Un certain nombre d'essais cliniques contrôlés, randomisés et publiés récemment en littérature a démontré que la thrombectomie mécanique, offerte aux patients présentant un AVC ischémique aigu, est liée à une meilleure évolution clinique en comparaison au traitement standard de fibrinolyse intraveineuse. Les stents retriever ont été reconnus dans ces essais comme les dispositifs les plus efficaces pour la thrombectomie intracrânienne. Actuellement, toutes les industries produisant des dispositifs neuro-interventionnels lancent sur le marché un nombre croissant de stents retriever. Chaque nouveau dispositif proposé est censé avoir une particularité permettant de meilleures performances par rapport aux dispositifs déjà disponibles sur le marché. Néanmoins, aucune étude clinique n’a démontré, jusqu'à présent, la supériorité en termes de résultats anatomiques et cliniques d'un stent retriever donné. En outre, le mécanisme d'interaction entre les stents retriever et le thrombus n'a pas été évalué jusqu'ici de façon exhaustive. Dans la présente étude, nous avons analysé expérimentalement les performances de tous les stents retriever disponibles sur le marché français jusqu'à juin 2015. Le but de cette étude était d'identifier toutes les caractéristiques des dispositifs fonctionnels à la capture du thrombus. Chaque dispositif a été évalué par des tests mécaniques et fonctionnels : les tests mécaniques ont été effectués afin d'étudier la force radiale des dispositifs. L'objectif était d'évaluer la force radiale exercée par le stent dans deux conditions spécifiques : lors du déploiement et pendant le retrait.Les tests fonctionnels ont visé à évaluer visuellement la capacité du stent à rester en apposition sur la paroi des vaisseaux et à maintenir le thrombus à l'intérieur de ses mailles au cours du retrait. Nous avons évalué l'interaction des dispositifs avec thrombus de taille et de caractéristiques différentes que nous avons générées en utilisant du sang humain afin d'obtenir deux types de caillot : un souple « de type rouge » composé par tous les éléments du sang et un dur « de type blanc» qui a été principalement composé de plasma riche en plaquettes. Ces essais ont été effectués en utilisant un modèle vasculaire rigide reproduisant la circulation cérébrale antérieure. Deux neuro-interventionnels ayant une expérience dans les procédures de thrombectomie ont effectué les tests fonctionnels. Chaque expérience a été filmée et deux auteurs par la suite ont effectué une analyse visuelle des résultats.Les essais mécaniques ont montré un comportement différent en termes de variation de pression radiale au cours du retrait pour chaque stent. Une pression radiale constante pendant le retrait est liée à une cohésion constante sur la paroi artérielle pendant le retrait, avec un taux plus important de retrait du caillot. Tous les stents retriever glissent sur le caillot blanc de grande taille (diamètre>6 mm) ayant un très bas taux d’efficacité en termes de retrait. / A number of randomized controlled trials recently appeared in literature demonstrated that early mechanical thrombectomy offered to patients presenting with acute ischemic stroke is related to improved functional outcome in comparison to standard care intravenous fibrinolysis. Stent retrievers have been recognized in these trials as the most effective devices for intracranial thrombectomy. Currently, all industries producing neuro-interventional devices are launching into the market an increasing number of stent-based retriever tools. Each new device proposed for clinical use is supposed to have peculiar features allowing better performances in comparison to devices already available for clinical practice. Nevertheless, none clinical study has demonstrated so far the superiority, in terms of anatomical and clinical results, of a given stent retriever device. Furthermore, the mechanism of interaction between stent retrievers and thrombi has not exhaustively evaluated so far. In the present study we experimentally analyzed performances of all stent retrievers available into the French market up to Juin 2015. The aim of this study was to identify any device feature that was functional to the thrombus removal.Stent retrievers were evaluated by mechanical and functional test: mechanical tests were performed in order to investigate devices radial force, the aim was to evaluate the radial force exerted by the stent in two specific conditions: upon deployment and during the retrieval.Functional tests were aimed to visually evaluate the stent retriever’s ability in remaining in close apposition to the vessels wall and to maintain the thrombus engaged within its struts during the retrieval. We evaluated the interaction of the devices with thrombi of different features and sizes that we generated using human blood in order to obtain two types of clot: one softer “red type” that was composed by all elements of the whole blood and one stiffer “white type” that was mainly composed by platelet-rich plasma. Such tests were conducted using a rigid 3D printed vascular model reproducing the brain anterior circulation. Two neuro-interventionalists with experience in thrombectomy procedures performed functional tests, each experiment was filmed and two authors thereafter conducted visual analysis of the results.Mechanical tests showed different behavior in terms of radial pressure variation during retrieval for each stent. Constant radial pressure during retrieval was related to constant cohesion over the vessel wall during retrieval and higher rate of clot removal efficacy. All stent retrievers slide over the clot failing in clot removal when interact with white large thrombi (diameter>6 mm).

