerative diseases. Finally, we investigated the potential of two nanoformulations to delivery nucleic acids to BCECs. Our data demonstrated the capacity of polyionic complex micelles and immunliposomes to deliver a large number of nucleic acids to BCECs. Overall, our study opens the door for a novel therapeutic approach based on brain endothelial cells drug delivery.
Posvandzic, Alma. "Développement d'un vecteur lentiviral spécifique aux macrophages cérébraux activés pour la thérapie génique appliquée à des maladies du système nerveux." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/25000/25000.pdf.
Magdeleine, Christophe. "La Toxoplasmose cérébrale au cours du SIDA à la Martinique : étude de dossiers de 1985 à 1992." Paris 11, 1994. http://www.theses.fr/1994PA115049.
Gateau, Jérôme. "Imagerie ultrasonore ultrarapide d'évènements de cavitation : application en thérapie par ultrasons et imagerie de détection." Phd thesis, Université Paris-Diderot - Paris VII, 2011. http://pastel.archives-ouvertes.fr/pastel-00863591.
Droguerre, Marine. "Thérapie cellulaire de la maladie de Parkinson : transplantation intranigrale vs intrastriatale." Thesis, Poitiers, 2015. http://www.theses.fr/2015POIT2320/document.
Parkinson’s disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN), leading to a loss of dopamine in the striatum. One of the experimental therapeutic approaches in PD is the graft of DA neurons not in their ontogenic site, the SN, but directly into the target region, the striatum and those leads to variable results. In this study, we have analyzed in detail the functional outcome of fetal VM tissue expressing GFP under the control of a tyrosine hydroxylase promoter grafts placed either into the SN or striatum in unilaterally 6-hydroxydopamine lesioned adult mice. Anatomical and functional outcome were analyzed using behavioral, electrophysiological and immunohistochemical approaches. Our results show that transplanted neurons in both locations can survive and re-innervate the striatum. Furthermore, both grafts locations significantly restored motor performance and induced the recovery of striatal firing properties. However, only intranigral transplantation allows recovery of fine motor skills of previous members and efficiently normalized cortico-striatal responses
Martel, Kathya. "L'activation comportementale pour l'amélioration des symptômes dépressifs liés à un traumatisme crâniocérébral : une étude de cas." Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/69058.
Currently in Canada, more than one million people are living with the sequelae of an acquired brain injury. The incidence of brain injury outnumber breast cancer, AIDs, spinal cord injury and multiple sclerosis - combined. Traumatic brain injury (TBI) is now considered a chronic medical condition and a major public health concern whose consequences can persist and progress. Although depression is one of the psychological disorders with the highest prevalence rates post-TBI, there are few studies of nonpharmacological interventions for this issue. This lack of empirical evidence has a direct impact on TBI patients, leaving them without recognized efficacious treatment adapted to the specificities of their condition. Behavioural Activation (BA) has been demonstrated to be as effective as cognitive behaviour therapy (CBT) but is less cognitively demanding and thus potentially more suitable for people with brain impairment. However, no study has been yet done to verify its feasibility and efficacy in the TBI population. The objective of this single-case study was to preliminary evaluate the feasibility and efficacy of BA administered in a low-intensity guided self-help format for depressive symptoms in adults (18 years and older) having sustained TBI, using a single-case experimental design. This study also aimed to evaluate the potential benefits of BA regarding quality of life and social participation. Five participants with clinically significant depressive symptoms were enrolled in the study and were asked to complete mood assessments during the baseline, treatment and follow-up. Only two of them completed the entire protocol. This project demonstrated the feasibility of BA intervention on mild to moderate depression symptoms in adults with mild TBI. Modest evidence in support of BA to decrease depressive symptoms and quality of life was found but BA had no effect on social participation.
Angla, Célestine. "Fast transcranial acoustic simulations for personalized dosimetry in ultrasound brain therapy." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPAST207.
