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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.

INTRODUÇÃO: Alterações na postura ou no equilíbrio são ocorrências comuns em adultos com hemiparesia após um Acidente Vascular Encefálico (AVE). O objetivo desse trabalho foi estudar de forma comparativa o equilíbrio estático e parâmetros da marcha de pacientes hemiparéticos crônicos após AVE em hemisfério cerebral dominante (esquerdo) e não dominante (direito) e analisar as correlações da oscilação do centro de pressão (COP) com os parâmetros da marcha e com o nível de independência funcional (MIF). MÉTODOS: Foi realizado um estudo transversal, os pacientes foram provenientes do ambulatório de hemiplegia do Instituto de Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (IMREA-HCFMUSP). A análise da oscilação do COP foi realizada com uma plataforma de força, com olhos abertos e fechados. As variáveis mensuradas foram: área (amplitude de oscilação ântero-posterior e médio-lateral) e velocidade média de oscilação. Na marcha foram avaliados tamanhos do passo e passada, tempo de apoio e balanço, início duplo apoio, velocidade e cadência. RESULTADOS: Foram avaliados 21 pacientes hemiparéticos crônicos após AVE, nove com hemiparesia à direita e 12 à esquerda com predomínio braquial e mais de um ano de lesão. A avaliação da velocidade média de oscilação do COP, em ambos os grupos, apresentou maior desequilíbrio com os olhos fechados, porém não houve diferença estatística na avaliação entre os grupos de pacientes. O grupo com hemiparesia à esquerda apresentou melhores correlações do COP com os parâmetros da marcha. Dos parâmetros de equilíbrio avaliados, a área de oscilação do COP correlacionouse melhor com o tamanho da passada e com a MIF motora em ambos os grupos de pacientes. CONCLUSÃO: A área de oscilação do COP estático parece ser um bom indicador de equilíbrio, tamanho da passada e MIF motora em pacientes hemiparéticos após AVE. Não houve diferença no desempenho do equilíbrio estático entre os grupos de pacientes hemiparéticos crônicos quando comparado lesão em hemisfério dominante e não dominante. / INTRODUCTION: Posture or balance deficits are common findings in adults with hemiparesis after stroke. The aim of this study was analysis in the comparative way the gait parameters and balance in hemiparetic stroke patients in dominant (left) and non dominant (right) cerebral hemispheres, also the correlation the center of pressure (COP) with gait parameters and function independence measure (FIM). METHODS: A cross-sectional study was performed with outpatient hemiplegia group of Physical Medicine and Rehabilitation Institute of the University of São Paulo Faculty of Medicine Clinics Hospital (IMREA HCFMUSP). The measures analyzed were: area (anteroposterior and medio-lateral sway) and average velocity it was performed with a force platform with open and closed eyes. The gait parameters measured were step and stride length, stance and swing time, double support, speed and cadence. RESULTS: 21 patients were investigated, nine chronic patients with a right hemiparesis and 12 with a left, with brachial predominance and time since stroke at least 12 months. The outcomes sway velocity COP showed in both groups worst with eyes closed, however between the groups of chronic patients there was no statistical difference. The correlation results of COP and gait in left hemiparetic patients group were better. The COP sway area showed a better correlation with step and stride length and motor FIM in both groups of patients. CONCLUSION: The area of static COP appears to be a good indicator of balance, stride length and motor FIM in hemiparetic stroke patients. There was no difference in the performance of static balance in chronic hemiparetic stroke patients when compared dominant and non dominant hemispheres.