Objetivos A estimulação magnética transcraniana (TMS, do inglês: Transcranial Magnetic Stimulation) e as imagens funcionais por ressonância magnética (fMRI, do inglês: functinal Magnetic Resonance Imaging) são duas técnicas não invasivas de investigação de atividade do sistema nervoso central. Porém essas duas técnicas utilizam estratégias diferentes para mensurar a atividade cerebral, sendo que a TMS avalia a resposta elétrica enquanto que a fMRI a resposta hemodinâmica. Nosso intuito nesse trabalho foi criar ferramentas para a comparação dessas duas técnicas no mapeamento do córtex motor, bem como utilizando as ferramentas desenvolvidas, fazer uma comparação dos mapas motores de pacientes com AVC com sujeitos assintomáticos, e nesses dois grupos, também realizar uma avaliação nos efeitos no córtex motor da eletroestimulação sensorial (SES, do inglês: Sensory Electric Stimulation) pelas técnicas de TMS e fMRI. Métodos Paro o mapeamento vetorial do campo magnético produzido pela bobina de TMS utilizamos fantomas que simulavam o tecido cerebral e realizamos medidas de imagens de ressonância magnética (MRI, do inglês: Magnetic Resonance Imaging) de fase em três direções para a construção do mapa vetorial. Uma vez dominada a técnica de mapeamento por imagens de fase, a utilizamos para auxiliar na construção de bobinas para estimulação periférica e pequenos animais. Para realização do mapeamento do córtex motor com TMS desenvolvemos um sistema de neuronavegação (Neuronavegador InVesalius) e um programa para análise dos sinais de eletromiografia (MEPHunter), bem como um segundo programa para fazer o corregistro dos mapas de produzidos pela TMS com os mapas de fMRI (TMSProjection). Em posse dessas ferramentas, pudemos realizar o mapeamento do córtex motor de pacientes com AVCi crônicos. Para tanto estimulamos uma área quadrada de 25cm2 do escalpo sobre o córtex motor e coletamos o potencial evocado nos músculos abdutor curto do polegar ipsi e contralateral à TMS, e nos músculos flexor e extensor radial do carpo, contralaterais à TMS. Para a realização das fMRIs realizamos um paradigma evento-relacionada com um protocolo de abrir e fechar a mão. Por fim avaliamos os efeitos da SES à 3Hz com um única sessão de 30 minutos, realizando medidas de potencial evocado e fMRI imediatamente antes e imediatamente após à SES. Resultados O sistema de neuronavegação juntamente com o conjunto de programas computacionais possibilitou a realização dos estudos clínicos. Nossos dados mostraram uma correlação maior entre os mapas de MEP e os mapas de fMRI nos sujeitos normais do que nos pacientes com AVC, principalmente no hemisfério afetado. Nossos resultados também sugerem que a SES pode provocar modulação na excitabilidade cortical, causando redução da excitabilidade cortical das regiões motoras, quando aplicados na frequência e duração utilizadas nesse estudo. Conclusão O mapeamento de campo magnético por MRI é uma boa alternativa para medir campos complexos e pode ser utilizado no desenvolvimento de novas bobinas de estimulação magética. O neuronavegador Invesalius, o MEPHunter e o TMSProjection são ferramentas poderosas para estudos em neuroimagens podendo ser ampliado seu uso para outras áreas como neurologia e