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

Student Number : 0414012 - MSc dissertation - School of Therapeutic Sciences - Faculty of Health Sciences / Aim: The aim of this study was to quantify the level of ability and in particular walking ability of a group of stroke survivors resident in Soweto, between 3-6 months post incident. Design: Descriptive study in which comfortable walking speed over ten metres is correlated with the distance covered in six minutes and two minutes. Subjects: Forty one subjects after stroke divided into two groups. Twenty six with a Barthel Index initial score of ≤60 and fifteen with a score >60. Main Outcome Measures: Walking speed and two and six minute distance were compared between groups. In addition actual distance walked in six minutes was compared with the distance predicted by the ten-metre walking speed test and the distance predicted by normative reference equations. Heart rate was measured during the six minute walking test. Functional ability was compared using the Barthel Index within ten days post stroke and three to six months. Results: Of those who survived 90% of subjects were able to walk independently after stroke. The mean walking speed of 0.55 m/s demonstrated a strong correlation with the distance walked in six minutes (R2=0.816). However it underestimated the distance walked in six minutes by 7.4%. There were no significant differences between groups for the walking tests. The two minute walking test distance accurately predicted the results of the six minute walking test distance (R2=0.97). The average distance walked in six minutes by subjects after stroke was 40% of the distance predicted for healthy adults. For the functional walk test 95.5% of subjects had a heart rate within normal recommended limits. The functional walk test together with a measure of exertion (heart rate) may indicate an individual's ability to sustain submaximal activity. Subjects had minimal rehabilitation training. Lower limb pain did not significantly lower the walking speed (p=0.18) or distance walked in six minutes (p=0.17). Mean Barthel Index score at three to six months was 85.78 indicative of independence with minimal assistance. Although the mortality rate for the Barthel Index group with a score less than 60 is 30.7%, the prognosis of survivors was not uniformly poor. Conclusion: This study demonstrates that though a high percentage of subjects recovered independent walking after stroke in the Soweto community with minimal rehabilitation, their walking speed and distance walked are indicative of limited walking capacity. Walking speed and the two minute walking test could be used to predict functional walk test performance. Pain in the paretic lower limb though commonly reported did not appear to affect walking speed or distance walked. The use of the Barthel Index to predict activities and/or survival merits further investigation.

Distúrbios neurológicos como o Acidente Vascular Encefálico (AVE) podem causar alterações nos mecanismos responsáveis pela voz e deglutição, levando a quadros de disfonia e disfagia neurogênica, sendo que a maioria dos estudos aborda tais aspectos separadamente. O objetivo do presente trabalho foi estudar as funções de deglutição e voz, bem como a relação entre ambas, em indivíduos com sequelas de AVE. Foram analisados, para este estudo retrospectivo, os prontuários e exames de 30 idosos com média de 72 anos de idade. Foram realizados: aplicação de questionários referentes a queixas de deglutição e voz; avaliação perceptivo-auditiva da voz por meio da escala GRBASI; videoendoscopia da deglutição para classificação do grau da disfagia, da penetração e aspiração, além da taxa de gravidade de secreção; videoendoscopia da fonação, para observação de aspectos morfológicos e funcionais. Para verificar as correlações entre variáveis quantitativas e/ou qualitativas ordinais foi utilizado o Coeficiente de Correlação Spearman. Para verificar associação entre variáveis qualitativas nominais foram utilizados o teste exato de Fischer e o teste de Mann-Whitney. Em todos os testes foi adotado nível de significância de 5%. Para verificar a concordância entre juízes foi utilizada a estatística Kappa. Observou-se que 46% dos indivíduos referiu queixa vocal e voz muito fraca, 43% apresentou sensação de catarro preso na garganta e tosse; 46% dos indivíduos referiu dificuldades para mastigar, 36% engasgo durante as refeições e 32% ingestão de líquidos para ajudar na deglutição e tosse após as refeições. Na escala GRBASI, a maioria dos indivíduos apresentou o grau geral de disfonia e a