Ultrasound brain therapy is a promising method, as it is non-invasive when ultrasonic waves are sent through the skull. However, the skull bone complex structure strongly attenuates and aberrates the ultrasound beam, altering the dimensions, position and intensity of the focal spot. These focal parameters must be perfectly controlled to ensure both treatment efficacy and safety. Due to the high inter/intra-individual variability of skull geometry and acoustic properties, personalized simulations are required to predict focal characteristics depending on the patient skull and the ultrasonic probe position. Most simulation methods currently in use, such as k-Wave, are very time- and memory-intensive, limiting them to pre-intervention planning tools. The aim of this thesis was to develop a fast and realistic semi-analytical method for ultrasound field computation through the skull. As a first step, we developed a smooth and homogeneous model of the skull, realistic and suited to fast field computation algorithms. To this end, we modeled the skull inner and outer surfaces using a method called "Multi-level Bspline Approximation", and we developed a skull acoustic property homogenization method, which was numerically validated. This smooth and homogeneous skull model was then used as input to the field computation algorithm developed. This algorithm, named SplineBeam, is based on an ultrasonic path computation method that minimizes the time-of-flight function, which is fast and accurate, and which, combined with the pencil method, enables a regular sampling of the ultrasound probe. SplineBeam was validated numerically, by comparison with the pencil method, embedded in the CIVA HealthCare simulation platform, developed at the CEA, and with other numerical solvers (including k-Wave) on a series of configurations, and experimentally, by comparison with hydrophone measured pressure fields through an ex vivo skull sample. SplineBeam simulated fields were found to be closer to the experimentally measured ones than those simulated with k-Wave. This validates both the skull model and the field computation method. Furthermore, SplineBeam can restrict its computation to the focal spot, which allows it to drastically reduce the number of computation points, making it faster than k-Wave by two orders of magnitude, for a large probe
Vasques, Xavier. "La stimulation cérébrale profonde dans le traitement des syndromes dystono-dyskinétiques : modélisation tridimensionnelle de la distribution des paramètres électriques appliquée au globus pallidus interne." Montpellier 1, 2008. http://www.theses.fr/2008MON1T017.
Simon, Thomas. "Traitement anti-angiogénique par le bevacizumab des tumeurs gliales malignes : étude in vitro dans une matrice tridimensionnelle." Rouen, 2014. http://www.theses.fr/2014ROUES032.
Glioblastomas (grade IV gliomas) are one of the most invasive and aggressive solid tumors. Bevacizumab, a humanized monoclonal antibody directed against the pro-angiogenic factor Vascular and Endothelial Growth Factor-A (VEGF-A), is used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating intracellular survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in Hyaluronic Acid (HA) hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Identification of mediators involved in the direct effect of bevacizumab on glioblastoma cells and the resulting downstream signaling pathways will help to develop multi-targeted therapies useful in the treatment of glioblastomas
Tabouret, Emeline. "Glioblastome et angiogenèse : profils évolutifs, interaction avec l'invasivité et implications thérapeutiques." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5012/document.
Glioblastomas 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
Fayek, Racha. "Progéria de Hutchinson-Gilford : identification de biomarqueurs et exploration préclinique de nouvelles approches thérapeutiques." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5017.
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease characterized by premature, accelerated and segmental aging with an estimated incidence of 1 in 4 to 8 million of births. Children with HGPS present with major growth retardation, lipodystrophy, distal osteolysis and cardiovascular defects that cause their death at the mean age of 13 years. In 2003, our team discovered the causative mutation of HGPS in the LMNA gene. Despite being predicted as silent (c.1824 C>T; p.Gly608Gly), this de novo mutation activates a cryptic splicing site leading to the production of a truncated, aberrantly prenylated and toxic form of lamin A, called progerin. The main objectives of this thesis have been: 1) characterizing molecular and cellular biomarkers in HGPS or related syndromes patients' cell lines, together with the progeria mouse model LmnaG609G/G609G, 2) characterizing cognitive aspects as well as lamins' and progerin expression in the central nervous system in the same in vivo model and 3) the developement, in vitro and in vivo, of novel therapeutic approaches for progeria using either resveratrol, an antioxidant molecule, or micelle-coated antisense oligonucleotides with the intent of adapting an oral treatement for progeria children
Mondou, Paul. "Contrôle intelligent de la cavitation des microbulles à travers le crâne pour l'optimisation des thérapies ultrasonores." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPAST188.
