The leading cause of death in patients who survive subarachnoid hemorrhage (SAH) is stroke as a result of cerebral arterial vasospasm1. Such vasospasms involve a vasoactive response, but they remain enigmatic and no clinical treatment has proven effective in prevention or reduction2. Arteries remodel in response to diverse mechanical loads and chemical factors. Following SAH, the surrounding vasculature is exposed to a radically altered chemo-mechanical environment. It is our hypothesis that chemical stimuli associated with the formation of an extravascular blood clot dominates the maladaptive growth and remodeling response early on, thus leading to important structural changes. However, it is not clear which of the many chemical factors are key players in the production of vasospasm. Before an accurate picture of the etiology of vasospasm can be produced, it is imperative to gain a better understanding of the non-pathogenic cerebral vasculature. In particular, the rabbit basilar artery is a well established model for vasospasm. However, surprisingly little is known about the mechanical properties of the rabbit basilar artery. Using an in vitro custom organ culture and mechanical testing device, acute and cultured basilar arteries from male White New Zealand specific pathogen free rabbits underwent cyclic pressurization tests at in vivo conditions and controlled levels of myogenic tone. Sections of basilar arteries were imaged for collagen fiber orientation at 0, 40 and 80 mmHg at in vivo stretch conditions using nonlinear optical microscopy. The nonlinear stress-strain curves provide baseline characteristics for acute and short-term culture basilar arteries. The active and passive testing creates a framework for interpreting the basal tone of arteries in our culture system. Nonlinear optical microscopy second harmonic generation provides unique microstructural information and allows imaging of live, intact arteries while maintaining in vivo geometries and conditions. Collagen fibers were found to be widely distributed about the axial direction in the adventitial layer and narrowly distributed about the circumferential direction in the adventitial layer. The quantified collagen fiber angles within the artery wall further support the development of accurate mathematical models.

The leading cause of death in patients who survive subarachnoid hemorrhage (SAH) is stroke as a result of cerebral arterial vasospasm1. Such vasospasms involve a vasoactive response, but they remain enigmatic and no clinical treatment has proven effective in prevention or reduction2. Arteries remodel in response to diverse mechanical loads and chemical factors. Following SAH, the surrounding vasculature is exposed to a radically altered chemo-mechanical environment. It is our hypothesis that chemical stimuli associated with the formation of an extravascular blood clot dominates the maladaptive growth and remodeling response early on, thus leading to important structural changes. However, it is not clear which of the many chemical factors are key players in the production of vasospasm. Before an accurate picture of the etiology of vasospasm can be produced, it is imperative to gain a better understanding of the non-pathogenic cerebral vasculature. In particular, the rabbit basilar artery is a well established model for vasospasm. However, surprisingly little is known about the mechanical properties of the rabbit basilar artery. Using an in vitro custom organ culture and mechanical testing device, acute and cultured basilar arteries from male White New Zealand specific pathogen free rabbits underwent cyclic pressurization tests at in vivo conditions and controlled levels of myogenic tone. Sections of basilar arteries were imaged for collagen fiber orientation at 0, 40 and 80 mmHg at in vivo stretch conditions using nonlinear optical microscopy. The nonlinear stress-strain curves provide baseline characteristics for acute and short-term culture basilar arteries. The active and passive testing creates a framework for interpreting the basal tone of arteries in our culture system. Nonlinear optical microscopy second harmonic generation provides unique microstructural information and allows imaging of live, intact arteries while maintaining in vivo geometries and conditions. Collagen fibers were found to be widely distributed about the axial direction in the adventitial layer and narrowly distributed about the circumferential direction in the adventitial layer. The quantified collagen fiber angles within the artery wall further support the development of accurate mathematical models.

Intracellular membrane potential (Em) and force development were measured in rabbit basilar artery to help elucidate the mechanism of action of dopamine in this preparation. There was a strong correlation between membrane depolarization and contraction (r=0.95) between 3×10-7 M to 10-4 M dopamine. When the vascular muscle cells were depolarized by elevating [K]o there was a Em dependent decrease in force development in response to dopamine. Significant reduction of dopamine stimulated force development was observed when the vessel was depolarized by 5-6 mV by excess extracellular K+ and 90% inhibition was seen when the artery was depolarized to -20mv. When Ca++ influx was blocked, dopamine no longer induced force development. Such findings suggest that dopamine cotracts rabbit basilar artery by a mechanism involving membrane depolarization. This process may involve an influx of extracellular Ca++ through voltage sensitive channels.

No description available.