rugosidade moderados para conversa espontânea e grau geral de disfonia e instabilidade moderados para a vogal /a/ sustentada. Com relação aos aspectos morfológicos, foi possível observar assimetria laríngea (73%), arqueamento bilateral da porção membranosa da prega vocal (77%) e saliência bilateral do processo vocal (77%). Quanto aos aspectos funcionais, observou-se fenda (57%), constrição supraglótica anteroposterior (57%) e constrição mediana (80%). A maioria dos indivíduos (83%) apresentou classificação 6 na escala DOSS, nível 1 para a consistência líquida (57%) e nível 0 para pastosa (57%) e sólida (63%) na escala de Taxa de Gravidade de Secreção. Foram encontradas relações entre sintomas de cansaço depois de falar muito com dificuldade para deglutir os alimentos (p=0,03), engasgo durante as refeições (p=0,00) e tosse após as refeições (p=0,01). Observou-se também relação entre catarro preso na garganta e engasgo durante as refeições (p=0,04), entre pigarro na garganta e ingestão de líquido para ajudar na deglutição (p=0,03), e entre pigarro na garganta e pigarro após as refeições (p=0,00). Ainda, foi observado que houve correlação entre estase em valécula para a consistência sólida e as características vocais de soprosidade (p=0,01) e astenia (p=0,02); relação entre a gravidade dos sinais de alteração da deglutição com a configuração laríngea. Concluiu-se que as características de voz e deglutição apresentadas pela população estudada foram semelhantes às frequentemente encontradas em idosos e que houve relações entre as funções de deglutição e voz. / Neurological disorders such as cerebrovascular accident (AVE) may cause changes in the mechanisms responsible for voice and swallowing, leading to dysphonia and neurogenic dysphagia and most studies addresses these aspects separately. The aim of this retrospective work was to study the functions of swallowing and voice as well as the relationship between them to individuals affected by sequel of stroke. We analyzed the medical charts of 30 patients averaging 72 years of age. Were performed: questionnaires regarding complaints of swallowing and voice; perceptual evaluation of voice through GRBASI scale; videoendoscopy of swallowing to classify the degree of dysphagia, penetration and aspiration, besides the severity rate of secretion; videoendoscopy of phonation, for observation of morphological and functional aspects. To verify the correlation between quantitative variables and / or qualitative ordinal was used Spearman Correlation Coefficient. To assess the association between nominal qualitative variables we used the Fisher exact test and Mann - Whitney. In all tests the level of significance was 5%. To verify the agreement between judges Kappa statistics was used. It was observed that 46% of the individuals reported voice complaints and very weak voice, 43% had feeling of phlegm stuck in throat and cough, 46% of subjects reported difficulty in chewing, 36% choking during meals and 32% drinking to assist in swallowing and coughing after meals. In GRBASI scale, most individuals showed grade and roughness moderate for spontaneous conversation and the grade and instability moderate for the vowel / a / sustained. With respect to morphology, was observed laryngeal asymmetry (73%), bilateral bowing of the membranous portion of the vocal fold (77%) and bilateral protrusion of the vocal process (77%). Regarding to the functional aspects, it was observed slit (57%), supraglottic anteroposterior constriction (57%) and median constriction (80%). Most individuals (83%) had rating 6 in DOSS scale, level 1 for liquid (57%) and level 0 to paste (57%) and solid (63%) in The Secretion Severity Rating scale. Relationships were found between symptoms of fatigue after speaking with much difficulty swallowing foods (p=0.03), choking during meals (p=0.00) and cough after meals (p=0.01). It was also observed relationship between phlegm stuck in my throat and choking during meals (p=0.04) between phlegm in the throat and fluid intake to aid in swallowing (p=0.03), and between phlegm in throat and hoarseness after meals (p=0.00). Still, it was observed that there was a correlation between stasis in the vallecula to solid and the vocal characteristics of breathiness (p=0.01), and asthenia (p=0.02), the relationship between the severity of the signs of swallowing disorders with laryngeal configuration. It was concluded that the characteristics of voice and swallowing presented by this study were similar to those often found in the elderly and that there were relations between the functions of swallowing and voice.