The blood-brain barrier (BBB) is the primary interface for exchanges between blood and brain tissue. It remains a major obstacle in the therapeutic management of neurological or cancerous pathologies of the central nervous system (CNS), as over 95% of drugs struggle to reach targeted brain tissues due to the BBB. Approaches optimizing the cerebral delivery of active compounds are crucial to enrich the therapeutic arsenal against CNS pathologies. Since 2001, the use of ultrasound, combined with microbubble injection, has provided a non-invasive method for transient, local, and repeated opening of the BBB without tissue damage. This technique requires rigorous control of in-situ ultrasonic dosimetry: microbubbles need sufficient intensity for effective action (stable cavitation) without oscillating too strongly (inertial cavitation) to avoid the risk of implosion and local adverse effects. Dosimetry is challenging due to the presence of the cranial bone, which is highly heterogeneous and varies among individuals. It has been demonstrated that measuring the oscillation state of microbubbles (cavitation) is possible with the ultrasonic signals backscattered by them. Thus, stable microbubbles reflect only harmonics of the emission frequency, while imploding microbubbles reflect a broaddeband signal characterized by emission at all frequencies. Algorithms have been developed to adjust the ultrasound emission pressure in real-time based on the signals backscattered by microbubbles. This thesis focuses on cavitation control through algorithms using different indices calculated from cavitation signal spectra. The work benefited from ultra-fast electronics, Field Programmable Gate Array, (FPGA) that drastically accelerated the implemented control. An experimental setup was initially constructed to place a stream of microbubbles at the focus of a therapeutic ultrasound transducer. This in vitro device recorded ultrasonic signals backscattered by oscillating microbubbles under various acoustic pressures. The measurements optimized the calculation of indices characterizing different cavitation states. Following these tank measurements, cavitation measurements were conducted during BBB permeabilization experiments in vivo. These results were compared to in vitro results to correlate different cavitation states with biological observations: presence or absence of BBB permeabilization or vascular damage. Based on these results, a cavitation regulation algorithm exploiting the speed provided by the FPGA was constructed. It operates by progressively increasing the acoustic pressure during each ultrasound pulse while maintaining the pressure just below the inertial cavitation threshold. This algorithm was tested in vitro and in vivo. Finally, in a translational approach towards clinical application, cavitation measurements were performed ex vivo using a human half-skull. These measurements demonstrate our ability to capture the necessary indices for the proper functioning of cavitation control algorithms in humans under conditions where the signal is degraded by the substantial thickness of bone to penetrate
Lapre, Emiline. "Maladie d’Alzheimer et thérapies non médicamenteuses : évaluation de la stimulation cognitive et de l’activité physique sur le fonctionnement exécutif." Thesis, Bordeaux 2, 2010. http://www.theses.fr/2010BOR21764/document.
The principal objective of this thesis was to evaluate the therapeutic impact of an intervention which combines a cognitive stimulation program and a physical activity program in mild to moderate Alzheimer's disease. Specifically, the objective was to detail the respective and combined effects of these interventions in the three following dimensions, 1) general cognitive functioning, 2) executive functioning with updating, switching, inhibition and planning, 3) psychosocial functioning, including anxiety and depression. The main study of this thesis examines the pre-and post-intervention scores of 67 patients assigned into four groups (i.e., cognitive stimulation, physical activity, cognitive stimulation combined with physical activity, and control). The data showed that, 1) cognitive stimulation improved general cognitive functioning and maintained updating and switching abilities, 2) physical activity improved inhibition and switching abilities, and 3) associate cognitive stimulation and physical activity allowed the improvement of general cognitive functioning, inhibition and switching abilities, and allowed remaining updating abilities. Taken together, these results demonstrate the therapeutic effects of cognitive stimulation and physical activity in Alzheimer's disease treatment. Moreover, the data collected showed that the benefits of the interventions were particularly important when the program included both interventions. Mechanisms of changes in cognition of Alzheimer's patients are discussed through the concept of cognitive reserve. The aim for future researches is to develop programs of cognitive stimulation and physical activities to preserve executive functioning
Demeulemeester, Morgane. "Développement de stratégies d’intervention innovantes face au symptôme hallucinatoire précoce : apport de la cognition et des nouvelles technologies." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S058/document.