fisioterapia. Quanto aos estudos clínicos acreditamos que o fator que mais colabora para a pior correlação dos mapas dos pacientes é a redução de fibras corticoespinhais e a plasticidade, e que a SES aplicada a 3Hz em uma única sessão tem um efeito agudo de redução da excitabilidade do córtex motor. / Background and Purpose - Transcranial magnetic stimulation (TMS) and functional magnetic resonance images (fMRI) are two noninvasive techniques to investigate the central nervous system activity. These two techniques use different strategies to measure brain activity, once the TMS evaluates the electrical response while the fMRI studies hemodynamic response. Our purpose in this study was to create tools for the comparison of these two techniques for mapping the motor cortex. Latter, using these tools, we compared the motor maps of stroke patients and healthy subjects. Furthermore, we evaluated the effects of electrical stimulation in the sensory motor cortex (SES) by TMS and fMRI techniques. Methods - In order to map the magnetic field vector produced by the TMS coil, we used phantoms that simulated brain tissue and performed measurements of magnetic resonance phase images in three directions, in this way, composing the vector map. Then, we used this technique for helping to build small coils for peripheral and small animals stimulation. For the TMS mapping, we developed a neuronavigation system (InVesalius neuronavigator) and a program to analyze the electromyogram responses (MEPHunter). Secondly, a program to co-register the TMS and fMRI maps (TMSProjection) was created. Using these tools, we mapped the motor cortex of the chronic ischemic stroke patients. For this, we stimulated a square scalp area of 25cm2 over the motor cortex and collected the motor evoked potential (MEP) in the abductor pollicis brevis, ipsilateral and contralateral to TMS, and the flexor and extensor carpi radialis, contralateral to TMS. FMRI was also acquired using an event-related paradigm where the volunteers were asked to open and close their hand. Finally, we evaluated the effects of 3Hz SES in a single 30-minute session, performing measurements of TMS and fMRI before and immediately after the SES. Results - The neuronavigation system and the developed softwares made possible clinical studies. We also found a higher correlation between the MEP and fMRI maps in normal subjects than in stroke patients, especially in the affected hemisphere. Additionally, Our results suggested that SES may cause reduction in cortical excitability of motor regions, when applied with the frequency and duration used in this study. Conclusion - The magnetic field MRI mapping is an efficient alternative for complex fields measuring and can be utilized in the development of new TMS coils geometry. The neuronavigator InVesalius, MEPHunter and TMSProjection are powerful tools for neuroimaging studies and other areas as neurology and physiotherapy. We believe that the most important factor that contributes to the correlation decrease between the MEP and fMRI maps of the patients is the reduction of functional corticospinal fibers and the plasticity of motor areas. In this sense, the 3 Hz SES showed to be a potential technique as therapy in spastic patients.