A espasticidade é uma das alterações decorrentes do Acidente Vascular Encefálico (AVE) que causa limitação no tônus muscular podendo gerar graves comprometimentos funcionais nos membros superiores. Pela característica do tecido neurológico lesado, frequentemente ocorre a cronificação das sequelas e incapacidades e atuar na minimização desses comprometimentos é objetivo dos profissionais da saúde. No entanto, há dificuldades na escolha da intervenção, análise de sua eficácia e aprimoramento dos estudos na área da reabilitação decorrentes da limitação nas estratégias de avaliação, sendo que nessa área as escalas são utilizadas com frequência. Dessa forma, esse estudo buscou desenvolver e validar a utilização clínica de um instrumento de medida da resistência isométrica ao estiramento passivo do grupo muscular flexor do punho em adultos e idosos com espasticidade decorrente do AVE. Foi desenvolvido um instrumento portátil capaz de medir a resistência da musculatura com um torquímetro. Foram realizados testes para analisar a validade, confiabilidade, sensibilidade e praticabilidade. Os testes foram feitos com os sujeitos sentados e com o antebraço e mão fixados no aparelho em seis diferentes posições do arco do movimento do punho, sendo que a articulação permaneceu estável por 20 segundos em cada posição. Foi realizada a avaliação de 108 sujeitos. A avaliação unilateral foi realizada em 21 sujeitos sem lesão neurológica e 27 sujeitos com AVE. A avaliação bilateral por dois examinadores foi realizada em 60 sujeitos, sendo 19 sem lesão e 41 com lesão neurológica. O instrumento mostrou-se capaz de mensurar as diferenças da resistência da musculatura em cinco das seis posições sendo relevante salientar que o instrumento foi sensível para apresentar a diferença entre população normal e com lesão e posteriormente apresentando a diferença entre lado comprometido e não comprometido. Os testes inter-examinadores mostraram boa correlação, no entanto, considerou-se a distribuição da segunda avaliação mais uniforme, sugerindo que se deve padronizar o uso para que o examinador realize a sequência de avaliação do arco do movimento por, no mínimo, duas vezes. Evidenciou-se ainda que o instrumento foi sensível para graduar a intensidade da sequela utilizando-se da comparação entre o lado não comprometido e o comprometido, sempre que a sequela seja apenas do hemicorpo visto que a graduação atribuída pela Escala Modificada de Ashworth possibilitou identificar correlação com as resistências apenas na avaliação grau 3, sendo que nos demais graus, não houve evidência estatística, corroborando com os também apresentados na literatura. Sugere-se, como continuidade do estudo, correlacionar os dados obtidos da avaliação da resistência estática à dinâmica. Esse instrumento desenvolvido pode ser utilizado para avaliação dos efeitos de órteses posicionadoras de punho, contribuindo assim, para o aprimoramento das estratégias de reabilitação. / Spasticity is one of the changes resulting from stroke which causes limitation in muscle tone and may cause severe functional impairment of the upper limbs. For the feature damaged neurological tissue often occurs chronicity of disabilities and act on these commitments is minimization objective of health professionals. However, there are difficulties in the choice of intervention, analysis and improvement of its effectiveness studies in rehabilitation due to limitations in assessment strategies, and this area scales are frequently used. Thus, this study sought to develop and validate the clinical use of an instrument for measuring isometric resistance to passive stretching of the wrist flexor muscle group in adult and elderly patients with spasticity due to stroke. We developed a portable instrument capable of measuring the muscular strength of a torquemeter. Tests were conducted to examine the validity, reliability, sensitivity and practicability. Tests were performed with the subjects seated with the forearm and hand set in the apparatus in six different positions of the arc of movement of the wrist, and the joint remained stable for 20 seconds at each position. Our evaluation of 108 subjects. The evaluation was performed unilaterally in 21 subjects without neurological injury and 27 subjects with stroke. A bilateral assessment by two examiners was performed in 60 subjects, 19 with and 41 without injury neurological injury. The instrument was able to measure differences in muscle strength in five of the six positions is important to note that the instrument was sensitive to show the difference between normal population and with injury and presents the difference between the affected and non-affected. The tests showed good inter-rater correlation, however, was considered a distribution more uniform the second evaluation, suggesting that it should use to standardize the examiner performs the evaluation sequence of the arc of movement by at least twice . It is further demonstrated that the instrument was sensitive to grade the intensity of the sequel using comparing the committed and uncommitted side where the sequel of the hemisphere is only seen that the graduation given by the Modified Ashworth Scale possible to identify a correlation with resistance only in the evaluation grade 3, and in the remaining degrees, there was no statistical evidence, corroborating also presented in the literature. It is suggested, as a continuation of the study, correlate data obtained from the evaluation of the resistance to static dynamic. This tool developed can be used to assess the effects of splint of wrist, thus contributing to the improvement of rehabilitation strategies.