In its contemporary conception, the hallucination is simply defined as a ‘perception without object to perceive’. It remains however complex to highlight it in clinical practice, in particular in pediatric population. The clinical interview, during which the clinician have to avoid stumbling blocks, such as psychic immaturity and potential existence of an imaginary companion, can be completed by methods allowing a more specific caracterisation of the phenomenon. This symptom has been a renewed interest in the last 30 years in scientific domain. It is now accepted that the hallucinations are not found exclusively in schizophrenic etiological context, but they can also occur during normal development and be spontaneous resolution. Despite this, few studies currently have a specific interest in its early and transdiagnostic character, and his treatment in children and adolescents.Nevertheless, differents strategies for actions are available to help us better understand this symptom, whether its evaluation or therapeutic. In this PhD work, we initially focused on cognitive aspects of hallucination. Based on the source monitoring framework, assuming that hallucinations are the result of a tendency to attribute more often self-generated events to an external subject, we standardized a task assessing this cognitive ability.We first highlight an age effect in our healthy subjects enrolled in the study of standardization, preferentially for the reality monitoring task (distinction between an external source and an internal source). We then compare these data with those obtained from patients suffering from schizophrenia, revealing loss performance for both tasks. Our goal is then to obtain normative data for a pediatric population.In a second step, we are interested in the psychometric assessment of early-onset hallucinations. Given the lack of tools, we have combined the playfulness of new technologies in a comprehensive and rigorous assessment of the symptom. We thus developed an application for touchpad associating the assessment of cognition, including the theory of mind, and symptom severity. Theory of mind developpement have recently been identified as prognostic marker in the resolution of hallucinations in children. The first objective of this work is to provide a reliable assessment or early-onset hallucinations, the underlying objective is to allow longitudinal assessment of this symptom in children and adolescents and to better adapt its therapeutic. Finally, we are interested in the development of an innovative therapy in children and adolescents, which is the repetitive trancranial magnetic stimulation (rTMS). This neuromodulation technique has the advantage to target a symptom, not a disease, and can therefore be applied to a number of hallucinated subjects.The objective of this work was to study early-onset hallucination through diverse approaches facilitating the trust of the child and both phenomenological and cognitive caracterisation of the symptom by the clinician.The results gathered in this PhD work demonstrate that it is possible to understand the early-onset hallucinatory symptoms through cognition and new technologies. These approaches allow us to adapt our daily practice, gives us a better understanding of the symptoms and associated cognitive mechanisms, thereby improving our therapeutic management
Bourseau, Erika. "De la compréhension du comportement des cellules initiatrices de cancer dans les glioblastomes au développement d'une nanomédecine adaptée. Focalisation sur le marqueur de cellules souches cancéreuses AC133 / CD133." Phd thesis, Université d'Angers, 2011. http://tel.archives-ouvertes.fr/tel-00662253.
Rakotomalala-Andrianasolo, Andria. "Développement et caractérisation de modèles cellulaires pour l'étude du rôle de l'oncohistone H3.3 K27M dans le phénotype agressif et la réponse aux thérapies des gliomes pédiatriques diffus de la ligne médiane." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS015.