INTRODUÇÃO: O comprometimento da qualidade de vida após o acidente vascular cerebral tem sido associado com a sintomatologia depressiva. Entretanto, até o momento não se tem estudos investigando se a associação da sintomatologia depressiva com a qualidade de vida é independente da qualidade de vida no momento basal. Este estudo teve como objetivo principal investigar a associação entre sintomas depressivos detectados um mês após o acidente vascular cerebral e a qualidade de vida três meses posteriores ao acidente vascular cerebral e avaliar se essa associação independe da qualidade vida um mês após o acidente vascular cerebral. Como objetivo secundário visou investigar a associação entre sintomas depressivos detectados três meses após o acidente vascular cerebral e a qualidade de vida três meses após o acidente vascular cerebral e avaliar se essa associação independe da qualidade vida um mês após o acidente vascular cerebral. MÉTODOS: Neste estudo foram triados de modo consecutivo 343 pacientes admitidos na enfermaria de Neurologia do Hospital das Clínicas de São Paulo. Destes, foram elegíveis 106 pacientes, e 67 foram avaliados prospectivamente um e três meses após o acidente vascular cerebral. A avaliação psiquiátrica consistiu na aplicação da entrevista clínica estruturada para diagnóstico pelo DSM-IV e na versão de 31 itens da escala de Hamilton para depressão (HAM-D-31); a avaliação da qualidade de vida foi realizada com a versão de 36 itens do inventario de qualidade de vida do Medical Outcomes Study (SF-36). As avaliações foram realizadas em 2 momentos, sendo a primeira em média 37 dias (dp + 6) após o acidente vascular cerebral e a segunda em média 91,6 dias (dp + 5,4) após o acidente vascular cerebral. RESULTADOS: Houve associação entre sintomas depressivos um mês após o acidente vascular cerebral com a qualidade de vida três meses após o acidente vascular cerebral, mas tal associação deixou de ser significativa quando se considera a qualidade de vida um mês após o acidente vascular cerebral. Os sintomas depressivos três meses após o acidente vascular cerebral se associaram com a qualidade de vida três meses após o acidente vascular cerebral, independente da qualidade de vida um mês após o acidente vascular cerebral. CONCLUSÕES: Os resultados salientam a associação da sintomatologia depressiva com a qualidade de vida, e evidenciam a relevância da avaliação da qualidade de vida basal quando se investiga prospectivamente o impacto da sintomatologia depressiva sobre a qualidade de vida em pacientes que sofreram um acidente vascular cerebral. Por outro lado, a associação da sintomatologia depressiva com a qualidade de vida no mesmo momento da avaliação independe da qualidade de vida prévia / BACKGROUND: The impairment of quality of life after stroke has been associated with depressive symptoms. However, to date there has been studies investigating the association of depressive symptoms with quality of life are independent of the quality of life at baseline. This study aimed to investigate the association between depressive symptoms detected one month after the stroke and the quality of life three months after the stroke and assess whether this association is independent of the quality of life one month after the stroke. As a secondary objective was to investigate the association between depressive symptoms detected three months after the stroke and the quality of life three months after the stroke and assess whether this association is independent of the quality of life one month after the stroke. METHODS: This study screened 343 patients consecutively admitted to the neurology ward of the Hospital das Clinicas in Sao Paulo. Of these, 106 patients were eligible and 67 were prospectively evaluated one and three months after the stroke. The psychiatric evaluation was the application of structured clinical interview for DSM-IV diagnosis and 31 items on the version of the Hamilton Scale for Depression (HAM-D-31), the quality of life assessment was performed with the version of 36 items inventory of the quality of life of the Medical Outcomes Study (SF-36). The evaluations were carried out in two moments: the first 37 days on average (SD + 6) after the stroke and the second on average 91.6 days (SD + 5.4) after stroke. RESULTS: There was an association between depressive symptoms one month after the stroke with the quality of life three months after the stroke, but this association was no longer significant when considering the quality of life one month after the stroke. Depressive symptoms three months after stroke were associated with quality of life three months after stroke, regardless of the quality of life one month after the stroke. CONCLUSIONS: The results highlight the association of depressive symptoms with quality of life, and show the relevance of assessing the quality of life baseline when investigating prospectively the impact of depressive symptoms on quality of life in patients who suffered a stroke. Moreover, the association of depressive symptoms with the quality of life at the same time independent evaluation of the previous quality of life

Várias são as propostas para reabilitação da disfagia orofaríngea, sendo a eletroestimulação neuromuscular (EENM) uma nova modalidade de tratamento. Poucos são os trabalhos que comprovam a eficácia deste tratamento na reabilitação da disfagia e ainda não foram encontrados estudos que verificaram o efeito da EENM em idosos em fase tardia do acometimento vascular encefálico. Assim, o objetivo do presente trabalho foi verificar o efeito, a curto e médio prazo, da terapia da deglutição com EENM sensorial em idosos com sequelas de acidente vascular encefálico (AVE) que foram submetidos à terapia fonoaudiológica convencional sem sucesso, quanto ao nível de ingestão oral, ao quadro de disfagia orofaríngea e à qualidade de vida relacionada à deglutição. Para isto 10 indivíduos idosos, pósacidente vascular encefálico (AVE), que já haviam realizado terapia fonoaudiológica convencional foram classificados quanto ao nível de ingestão oral na escala funcional de ingestão oral (FOIS), submetidos à avaliação instrumental (videofluoroscopia) da deglutição utilizando-se líquido, alimento na consistência de pudim e sólido, a