O maior receio dos profissionais que atendem pacientes com queixa de disfagia é a dificuldade em diagnosticá-la, durante a avaliação clínica, principalmente quando os mesmos não apresentam sinais clínicos sugestivos de penetração e/ou aspiração laringotraqueal. Portanto, o objetivo deste estudo foi comparar a avaliação clínica da deglutição ao resultado da videofluoroscopia e à filmagem da videofluoroscopia, buscando identificar sinais comuns que sugiram e comprovem a aspiração silente. Foi realizado um estudo observacional e prospectivo com 49 pacientes adultos com diagnóstico de Acidente Vascular Cerebral. Uma anamnese foi realizada para coleta de informações. A avaliação clínica, incluiu a avaliação estrutural e funcional. Houve monitoração do paciente através da oximetria de pulso e a observação da ausculta cervical e sinais clínicos. Na videofluoroscopia, o paciente manteve-se monitorado pela oximetria e parâmetros clínicos foram analisados. Durante a videofluoroscopia o paciente foi filmado por uma câmera para posterior análise clínica. Em ambas as avaliações foi oferecido ao paciente a consistência líquida no volume de 100 ml no copo. As avaliações foram realizadas por profissionais distintas, ambas cegas uma na avaliação da outra. Dos pacientes avaliados 46 (94%) indivíduos apresentaram diagnóstico de Acidente Vascular Cerebral isquêmico. Do total, sete apresentaram aspiração, sendo que seis foram silente. A alteração da ausculta cervical na avaliação clínica e a presença de resíduo oral na filmagem se associaram a aspiração silente detectada na videofluoroscopia. Não foi observado relação entre alteração de saturação de oxigênio e aspiração silente. / The greatest fear of the professionals who attend patients with complaints of dysphagia is the difficulty in diagnosing it during the clinical evaluation, especially when they do not present clinical signs suggestive of laryngotracheal penetration and / or aspiration. Therefore, the objective of this study was to compare the clinical evaluation of swallowing to the videofluoroscopic result and videofluoroscopic filming, in order to identify common signs that suggest and prove the silent aspiration. An observational and prospective study was conducted with 49 adult patients with a diagnosis of stroke. An anamnesis was performed to collect information. Clinical evaluation included structural and functional assessment. There was patient monitoring through pulse oximetry and observation of cervical auscultation and clinical signs. In videofluoroscopic, the patient was monitored by oximetry and clinical parameters were analyzed. During the videofluoroscopic the patient was filmed by a camera for further clinical examination. In both evaluations was offered 100 ml of the liquid in the cup. The evaluations were performed by distinct professionals, both blinded one in the evaluation of the other. Of the patients evaluated, 46 (94%) individuals had a diagnosis of ischemic stroke. Of the total, seven had aspiration, six of which were silent. Alteration of the cervical auscultation in clinical evaluation and presence of oral residue in filming were associated with silent aspiration detected in videofluoroscopic. No relation between alteration of oxygen saturation and silent aspiration was observed.

Background: Stroke is the fifth leading cause of death in Tennessee. The Tennessee Stroke Registry (TSR) Act requires East Tennessee State University’s College of Public Health to maintain a stroke database of participating hospitals and produce an annual report. Currently, twelve hospitals submit data to the TSR. Objectives: The TSR seeks to provide stroke information to Tennessee residents, policy makers, and health-care professionals. This presentation will highlight the key findings of the 2015 TSR report and will serve as an update to the 2014 report presented at the 2015 Tennessee Public Health Association conference. Methods: Data for the TSR was collected via Quintiles, American Heart Association’s online database. Microsoft Excel and ArcMap 10.3.x were used to conduct a descriptive analysis of stroke across Tennessee, observing characteristics of both stroke overall and of individual subtypes. Results: Seventy-nine percent of strokes in Tennessee in 2015 were ischemic. Some subtypes showed significantly different proportions of males versus females. For instance, females made up 63% of subarachnoid hemorrhage patients. The average age of stroke patients in Tennessee was 67.1 years, but varied for subtypes, ranging from 58.2 to 69 years. The majority of stroke patients (75.1%) had a recorded history of hypertension. Counties with high stroke mortality rates tended to cluster in areas of few certified stroke centers. Conclusion: Stroke subtypes exhibited different characteristics than stroke overall and geographic disparities were highlighted through the descriptive mapping. Identifying and understanding these differences and disparities can help in addressing ways to improve stroke care in Tennessee.