Introdução: A desnutrição é um problema de saúde frequente, especialmente em pacientes com AVC, que atinge cerca de 16% da população podendo aumentar para 50% em até 3 meses. A Disfagia orofaríngea é considerada um distúrbio de deglutição, com sinais e sintomas específicos, que se caracteriza por alterações em qualquer etapa e/ou entre as etapas da dinâmica da deglutição, podendo ocorrer em 45 a 65% dos casos de AVC. Desnutrição e problemas de deglutição são comuns após acidente vascular encefálico e frequentemente ocorrem juntos. A falha em reconhecer a sua presença resultará em um aumento da morbidade e mortalidade. Pacientes internados em hospital como consequência de um AVC podem já estar desnutridos ou em risco de desnutrição, e muitas vezes estes se tornam mais desnutridos enquanto estão hospitalizados, mantendo este quadro meses depois. Entretanto, apesar da alta taxa de morbidade e mortalidade, estudos que investigam a evolução da desnutrição e disfagia e suas consequências clínicas após a o AVC ainda são escassos. Objetivos: Este estudo tem como objetivos identificar a frequência do estado nutricional e as dificuldades de deglutição em pacientes com AVC além de identificar os fatores preditivos para o estado nutricional e verificar se há associação entre o estado nutricional e os desfechos clínicos nesta população após três meses do ictus. Casuística e Métodos Foram avaliados 102 pacientes com AVC que deram entrada na Unidade de Emergência e que compareceram para consulta no Ambulatório de Doenças Neurovasculares (ADNV) do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRPUSP) após três meses do ictus. Os seguintes procedimentos foram realizados com todos os pacientes selecionados para o estudo: aplicação da NIHSS para avaliação da gravidade do AVC; escala de Rankin modificada, para avaliação da capacidade funcional; aplicação do Eating Assessment Tool (EAT-10) que avalia sintomas de disfagia; aplicação da Mini-Avaliação Nutricional (MNA®) para avaliação do estado Nutricional e avaliação da cognição com o Mini Exame do Estado Mental (MEEM) Resultados: De acordo com a Análise multivariada (Correlação de Pearson) entre os instrumentos de avaliação é possível determinar que o estado nutricional associou-se com a gravidade do AVC na admissão (r=-0,38; p=0,001) e ambos se correlacionaram com incapacidade funcional aos 3 meses (r=-0,5; p=0,001), (r=0,45; p=0,001). A gravidade do AVC na admissão associou-se significativamente com maior número de noites no hospital. (r=0,41 p=0,001). E que a presença de alteração cognitiva associou-se significativamente com a incapacidade funcional aos 3 meses (rankin de 3 meses) (r=-0,51; p=0,001). Na análise de regressão logística, utilizando o método Backward a gravidade do AVC na admissão hospitalar foi fator preditivo independente de desnutrição nesta população (p=0,001) Portanto, os pacientes com pior estado nutricional possuíam maior gravidade do AVC na admissão, tiveram maior tempo de internação, (noites no hospital) e possuíam pior capacidade funcional e pior cognição aos 3 meses. / Introduction: Malnutrition is a frequent health problem, especially in patients with stroke, which affects about 16% of the population and can increase to 50% within 3 months. Oropharyngeal dysphagia is considered a swallowing disorder, with specific signs and symptoms, which is characterized by changes at any stage and / or between the stages of swallowing dynamics which can occur in 45 to 65% of stroke cases. Malnutrition and swallowing problems are common after a stroke and often occur together. Failure to recognize their presence will result in increased morbidity and mortality. Patients hospitalized as a consequence of a stroke may already be malnourished or at risk of malnutrition and often become more malnourished while hospitalized, maintaining this condition months later. However, despite the high rate of morbidity and mortality studies that investigate the evolution of malnutrition and dysphagia and its clinical consequences after stroke are still scarce. Objectives: This study aims to identify the frequency of nutritional status and swallowing difficulties in stroke patients in addition to identifying the predictive factors for nutritional status and to verify if there is an association between nutritional status and clinical outcomes in this population after three months of the stroke. Casuistry and Methods: We evaluated 102 stroke patients admitted to the Emergency Unit and attending the Neurovascular Diseases Outpatient Clinic (ADNV) at the Hospital das Clínicas of the Medical School of Ribeirão Preto at the University of São Paulo (HCFMRP-USP) After three months of the stroke. The following procedures were performed with all patients selected for the study: application of the NIHSS to evaluate the severity of stroke; Modified Rankin scale for functional capacity assessment; Application of the Eating Assessment Tool (EAT-10) evaluating symptoms of dysphagia; Application of the Nutritional Mini-Assessment (MNA®) to evaluate the nutritional status and evaluation of cognition with the Mini Mental State Examination (MMSE). Results: According to the Multivariate Analysis (Pearson\'s Correlation) among the evaluation instruments it was possible to determine that the nutritional status was associated with the severity of stroke on admission (r = - 0.38, p = 0.001) and both Correlated with functional disability at 3 months (r = -0.5, p = 0.001), (r = 0.45, p = 0.001). The severity of stroke on admission was significantly associated with greater number of nights in the hospital. (R = 0.41 p = 0.001). And that the presence of cognitive alteration was significantly associated with functional disability at 3 months (Rankin of 3 months) (r = -0.51; p = 0.001). In the logistic regression analysis using the Backward method the severity of stroke at hospital admission was an independent predictor of malnutrition in this population (p = 0.001). Therefore, patients with worse nutritional status had a greater severity of stroke on admission, had a longer (Nights in the hospital) and had worse functional capacity and worse cognition at 3 months.