H3K27-altered DMG treatment is one of the most significant challenges in pediatric neuro-oncology,with no improvement in patient survival over the past 50 years. In 2012, it was shown that DMGs harbor a specific histone 3 mutation (oncohistone) called H3.3 K27M with a very high prevalence (70-80% of cases). Although theH3.3 K27M impact on the epigenetic landscape has been well described, studies are needed to understand betterits role in DMG cells’ aggressiveness and response to therapies.To study the H3.3 K27M mutation impact on DMG cell phenotypes precisely, we developed andcharacterized pediatric high-grade glioma isogenic cellular models induced and knock-out for the oncohistone.Using these models, we aimed to decipher the oncohistone impact on DMG cell biology and response to anticancertherapies, including radiation therapy, the only current standard of care for DMGs. Characterization of our H3.3 K27M-induced pediatric supratentorial glioma cell lines reveals that the oncohistone affects the response to ionizing radiations and specific targeted therapies in a cellular context-dependentway. Based on these results, we settled to characterize oncohistone biological impacts in a more relevant cellular context of DMG. In that sense, we established H3.3 K27M knock-out cellular models and characterized them regarding their parental DMG H3.3 K27M mutated cell lines. Through omic (transcriptomic and proteomic)and cell metabolism characterizations of these models, we notably showed the H3.3 K27M mutation impact on DMG cells’ lipid metabolism. In 3D spheroid models, this H3.3 K27M-induced lipid metabolism rewiring appeared conditioned by microenvironment factors still under investigation.On the other hand, a functional pharmacological screen identified H3.3 K27M-driven dependencies tospecific DNA repair pathways. In addition, ongoing radiobiological characterization of our models indicates anH3.3 K27M-associated radiosensitivity correlating with a decrease in DNA repair efficiency following ionizingradiations. Beyond this DNA repair impact, our pharmacological screen also revealed an H3.3 K27M-relatedsensitivity to cardiac glycoside drugs. This result makes sense with our transcriptomic data showing enrichmentin genes involved in cardiomyopathies and ion homeostasis among differentially expressed genes with theoncohistone. In this context, we began unraveling the molecular and biological processes underlying thisH3.3 K27M-driven effect.Finally, we used our isogenic cellular models to show that the H3.3 K27M oncohistone drives lipidmetabolism modifications. These metabolic changes could prime H3K27-altered DMG cells to specific regulatedcell death pathways (e.g., ferroptosis) and affect the response to certain therapies. Moreover, the H3.3 K27Mseems to drive specific sensitivities, notably to radiation therapy and cardiac glycoside drugs. Understanding the underlying molecular mechanisms governing these H3.3 K27M-associated Achille heels could highlight newinsights into the oncohistone role in DMG cells and provide rationales for developing new therapeutic strategies
Tiran-Cappello, Alix. "Rôle du noyau subthalamique et de ses afférences hyperdirectes provenant du cortex préfrontal dans le codage et la recherche de récompense chez le rat." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0448/document.
Deep brain stimulation (DBS) is currently one form of effective treatment for Parkinson’s disease. This approach is currently considered for the treatment of addiction. It consists in the delivery of small electric impulses inside a brain structure: the subthalamic nucleus. We have shown in the subthalamic nucleus the existence of signature associated with the transition to addiction and compulsive drug abuse, as well as the therapeutic potential of DBS to reduce pathological intake and compulsive cocaine abuse in rats. We also established the specific control exerted by the subthalamic nucleus on the motivation for sweet food and drug of abuse. Overall this thesis could allow a better understanding of the mechanisms of DBS, its therapeutic potential in addiction and possible side effects
Péron, Sophie. "Évaluation du potentiel thérapeutique des stratégies de remplacement cellulairedans un modèle de lésion corticale chez la souris : transplantation neuronale etmobilisation des cellules souches endogènes." Thesis, Poitiers, 2013. http://www.theses.fr/2013POIT2254/document.
Damage to the adult motor cortex can lead to severe deficits in motor function. One strategy for overcoming the generally limited capacity of the mature central nervous system to regenerate axons in response to cell loss is cell replacement based therapies. We studied brain repair strategies in a mouse model of motor cortex aspiration lesion by using transplantation of embryonic neurons or stem cells-derived neurons and by evaluating the potential of endogenous stem cells found in the subventricular zone. Neuronal transplantation efficacy depends on the capacity of the transplanted cells to developp into appropriate neuronal phenotype and establishment of specific connections. We have shown that embryonic cells grafted immediately after lesion into the lesioned motor cortex develop into mature neurons with appropriate phenotype and establish projections towards appropriate targets. We have shown that introducing a delay of one week between motor cortex lesion and transplantation enhances graft vascularization, grafted cells proliferation and the density of transplant-to-host projections. Besides, we have studied the possibility to generate cortical neurons from human stem cells as an alternative source of neurons for transplantation. Finally, recruitment of endogenous stem cells found in the SVZ was examined in a mouse model of cortical lesion. We have shown that motor cortex injury increases cellular proliferation and neurogenesis in the SVZ and the migration of neuroblasts near the lesion site via blood vessels and astrocytes assisted migration
Cicero, Julien. "TrkA dans les métastases cérébrales des cancers du sein triple négatifs." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS031.
