73 research outputs found
Vehicle-mounted shields and low trackside barriers for railway noise control in a European context
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Pathological markers and therapeutic prospects in Sporadic Amyotrophic Lateral Sclerosis
No full textLa sclérose latérale amyotrophique (SLA) sporadique est une pathologie neurodégénérative affectant les motoneurones, responsable d’une paralysie diffuse d’aggravation rapidement progressive aboutissant au décès des patients dans les 5 années suivant le diagnostic. Il n’existe à ce jour aucun traitement de la maladie. L’étude des lésions neuronales à l’origine de la maladie, l’identification de biomarqueurs de la SLA, et la mise au point de nouvelles approches thérapeutiques sont les domaines de recherche sur lesquels les efforts sont actuellement concentrés. Le premier objectif de ce travail de thèse a été d’optimiser l’analyse histologique des lésions neuronales observées chez les patients atteints de maladies neurodégénératives grâce à l’utilisation des nouvelles techniques d’imagerie super-résolutive, qui permettent un immunomarquage spécifique à l’échelle nanoscopique. Nos premiers résultats obtenus à partir de la banque de cerveaux du département de Neuropathologie du CHU d’Angers ont permis de caractériser avec précision les agrégats protéiques observés dans les processus de neurodégénérescence, ouvrant un nouveau champ pour l’exploration du tissu cérébral et médullaire des patients atteints de SLA. Le second travail de cette thèse a porté sur l’identification de biomarqueurs de la SLA à partir des hypothèses physiopathologiques impliquant la protéine TDP-43, des déficits mitochondriaux et les anomalies du cytosquelette. Grâce à l’expertise de l’équipe MitoLab (Angers), nous avons exploré l’ultrastructure cellulaire, le métabolisme énergétique et protéique, l’architecture du réseau mitochondrial, et la réponse au stress d’une biocollection de fibroblastes issue de patients atteints de SLA sporadique constituée prospectivement. Nos données ont permis d’objectiver une altération de certaines voies métaboliques, ainsi qu’une augmentation de la synthèse du collagène. Ces résultats font de ces deux paramètres de potentiels marqueurs diagnostique et pronostique de la maladie. La 3ème approche expérimentale de cette thèse a été menée au sein de l’équipe du Professeur J.-P. JULIEN (Institut CERVO Canada). Nous avons étudié l’adressage et l’action d’anticorps ciblant les agrégats de protéine TDP-43 au niveau du système nerveux central. Nos résultats obtenus par immunomarquages fluorescents et études histologiques ont montré l’efficacité de l’adressage du traitement ainsi qu’une diminution des lésions chez des souris transgéniques porteuses de la mutation TDP-43A315T. Sur la base de ces résultats, des projets complémentaires ont été initiés dans la perspective de tester l’efficacité cette nouvelle approche chez l’homme.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons.The disease is responsible for a progressive paralysis leading to death within 5 years after the symptom onset, with no curative treatment available so far. Studying pathophysiological processes, identifying new biomarkers of the disease, and developing new therapeutic prospects are currently the three main fields of ALS research. In this work, we first aimed to develop a new microscopy technique allowing super-resolutive imaging of the human brain, with the aim of studying tissue samples at the nanoscale level with specific immunostaining. Our results on brain samples from the Neuropathology Department of the University Hospital of Angers allowed us to characterize precisely the architecture of pathological protein aggregates observed in neurodegenerative disorders. Extending this approach to brain and spinal cord samples from patients affected with ALS will contribute to characterize the composition and organization of intra-neuronal lesions, and reveal underlying mechanisms involved in the diseases. Concomitantly, we aimed to identify new ALS biomarkers on the basis of pathophysiological mechanisms involved in the disease. Thanks to the expertise of the research unit MitoLab (Angers), we analyzed the ultrastructural organization, mitochondrial metabolism, stress response and collagen synthesis of controls- and patients derived skin fibroblasts. Our results highlighted alterations of purine and pyrimidine metabolisms, and an increase of the collagen synthesis in fibroblasts derived from ALS patients. These parameters could be used as markers for ALS diagnosis and prognosis, and may turn out to be valuable tools in clinical practice and therapeutic research. Finally, joining the Canadian research team of Pr Jean-Pierre JULIEN (CERVO Institute, Qc), we participated in the development of a new therapeutic approach in ALS based on the use of monoclonal antibodies targeting pathological TDP-43 aggregates in neurons. The treatment decreased TDP-43 proteinopathy in vitro in cultured neuronal cells, and in vivo in TDP-43A315T transgenic mice models. On the basis of these results, a new research project has started with the aim of humanizing the antibodies to consider immunotherapy for future therapeutic trial
Hereditary amyloid neuropathy by transthyretin Val107 mutation in a patient of African origin
No full textInternational audienc
Interferometric modeling of wave propagation in inhomogeneous elastic media using time reversal and reciprocity
No full textTime reversal of arbitrary, elastodynamic wavefields in partially open media can be achieved by measuring the wavefield on a surface surrounding the medium and applying the time reverse of those measurements as a boundary condition. We use a representation theorem to derive an expression for the time-reversed wavefield at arbitrary points in the interior. When this expression is used to compute, in a second point, the time-reversed wavefield originating from a point source, the time-reversed Green’s function between the two points is observed. By invoking reciprocity, we obtain an expression that is suitable for modeling of wave propagation through the medium. From this we develop an efficient and flexible two-stage modeling scheme. In the initial phase, the model is illuminated systematically from a surface surrounding the medium using a sequence of conventional forward-modeling runs. Full waveforms are stored for as many points in the interior as possible. In the second phase, Green’s functions between arbitrary points in the volume can be computed by crosscorrelation and summation of data computed in the initial phase. We illustrate the method with a simple acoustic example and then apply it to a complex region of the elastic Pluto model. It is particularly efficient when Green’s functions are desired between a large number of points, but where there are few common source or receiver points. The method relies on interference of multiply scattered waves, but it is stable. We show that encoding the boundary sources using pseudonoise sequences and exciting them simultaneously, akin to daylight imaging, is inefficient and in all explored cases leads to relatively high-noise levels
Chronic inflammatory demyelinating polyneuropathy in Waldenström's macroglobulinemia
No full textWaldenström’s disease (WD) is frequently associated with a predominantly sensory neuropathy with a progressive course due to the monoclonal IgM activity against Myelin Associated Glycoprotein (MAG). However, neurolymphomatosis or chronic demyelinating inflammatory polyneuropathy (CDIP) may occur in some patients with WD.Case report We report a case of Waldenström’s macroglobulinemia in an adult male presenting with cranial nerve palsy and rapidly progressive asymmetric polyneuropathy. Intravenous IgM treatment that provided transient amelioration was followed by a relapse involving tetraparesis. Cerebrospinal fluid analysis, medullar magnetic resonance imaging, and electrophysiological studies led to equivocal findings suggesting the presence of either neurolymphomatosis or CIDP. Finally, sural nerve biopsy results supported the diagnosis of CIDP, which then received appropriate treatment. Conclusion In patients with WD, the possible occurrence of CIDP should be investigated with a neuromuscular biopsy when other investigations are equivocal since the disease calls for a specific treatment
Disease status in chronic inflammatory demyelinating polyneuropathy: inter‐centre comparative analysis and correlates
No full textA comparative study elucidating the substantial functional defects of electroporated T cells relative to a mechanical SQZ-based approach
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