En France, on estime à 150 000 le nombre d’accident vasculaire cérébraux par an. Avec un coût de 8,3 milliards d’euros, c’est devenu une problématique de santé publique. Les dépenses sont, entre autres, lié aux séquelles, car 43,2 % sortent d’hospitalisation en étant dépendant physiquement.Ces séquelles vont séquelle vont être à l’origine de limitations, provoquant un cercle vicieux d’inactivité, et amenant un déconditionnement. Pour lutter contre ce déconditionnement, il semble pertinent de respecter les recommandations des sociétés savantes en termes d’activité physique (AP). Néanmoins en retour à domicile, très peu de patients atteignent le minimum d’AP requis. L’éducation thérapeutique du patient (ETP) semble être une option pertinente pour remédier à ce problème.Ce travail de recherche s’est donc intéressé à l’effet d’un programme ETP à l’AP chez des patients en phase subaigue. Le programme était effectué au domicile des patients, et était composé de visites à domicile et d’appels téléphoniques. L’AP était contrôlée grâce à un actimètre et des livrets de suivi.Après les 6 mois du programme, il ressort une augmentation du périmètre de marche, mais pas d’impact sur la force des membres inférieurs, la composition corporelle, la fatigue et la dépression.Les principales caractéristiques des patients volontaires à un programme ETP à l’AP étaient la persistance de la fatigue, la dépression, peu de séquelles neuro-motrices physiques et un fort soutien de l’entourage. Enfin, au cours des 6 mois de suivi, les patients ont maintenu des durées d’AP qui étaient au-dessus des recommandations en termes d’AP. / In France, we estimate at 150,000 the number of cerebral vascular accident per year. With a cost of 8.3 billion euros, it has become a public health issue. The expenses are, among others, related to legacy, as 43.2% leave hospital being physically dependent.These effects will aftereffect will cause limitations, causing a vicious cycle of inactivity and deconditioning bringing. To fight against this deconditioning, it seems appropriate to follow the recommendations of learned societies in terms of physical activity (PA). Yet back home, very few patients reach the minimum required AP. Therapeutic patient education (TPE) seems to be a relevant option to address this problem.This research is therefore interested in the effect of ETP to the AP in patients with subacute phase. The program was conducted in patients' homes, and consisted of home visits and phone calls. The PA was controlled through a actimeter and monitoring booklets.After 6 months of the program, it appears an increase in the walking distance, but no impact on the strength of lower limbs, body composition, fatigue and depression.The main characteristics of volunteer patients to ETP to the PA were persistent fatigue, depression, few physical neuro-motor sequelae and strong support from the entourage.Finally, during the 6 months follow-up, patients maintained durations of AP which were above recommendations in terms of AP.