Nearly 90% of deaths in breast cancer patients are due to metastasis. Triple-negative(TN) breast cancer is characterized by its aggressive nature and high propensity to metastasize. Among the various sites of metastasis, the development of brain metastasis is associated with the worst prognosis, with a greater impact on patients'quality of life. The mechanisms underlying the progression of brain metastases in triplenegativebreast cancer are incompletely understood. To address this gap, we have used several experimental models to study the behavior of breast cancer cells during the process of dissemination to the brain. These models include an in vitro human blood-brain barrier (BBB) model, in vitro 3D organotypic extracellular matrix, ex vivo co-cultures of mouse brain slices, and in vivo xenograft experiments. By recapitulating the final key steps of brain metastasis in these models, we sought to better understand the underlying molecular mechanisms. In this work, we demonstrate the involvement of TrkA and its co-receptors (e.g. EphA2) in the development of brain metastases. First, we identified the TrkA/EphA2 receptor complex as a mediator of proNGF-induced BBB transmigration. Furthermore, our results showed that combined inhibition of TrkA and EphA2 significantly reduced brain metastasis in a preclinical breast cancer model. These results challenge the current understanding of the mechanisms of brain metastasis and highlight the role of proNGF as a key factor in the brain tropism of metastatic TN breast cancer
Proulx-Bonneau, Sébastien. "Signaletic partners of MT1-MMP in hypoxic mesenchymal stem cells and survival functions in glioblastoma multiform cells." Mémoire, 2011. http://www.archipel.uqam.ca/4235/1/M12168.pdf.
Marcotte, Karine. "Intervention orthophonique et neurobiologie du cerveau : apports de la neuroimagerie à la prise en charge de l’aphasie chronique." Thèse, 2011. http://hdl.handle.net/1866/6092.
Aphasia is an acquired language impairment leading to communication disorders which may affect comprehension and/or expression. When aphasia follows a stroke, major recovery of the communicative deficits is initially observed after the lesion, but for some the aphasia may remain severe and is considered to be chronic after a year. Furthermore aphasia can be observed in primary progressive aphasia, a degenerative disease only affecting language in the early years. The impact of therapy in chronic aphasia is the subject of growing literature in recent years and has shown language improvements after several years of therapy. The left hemisphere seems to have a crucial role and is associated with greater language improvements but our understanding of brain plasticity mechanisms is still lacking. In primary progressive aphasia, few studies have examined therapy effectiveness. Using functional magnetic resonance imaging, the aim of these studies was to examine therapy-induced brain plasticity mechanisms following Semantic Feature Analysis in ten participants suffering from chronic aphasia and one participant with primary progressive aphasia. The results suggest that brain reorganization is possible several years after injury and in degenerative disease. At the individual level, greater language improvement is associated with the recruitment of the left hemisphere and less activated areas. Group analysis shows the recruitment of left inferior parietal lobule, whereas the activation of left precentral gyrus predicts improved response to therapy. Functional connectivity analysis allowed for the first time the identification of the default-mode network in aphasia. Following therapy, the integration of this well-known network is comparable to that of the controls and the correlation analysis suggests that the default-mode network integration has a predictive value for improvement. Therefore, the results of these studies support the idea that the left hemisphere has a major role in the recovery of aphasia and provide evidence on therapy-induced neuroplasticity in aphasia. In addition, the identification of key areas and networks will guide future research in order to possibly maximize the recovery of aphasia and to better predict the prognosis.