abstract: Stroke remains a leading cause of adult disability in the United States. In recent studies, chronic vagus nerve stimulation (VNS) has been proven to enhance functional recovery when paired with motor rehabilitation training after stroke. Other studies have also demonstrated that delivering VNS during the onset of a stroke may elicit some neuroprotective effects as observed in remaining neural tissue and motor function. While these studies have demonstrated the benefits of VNS as a treatment or therapy in combatting stroke damage, the mechanisms responsible for these effects are still not well understood or known. The aim of this research was to further investigate the mechanisms underlying the efficacy of acute VNS treatment of stroke by observing the effect of VNS when applied after the onset of stroke. Animals were randomly assigned to three groups: Stroke animals received cortical ischemia (ET-1 injection), VNS+Stroke animals received acute VNS starting within 48 hours after cortical ischemia and continuing once per day for three days, or Control animals which received neither the injury nor stimulation. Results showed that stroke animals receiving acute VNS had smaller lesion volumes and larger motor cortical maps than those in the Stroke group. The results suggest VNS may confer neuroprotective effects when delivered within the first 96 hours of stroke. / Dissertation/Thesis / Masters Thesis Electrical Engineering 2019

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. IL-1’s isoforms, IL-1α and IL-1β, were long thought to have similar function. While IL-1β has been extensively studied in stroke, the role of IL-1α during post stroke inflammation has been overlooked. Because IL-1 inhibitors have been unsuccessful in clinical application, we reasoned that IL-1α may provide previously unknown benefits to the brain after injury. We hypothesized that IL-1α could be protective or even accelerate reparative processes in the brain such as producing new blood vessels (angiogenesis) or neurons (neurogenesis). To test that IL-1α is protective after stroke, we tested IL-1α’s protective effects on primary cortical neurons in in vitro models of stroke. We showed that IL-1α was directly protective on primary cortical neurons in a dose-dependent fashion. We then performed mouse middle cerebral artery occlusion stroke studies to determine the safety of giving IL-1α in vivo. These studies showed that administering IL-1α acutely was neuroprotective. However, intravenous (IV) administration of IL-1α resulted in transient, hemodynamic changes following drug delivery. To minimize these systemic effects, we administered IL-1α intra-arterially (IA) directly into the stroke affected brain tissue, allowing us to significantly lower the concentration of administered IL-1α. In comparison to IV, IA IL-1α showed greater histological protection from ischemic injury as well as improved functional recovery following stroke, all without systemic side effects. To test that IL-1α could aid in neurorepair following stroke, we tested IL-1α’s ability to help damaged blood vessels repair in vitro. We found that IL-1α significantly increased brain endothelial cell activation, proliferation, migration, and capillary formation. We tested IL-1α’s proangiogenic properties in vivo by administering IL-1α three days following stroke. Delayed administration allowed us to separate IL-1α’s acute neuroprotective effects from potential subacute angiogenic effects. We found that mice receiving IL-1α performed significantly better on behavioral tests and also showed greater vascularization within the penumbra two weeks following stroke. We also found that IL-1α treated animals showed more endothelial activation than vehicle treated animals. Finally, our studies showed that IL-1α treated animals showed increased early-phase neurogenesis with evidence of increased proliferation at the subventricular zone suggesting that IL-1α’s beneficial effects are even more far-reaching than previously thought. In conclusion, our experiments suggest that the inflammatory cytokine IL-1α is neuroprotective and neuroreparative in experimental ischemic stroke and worthy of further study as a novel stroke therapy.