L’accident vasculaire cérébral (AVC) ischémique est une principale cause de décès et d’handicap en Europe. L’éthanol est une drogue largement consommée et la consommation chronique d’éthanol est un facteur participant à la survenue d’AVC ischémique (Reynolds et al., 2003). La consommation chronique et excessive d’éthanol est associée à un risque accru de mortalité et de morbidité suite à un AVC ischémique (Zhang et al., 2014). Ce facteur aggraverait les lésions ischémiques cérébrales dans les modèles animaux (Zhao et la 2010 ; Lemarchand et al., 2015). Le stress oxydatif et l’excitotoxicité glutamatergique peuvent jouer un rôle important dans l’exacerbation de l’infarctus cérébral après une consommation chronique et excessive d’éthanol (Zhao et la 2010 ; Zhao et la 2011). Le premier objectif de la thèse est de vérifier que la consommation chronique et excessive d’éthanol aggrave les dommages cérébraux ischémiques chez les patients et dans un modèle animal d’ischémie cérébrale. Le deuxième objectif est d'étudier l'inflammation post-ischémique dans le cerveau et dans le foie à court et moyen termes. Des rats mâles Wistar ont été soumis à l'administration chronique d'éthanol (10% ou 35% v/v, 5 ml / kg, deux fois par jour, quatre semaines avant l'opération) ou d’eau (vehicule), suivie d’une occlusion de l'artère cérébrale moyenne (OACM). Nous avons déterminé les effets de l'ingestion d’éthanol sur le volume de l'infarctus, des déficits neurologiques et moteurs, à 24 heures (J1) et à 7 jours (J7) de reperfusion sanguine. Nous avons quantifié le nombre de microglies activées dans l'hémisphère ipsilatéral. Nous avons mesuré le nombre de neutrophiles et les taux d’ARNm d’ICAM-1 et de VCAM-1 dans l'hémisphère ipsilatéral et dans le foie. Nous avons examiné la stéatose et l'état inflammatoire dans le foie des rats non ischémiés, pour évaluer l'état physiologique hépatique dans les 3 groupes à J1 et J7. Nous avons recruté 435 patients ayant eu une ischémie cérébrale supratentorielle dans les 48 heures après l'apparition des symptômes. La consommation excessive et chronique d’éthanol est définie par une prise hebdomadaire ≥300 g d'éthanol et les AVC ischémiques sévères par un score National Institutes of Health Stroke Scale (NIHSS) ≥6. Le score NIHSS a été évalué dans les 48 heures. Nous avons effectué des mesures des taux de transferrine déficiente en carbohydrates (CDT, biomarqueur de la consommation chronique excessive d'éthanol) et de marqueurs inflammatoires. Être un consommateur excessif et avoir un taux plasmatique élevé de neutrophiles étaient indépendamment associés à des déficits neurologiques plus sévères chez les patients ayant subi un AVC ischémique ou accident ischémique transitoire, dans les 48 heures. La consommation excessive et chronique d'éthanol chez le rat non ischémié a induit une stéatose hépatique et une augmentation d'un état inflammatoire dans le cortex, le striatum et le foie par l'intermédiaire d'augmentation de l'expression de protéines d'adhésion. Toutefois, aucune infiltration des neutrophiles n’a été notée dans le foie ou dans le cerveau. Dans le modèle OACM, la consommation chronique d’éthanol 35 ° aggravait le volume des lésions de l'AVC ischémique et les déficits moteurs, comparativement aux rats non exposés à l’éthanol. L'aggravation des déficits neurologiques et fonctionnels a été expliquée par une augmentation de l'inflammation post-ischémique dans le foie et le cerveau, via l'activation de la microglie, l’infiltration des neutrophiles, et l’expression des protéines d’adhésion leucocytaire à court et moyen termes. / Ischaemic 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.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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O Acidente Vascular Cerebral (AVC) é uma doença prevalente e incapacitante, cujo atendimento no Brasil é insuficiente e concentrado em poucos centros de alta complexidade. A telemedicina possibilita assistência à saúde através do uso de tecnologias de comunicação entre dois ou mais profissionais, ou entre o profissional e o paciente, que estejam em locais distintos, permitindo aumento do acesso a tratamentos especializados, podendo ser útil na assistência do AVC agudo. Os objetivos deste estudo foram avaliar a viabilidade de uma rede de telemedicina para o AVC no Sistema Único de Saúde na região de Ribeirão Preto e desenvolver um sistema de telemedicina para o AVC. Para a análise da viabilidade, foram realizados o levantamento de indicadores demográficos e epidemiológicos da população de municípios que constituem o Departamento Regional de Saúde de Ribeirão Preto (DRS XIII) e uma análise técnica e econômica relacionada à estrutura necessária. O sistema de registro eletrônico e videoconferência foi desenvolvido por equipe multiprofissional, baseado em diretrizes nacionais para sistemas