partir da qual foi analisado o grau da disfagia orofaríngea por meio da escala Dysphagia Outcome and Severity Scale (DOSS), realizada a classificação na escala de penetração e aspiração e na escala de resíduos. Também foi realizada a aplicação do protocolo de qualidade de vida relacionado à deglutição SWAL-QOL e aos procedimentos terapêuticos propostos, sendo que os exames foram repetidos imediatamente e três meses após a reabilitação. As sessões de terapia foram realizadas três vezes por semana e distribuídas em quatro semanas, totalizando 12 sessões. Cada sessão consistiu em duas etapas de 10 minutos de exercício, nas quais os pacientes foram solicitados a deglutirem a saliva com esforço, ou umapequena quantidade de água a cada 10 segundos durante a EENM. imediatamente após e três meses após as 12 sessões de terapia, todos os indivíduos foram submetidos novamente às avaliações iniciais. Os resultados demonstram que houve melhora da classificação da deglutição para 4 dos 10 pacientes imediatamente após a intervenção e, após três meses, um paciente ainda melhorou em mais um nível. Na análise estatística foi confirmada diferença significante na classificação da escala DOSS (0,023) entre os períodos. Além disso, houve diferença estatisticamente significante na somatória dos pontos do questionário de qualidade de vida relacionado à deglutição (p=0,008) entre os períodos pré e pós 3 meses de terapia com EENM. Não foram encontradas diferenças entre os períodos da reabilitação quanto ao nível de ingestão oral, classificação da penetração e aspiração, aos resíduos na faringe e aos tempos de trânsito oral e faríngeo (p>0,005). Portanto, a aplicação da eletroestimulação neuromuscular em nível sensorial em idosos acometidos por AVE resultou em diminuição do grau da disfagia em curto e médio prazo, além de melhora na qualidade de vida relacionada à deglutição após três meses de terapia. / There are several proposals for rehabilitation of oropharyngeal dysphagia, and the neuromuscular electrical stimulation (NMES) is a new type of treatment. There are few studies proving the efficiency of this treatment in oropharyngeal dysphagia, and studies verifying the effect of NMES in the elderly in late stage of cerebrovascular impairment haven´t been found yet. Thus, the objective of this study is to verify the short- and medium-term effect of the deglutition therapy with sensorial NMES in elderly patients with stroke sequelae, who underwent conventional speech therapy with no success, regarding the level of oral intake, the oropharyngeal dysphagia condition and the quality of life related to deglutition. In order to achieve such objective, 10 poststroke elderly patients, who had already undergone conventional speech therapy, were classified regarding the level of oral intake according to the functional oral intake scale (FOIS). They underwent swallowing instrumental assessment (fluoroscopy) with liquid, solid food and food in the consistency of pudding, their level of oropharyngeal dysphagia was analyzed by means of the Dysphagia Outcome and Severity Scale (DOSS), and they were rated by means of the penetration and aspiration scale and the waste scale. The SWAL-QOL outcomes tool was also applied regarding the quality of life in deglutition and the therapeutic procedures proposed. The sessions were performed three times per week for 4 weeks, a total of 12 sessions. One session consisted of two 10 minutes exercises with a 2 minutes rest period provided between exercises. Patients were asked to forcefully swallow their saliva or a small amount of water every 10 seconds during stimulation. The exams were repeated immediately and three months after rehabilitation. The results show there was an improvement in the deglutition rating for 4 out of the 10 patients immediately after the intervention and, after three months, one patient improved in one more level. In the statistical analysis, a significant difference was confirmed in the rating of the scale DOSS (0.023) between the periods. Furthermore, there was a statistically significant difference in the sum of the scores of the quality of life questionnaire related to deglutition (p=0.008) between the periods before and after 3-month therapy with NMES. No differences were found between the rehabilitation periods regarding the level of oral intake, the penetration and aspiration rating, the waste in the pharynx and oral and pharyngeal transit times (p>0.005). Therefore, the application of neuromuscular electrical stimulation in sensory level in elderly patients who had stroke resulted in the lowering of the dysphagia level in short- and long- term, in addition to the improvement in the quality of life related to deglutition after three months of therapy.

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.

Stroke is a neurovascular disease that frequently results in decreased motor and cognitive functioning. Obesity is a major risk factor associated with ischemic stroke and is thought to worsen the functional deficits observed after stroke. Previous findings from our laboratory suggest that worse motor deficits in obese animals may be a result from an exacerbated neuroinflammatory response. Most animal studies demonstrate an association between obesity and worse cognitive functioning after stroke. However, the mechanisms are not well studied. This study examines the neuroinflammatory response, ischemic brain tissue damage, and cognitive functioning in diet-induced obese mouse models during the chronic phase after ischemic stroke, defined as weeks after stroke. Our study found an earlier onset of cognitive deficits in obese mice after stroke compared to normal weight mice. We found no differences in the degree of brain damage in obese animals and normal weight animals 11 weeks after stroke, but observed higher levels of microgliosis in obese animals compared to normal weight animals. Due to the limitations of our study, additional studies should be done to assess the severity of cognitive deficits in obese animals compared to normal weight animals in the chronic phase after stroke. Further studies also need to be done to confirm our findings regarding the microglial response and degree of ischemic brain damage during the chronic phase.