Stroke continues to plague the United States, affecting 795,000 people annually. Although stroke mortality has decreased, the overall incidence of stroke appears essentially unchanged. With a population that is projected to increase in age and stroke risk over the next 10-15 years, this is concerning. Current stroke prevention education may not be adequately tailored to community learning needs. Analyzing existing demographic data within electronic medical records may allow healthcare systems to identify high-risk neighborhoods by geocoding stroke diagnoses and then completing a qualitative analysis within the target community of specific stroke knowledge deficits. That information may then inform stroke prevention education for that neighborhood. A descriptive, exploratory approach was used to identify a community with a high incidence of stroke using geocoded demographic data from patients coding out with a stroke diagnosis. Qualitative interviews conducted within the community yielded the following themes: fragmented knowledge of stroke causes and risk factors, unawareness of hypertension and diabetes as significant risk factors for stroke, knowing but experiencing challenges to engaging in healthy practices—specifically, diet and exercise, and financial barriers to healthcare resources. While most of the participants had adequate healthcare coverage and reported regular interactions with a primary healthcare provider, this community continued to experience a higher incidence of stroke than surrounding neighborhoods. The findings of this study highlighted specific challenges to stroke prevention that may inform future stroke prevention initiatives. Future research in other communities using this approach may provide additional insights into the specific knowledge deficits unique to communities, as well as revealing patterns and trends in stroke prevention knowledge. Approaching stroke prevention education using only data obtained from large registries may provide a broad overview of knowledge deficits, but lack the specificity necessary to effectively address stroke knowledge needs at the community level. Recognizing the challenges inherent with behavior modification for implementing lifestyle changes should also be considered when designing future stroke education. Harnessing technology in the form of web applications, text messaging, and email for maintaining communication with patients may improve effectiveness of stroke prevention interventions. Implementing a comprehensive health promotion program that addresses specific community needs with tailored health education and behavioral support may lead to decreased incidence of cerebrovascular disease in this community and provide a model for managing other preventable diseases. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

archives@tulane.edu / Experimental stroke in endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) knockout mice showed diverse effects on brain injury. nNOS and eNOS have been shown to uncouple in pathological conditions to produce superoxide. Oxidative stress is believed to be the underlying cause of several cardiovascular diseases including ischemic stroke. However, the role of eNOS and nNOS uncoupling in ischemic stroke is not well studied. Our objective of the study was to determine the effect of eNOS and nNOS inhibition on reactive oxygen species (ROS), NO, viability and mitochondrial bioenergetics in rat brain microvascular endothelial cells (BMECs) and rat cortical neurons following oxygen-glucose deprivation-reoxygenation (OGD/R). We found that non-specific inhibition of NOS in endothelial cells reduced ROS levels in BMECs but increased ROS levels in neurons under normoxia. This suggests that a pool of uncoupled NOS exists in the BMECs whereas the dominant functional NOS in neurons produces NO. We observed increased levels of ROS following OGD/R that is sensitive to NOS inhibition in both BMECs and neurons indicating eNOS and nNOS uncoupling during OGD/R. Furthermore, NOS inhibition reduced mitochondrial respiration while it improved cell survival rate in both BMECs and neurons following OGD/R. Thus, it is possible that decreased mitochondrial respiration in the immediate aftermath (4 hours) of OGD/R could be protective against reoxygenation injury. Moreover, we identified the expression of nNOS in BMECs from rat, human, and mouse. We observed that the nNOS in the BMECs constitutively produces superoxide under physiological conditions instead of NO. In contrast, nNOS in the neurons produces NO and doesn’t contribute to ROS. We also confirmed the nNOS expression and its function in freshly isolated rat brain microvessels. In addition, we developed a novel method to measure mitochondrial respiration in freshly isolated mouse brain microvessels using Seahorse XFe24 Analyzer. We validated the method by demonstrating impaired mitochondrial respiration in cerebral microvessels isolated from old mice compared to young mice. In summary, the present doctoral research investigated the distinct role of NOS isoforms in BMECs and Neurons leading to the identification of novel functional variant of nNOS in BMECs and brain microvessels. / 1 / RAMARAO SVNL