de informação em saúde e protocolos padronizados para o atendimento do AVC agudo. Concluiu-se que uma rede de telemedicina entre o Hospital das Clínicas de Ribeirão Preto e os outros hospitais que possuem os pré-requisitos para cadastramento como Unidade de AVC no DRS XIII será estratégica para a expansão do atendimento qualificado do AVC na região, e sua viabilidade depende do cadastro destes serviços junto ao Ministério da Saúde, financiamento dos equipamentos e treinamento das equipes assistenciais. O sistema de telemedicina desenvolvido possibilitará o registro seguro dos atendimentos, a educação permanente das equipes e base de dados para pesquisas clínicas, contribuindo para a concretização desta e de outras redes de telemedicina brasileiras. / Stroke is a prevalent and disabling disease, whith insufficient treatment in Brazil, where is concentrated in a few high complexity centers. Telemedicine enables health care through communication technology between two or more professionals, or between the professionals and patients, in different locations, allowing increased access to specialized treatments, therefore useful in acute stroke treatment. This study objectives were to evaluate the feasibility of a public stroke telemedicine network at Ribeirão Preto region and to develop a stroke telemedicine eletronic system. For feasibility study, populational demographic and epidemiological indicators were compiled for the cities that constitute the Regional Health Department of Ribeirão Preto (DRS XIII) and a technical and economic analysis related to the necessary structure was performed. The electronical record and videoconference system was developed by a multiprofessional team, based on national guidelines for health information systems and standardized protocols for acute stroke care. A telemedicine network between the Hospital das Clínicas of Ribeirão Preto and the other hospitals that meet criteria for enrollment as Stroke Units in DRS XIII will be strategic for the expansion of regional qualified stroke care. Its viability depends on the registration of these services at the Health Ministry, equipment financing and assistance teams training. The developed telestroke system will enable the secure record of calls, the permanent education of the teams and a database for clinical research, contributing to the realization of this and other telemedicine networks.

De nos jours, les vidéos et les images sont devenues un moyen de communication très important. L'acquisition, la transmission, l'archivage et la visualisation de ces données visuelles, que ce soit à titre professionnel ou privé, augmentent de manière exponentielle. En conséquence, la confidentialité de ces contenus est devenue un problème majeur. Pour répondre à ce problème, le chiffrement sélectif est une solution qui assure la confidentialité visuelle des données en ne chiffrant qu'une partie des données. Le chiffrement sélectif permet de conserver le débit initial et de rester conforme aux standards vidéo. Ces travaux de thèse proposent plusieurs méthodes de chiffrement sélectif pour le standard vidéo H.264/AVC. Des méthodes de réduction du chiffrement sélectif grâce à l'architecture du standard H.264/AVC sont étudiées afin de trouver le ratio de chiffrement minimum mais suffisant pour assurer la confidentialité visuelle des données. Les mesures de qualité objectives sont utilisées pour évaluer la confidentialité visuelle des vidéos chiffrées. De plus, une nouvelle mesure de qualité est proposée pour analyser le scintillement des vidéos au cours du temps. Enfin, une méthode de chiffrement sélectif réduit régulé par des mesures de qualité est étudiée afin d'adapter le chiffrement en fonction de la confidentialité visuelle fixée. / Nowadays, videos and images are major sources of communication for professional or personal purposes. Their number grow exponentially and the confidentiality of the content has become a major problem for their acquisition, transmission, storage, and display. In order to solve this problem, selective encryption is a solution which provides visual privacy by encrypting only a part of the data. Selective encryption preserves the initial bit-rate and maintains compliance with the syntax of the standard video. This Ph.D thesis offers several methods of selective encryption for H.264/AVC video standard. Reduced selective encryption methods, based on the H.264/AVC architecture, are studied in order to find the minimum ratio of encryption but sufficient to ensure visual privacy. Objective quality measures are used to assess the visual privacy of encrypted videos. In addition, a new quality measure is proposed to analyze the video flicker over time. Finally, a method for a reduced selective encryption regulated by quality measures is studied to adapt the encryption depending on the visual privacy fixed.