Stroke is a widespread condition, which often leaves survivors with lasting deficits in motor function, however, physical rehabilitation is the only treatment available after the acute period. A large body of preclinical literature suggests dopamine-augmenting drugs, could enhance motor recovery following stroke. Unfortunately, mixed clinical results have prevented the implementation of such treatments, possibly due to the wide variety of G protein-coupled receptors these drugs can activate. Using a mouse photothrombosis stroke model and a battery of motor and sensorimotor behavioural tests, the current study aims to demonstrate proof of principle for the use of D1-class dopamine receptor agonists to enhance poststroke motor recovery and to evaluate the role of aerobic exercise rehabilitation in an asynchronous study design. The effect of light-dark cycle on behavioural outcome (horizontal ladder test, adhesive removal test, cylinder test) and histological outcome (infarct size) in photothrombotic stroke was evaluated in order to optimize the stroke model, but no there was no evidence of differences between strokes occurring during the light or dark period of a mouse’s circadian rhythm. A bioactive, suboptimal dose of D1-agonist dihydrexidine, was determined by evaluating its effect on locomotor activity and its ability to increase expression of immediate early gene c-fos. Using the determined dose, studies evaluating the efficacy of 7-days and 2-days of dihydrexidine administration on poststroke motor recovery, were performed, indicating efficacy of a 7-days, but not of a 2-days, course of treatment. The 7-days dihydrexidine treatment resulted in accelerated recovery as compared to a control group receiving saline. This work demonstrates, for the first time, proof of principle for the use of specific activation of D1-class dopamine receptors to enhance motor recovery following stroke.

Stroke is one of the leading causes of human death in the United States. The debilitating effects of an ischemic stroke are due to the fact that mammalian neurons are highly susceptible to hypoxia and subsequent oxygen reperfusion. From studies in Drosophila melanogaster, cGMP-dependent Protein Kinase (PKG) enzyme is thought to affect anoxia tolerance by modifying the electrical current through potassium ion channels. In this research, two animal models were employed: Drosophila melanogaster and mammalian neurons exposed to stroke-like conditions. First, in vivo studies using Drosophila were performed to further our knowledge about the differences between the naturally occurring variants of the Drosophila foraging gene, which shows different protein levels of PKG. Mitochondrial density and metabolic activity between two fly genotypes exposed to anoxia and reoxygenation were compared. It was found that flies with less enzyme potentially showed mitochondrial biogenesis and higher metabolic rates upon reoxygenation. Next, in vivo studies where PKG enzyme was activated pharmacologically were performed; it was found that the activation of the cGMP/PKG pathway led to neuroprotection upon anoxia and reoxygenation. Furthermore, this model was translated into the in vitro model using Drosophila cells. Instead of anoxia and reoxygenation, hypoxia mimetics and hydrogen peroxide were used to induce cellular injury. After showing the cGMP/PKG pathway activation-induced cell protection, the potential downstream targets of the molecular signaling as well as underlying biochemical changes were assessed. It was found that mitochondrial potassium ion channels were involved in the protective signaling and the signaling modulated metabolic function. Furthermore, it was found that acidosis protected Drosophila cells from cell death, metabolic disruption, and oxidative stress. Finally, this research was translated to a mammalian in vitro model of neuronal damage upon stroke-like conditions; there, it was demonstrated that the cGMP/PKG pathway activation in rat primary cortical neurons and human cortical neurons was protective from low oxygen and acute oxidative stress. The results of this study lead to a better understanding of molecular mechanisms taking place during low oxygen and oxidative stresses. Consequently, this knowledge may be used to identify potential therapeutic targets and treatments that may prevent detrimental neurological effects of an ischemic stroke in humans. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Cerebral small vessel disease (SVD) is a distinct microvascular disorder that can lead to lacunar stroke, an important stroke subtype that accounts for a quarter of all ischaemic strokes. SVD is associated with imaging biomarkers such as white matter hyperintensities (WMH). The cause of SVD is largely unknown, although inflammation and blood-brain barrier failure via endothelial dysfunction have been implicated. Elevated plasma biomarkers of inflammation are associated with coronary heart disease and large vessel stroke but the role of inflammation in SVD is less well understood. Our hypothesis is that inflammation plays a role in SVD and we sought to examine this by reviewing the literature for evidence of this, and by conducting a brain imaging study of patients with a known inflammatory disease and reviewing the images for evidence of inflammation and SVD, and comparing findings with controls groups. Section A: This thesis begins with a systematic review and meta-analysis of 13 plasma biomarkers of four physiological processes (coagulation, fibrinolysis, endothelial dysfunction and inflammation) in lacunar stroke versus non-lacunar stroke (to control for having any stroke) and non-stroke (to compare to the general population). We sought to know if there were differences in these biomarkers between lacunar stroke and other stroke subtypes and non-stroke controls as a way of generating hypotheses for the disease mechanisms that might lead to lacunar stroke. Findings revealed differences in several biomarkers between lacunar stroke and healthy controls but only fibrinogen, D-dimer, von Willebrand factor and interleukin-6 were different (all significantly lower in lacunar stroke) between lacunar stroke and other stroke subtypes. There was heterogeneity between studies, including variations in the definition of lacunar stroke and most studies measured the biomarkers in the acute phase post stroke, which is potentially confounding. To further examine plasma biomarkers of inflammation and endothelial dysfunction in SVD, we used data from a prior study of mild stroke conducted at the Brain Research Imaging Centre, University of Edinburgh, UK. Lacunar stroke patients were compared to cortical stroke patients. The lacunar group had lower levels of tissue plasminogen activator independent of age, sex and vascular risk factors but we found no difference in the other plasma biomarkers. Section B: Non-resolving systemic inflammation is a feature of inflammatory autoimmune rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These patients are at increased risk of stroke but much knowledge relates to stroke in general; less is known about associations with stroke subtypes including SVD, or when in life stroke risk is greatest. Consequently, we sought to better understand the influence of inflammatory rheumatic diseases on stroke and SVD. The review and meta-analysis of cerebrovascular disease in rheumatic diseases showed an excess risk of stroke in RA, SLE, ankylosing spondylitis, gout and psoriasis over the general population. Meta-analyses of stroke subtypes (ischaemic and haemorrhagic) in RA and SLE showed an excess risk of stroke over the general population. Stroke risk across rheumatic diseases was highest in those aged < 50 years and reduced with ageing. We then requested data from NHS Lothian covering 15 years so that we could assess stroke, including stroke subtypes, among patients diagnosed with various arthropathies. We linked 6,613 rheumatology patients’ records with stroke admission records, grouped the various rheumatic diseases into the two main types of arthritis, inflammatory and non-inflammatory, and also compared the strokes in these rheumatology patients to general population data. There was no difference in stroke prevalence between inflammatory and degenerative (non-inflammatory) arthropathies, although the strokes occurred up to two decades earlier than in the general population. Section C: Lastly, we conducted MRI neuroimaging in patients with SLE and reviewed and meta-analysed diffusion tensor imaging (DTI) (an imaging technique used to assess sub-visible white matter microstructure damage) in SLE to place our findings into context. The research question here was to ascertain if patients with a known inflammatory disease had brain imaging evidence of SVD, and to compare findings to controls. We compared imaging markers of SVD and DTI between SLE patients and age-matched healthy controls and sought associations between the imaging biomarkers and plasma biomarkers of inflammation and endothelial dysfunction, measures of fatigue and cognition, and scores of rheumatic disease activity. Fifty-one patients were recruited. There was higher mean diffusivity in all white matter tracts versus controls indicating a diffuse increase in brain water mobility in SLE. Meta-analysis confirmed higher mean diffusivity in SLE patients versus controls. Fatigue in SLE was significantly higher than a normal reference range and was associated with depression, anxiety, higher body mass index, lower mean diffusivity and some blood markers of inflammation and endothelial dysfunction. The most fatigued were youngest which explained the association with lower mean diffusivity. Damage to the brain’s white matter microstructure may be accelerated in SLE as the age-related declines in the general population are normally seen much later in life. The aging pattern is consistent with inflammation-related microvascular-mediated brain damage where the inflammation is systemic in origin. Summary: This thesis has demonstrated an increase in SVD burden in the inflammatory rheumatic disease SLE and increased stroke risk at younger ages in other inflammatory rheumatic diseases. Thus, systemic inflammation as seen in inflammatory rheumatic diseases could have effects on the brain directly, including influencing stroke risk which is clinically noteworthy and would benefit from further testing in appropriately designed studies such as an inception cohort that follows inflammatory rheumatic patients from diagnosis, with regular brain imaging to track brain changes and correlates with inflammatory profiles and impact on cognition.