L’objectif de ce travail a été de tester l’hypothèse selon laquelle l’effet bénéfique de l’administration de la forme recombinante de l’activateur tissulaire du plasminogène (rt-PA) chez le patient victime d’un accident vasculaire cérébral (AVC) ischémique ne résulte pas uniquement de son action fibrinolytique mais aussi de sa capacité à augmenter le brain-derived neurotrophic factor (BDNF) dans le cerveau. Dans ce but, nous avons conduit une première étude visant à évaluer chez l’animal sain, l’effet du rt-PA sur les taux cérébraux de BDNF. Dans une seconde approche, nous avons étudié l’effet du rt-PA sur les taux sériques de BDNF chez le patient victime d’un AVC ischémique et chez l’animal soumis à une ischémie cérébrale focale. Le sang a été prélevé chez l’Homme à l’admission (J0), J1, J7 et J90 après l’AVC, et chez le Rat avant et après (1h, 4h et 24h) l’ischémie. Le BDNF a été mesuré dans le cerveau par technique de Western blot et dans le sang par technique ELISA. Dans les deux études le rt-PA (Actilyse®) a été administré sous forme d’un bolus suivi d’une perfusion d’une heure. La première étude montre que 1) le rt-PA augmente les taux de BDNF dans l’hippocampe, 2) le traitement par MK801 (un antagoniste des récepteurs NMDA) mais pas par l’acide tranexamique (un inhibiteur de la plasmine) annule l’effet du rt-PA sur les taux de BDNF. La deuxième étude met en évidence que 1) la récupération neurologique est meilleure chez les patients recevant le rt-PA, 2) le traitement par rt-PA augmente les taux sériques de BDNF à J1 et J7 chez l’Homme, mais ne modifie pas les taux sanguins de BDNF chez l’animal, 3) les taux de BDNF ne sont pas corrélés à la récupération neurologique mais sont inversement corrélés au score cardiovasculaire du patient. En conclusion, nos résultats suggèrent que le rt-PA peut exercer un effet protecteur extra-fibrinolytique en augmentant les taux de BDNFm par une potentialisation de l’activité glutamatergique. Même si le rt-PA induit une meilleure récupération neurologique et augmente les taux circulants de BDNF chez les patients victimes d’un AVC, l’absence de corrélation entre ces deux paramètres n’est pas en faveur de l’utilisation du BDNF circulant comme un marqueur prédictif de récupération neurologique, mais pourrait être un reflet de la capacité de l’endothélium à sécréter le BDNF. / Our objective was to test the hypothesis that the beneficial effect of the administration of the recombinant form of tissue plasminogen activator (rt-PA) in ischemic stroke patient not only results from its fibrinolytic activity but also from its ability to increase brain-derived neurotrophic factor (BDNF) in the brain. To this end, we conducted an initial study to evaluate the effect of rt-PA on brain BDNF levels in healthy animals. In a second study, we investigated the effect of rt-PA on serum BDNF levels in ischemic stroke patients and in animals subjected to permanent focal cerebral ischemia. Blood samples were obtained from patient on admission (D0), D1, D7 and D90 after stroke and in rats before and after (1h, 4h and 24h) ischemia. BDNF was measured in the brain by Western blot and in the blood by ELISA. In both studies, the rt-PA (Actilyse®) was administered as a bolus followed by an infusion of one hour. The first study evidences that 1) rt-PA increases the BDNF levels in the hippocampus, 2) treatment with MK801 (a NMDA receptor antagonist) but not with tranexamic acid (a plasmin inhibitor) canceled the effect of rt-PA on BDNF levels. The second study exhibits that 1) neurological recovery was higher in the patients receiving rt-PA, 2) treatment with rt-PA increases serum BDNF at D1 and D7 in patients, but does not change the blood BDNF levels in animals, 3) BDNF levels are not correlated with neurological recovery but are inversely correlated to the patient cardiovascular score. In conclusion, our results suggest that rt-PA may have a protective extra-fibrinolytic effect by increasing in BDNF levels through a potentiation of glutamatergic pathway. Although rt-PA induces a better neurological recovery and increases circulating BDNF levels in stroke patients, the lack of correlation between these two parameters is not in favor of using circulating BDNF as a predictive marker of neurological recovery, but could be a reflect of the endothelium ability to synthesize BDNF.