Esta pesquisa analisa experimentalmente as diferenças de comportamento entre a versão clássica e a modificada da craniotomia subtemporal quanto à retração do lobo temporal. A retração é medida pelo ângulo de visão, através do microscópio, obtido ao mirar-se estruturas previamente estabelecidas. Estudou-se a correlação estatística entre a retração cerebral e os diâmetros transversos do crânio, a profundidade da fossa temporal e a altura da bifurcação medida em relação à tenda do cerebelo e à clinóide posterior. É considerada a relação entre estes achados e os aspectos pertinentes à opção entre as craniotomias pterional e subtemporal para o tratamento cirúrgico dos aneurismas da porção superior da artéria basilar. / This paper is an experimental analysis between the classic and the modified subtemporal procedures, regarding the cerebral retraction required to approach the interpeduncular cistern and the basilar artery bifurcation. The retraction is assumed to be proportional to the angle of sight, through the microscope, required to observe the basilar bifurcation and other structures. The statistical correlations between the degree of brain retraction and the transverse diameters of the skull, the vertical length of the temporal fossa and the position of the basilar bifurcation in relation to the posterior clinoid and the tentorium are analysed. Considerations are made regarding these findings and the many aspects involved in the options between the pterional and the subtemporal approaches in the surgical treatment of the basilar bifurcation aneurysms

Esta pesquisa analisa experimentalmente as diferenças de comportamento entre a versão clássica e a modificada da craniotomia subtemporal quanto à retração do lobo temporal. A retração é medida pelo ângulo de visão, através do microscópio, obtido ao mirar-se estruturas previamente estabelecidas. Estudou-se a correlação estatística entre a retração cerebral e os diâmetros transversos do crânio, a profundidade da fossa temporal e a altura da bifurcação medida em relação à tenda do cerebelo e à clinóide posterior. É considerada a relação entre estes achados e os aspectos pertinentes à opção entre as craniotomias pterional e subtemporal para o tratamento cirúrgico dos aneurismas da porção superior da artéria basilar. / This paper is an experimental analysis between the classic and the modified subtemporal procedures, regarding the cerebral retraction required to approach the interpeduncular cistern and the basilar artery bifurcation. The retraction is assumed to be proportional to the angle of sight, through the microscope, required to observe the basilar bifurcation and other structures. The statistical correlations between the degree of brain retraction and the transverse diameters of the skull, the vertical length of the temporal fossa and the position of the basilar bifurcation in relation to the posterior clinoid and the tentorium are analysed. Considerations are made regarding these findings and the many aspects involved in the options between the pterional and the subtemporal approaches in the surgical treatment of the basilar bifurcation aneurysms

Hypertension is a risk factor for many cardiovascular and cerebrovascular diseases such as atherosclerosis and stroke. It is therefore important to understand the effect of hypertension on temporal growth and remodeling of arteries. In this study, experimental hypertension was induced in the mini-pig by aortic coarctation. Basilar arteries and aortas were collected for analysis over an eight week period of hypertension with specimens from normotensive animals serving as controls. Changes in mechanical properties of the basilar artery were evaluated by in vitro pressure-diameter tests on intact cylindrical segments at their in situ length. The basilar arteries from hypertensive animals became less distensible, reflecting increases in both structural and material stiffness, compared to their normotensive counterparts. The circumferential stress rapidly returned toward its homeostatic value by increasing the wall thickness within two weeks. Immunohistochemistry, which is capable of illustrating the localization and distribution of protein expression, was performed to examine changes in wall constituents in the aorta. The increased medial thickness observed in hypertensive pigs compared to normotensive pigs was due to hyperplasia of smooth muscle cells (SMCs) and accumulation of extracellular matrix proteins, which were accompanied by the phenotypic modulation of SMCs. The increased interlamellar thickness, collagen fibers, and the thickness of elastic lamina found in the inner media of hypertensive animal may be associated with the gradient of stress decreasing into the outer media. SMC proliferation, if any, was found evenly distributed across the media, however. In cases showing increased proliferation and matrix protein synthesis, the SMC contractile markers were down-regulated whereas the SMC synthetic markers were up-regulated. While the aortic intima appeared normal in the normotensive animals, neointima formation, which may predispose the vessel to atheroma formation, was found in the hypertensive animals. Immunohistochemistry of Hsp47 and procollagen revealed that the endothelial cells (ECs) may produce collagen, specifically type I collagen in response to hypertension and contribute to the thickened intima. In addition, lectin staining for ECs markers and immunostaining for eNOS suggested that endothelial cells may transdifferentiate into intimal SMCs. These findings suggested an alternative role that ECs may play in hypertension-induced atherogenesis.

Submitted by Edson Rodrigo Del Rio Vieira null (rodrigodelrio@uol.com.br) on 2016-12-04T15:37:23Z No. of bitstreams: 1 Vieira_ERDR_ME_ILHA.pdf: 8354186 bytes, checksum: 2d0cc3e0eee52b2d654d403b5f472d54 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-12-06T13:47:18Z (GMT) No. of bitstreams: 1 vieira_erdr_me_ilha.pdf: 8354186 bytes, checksum: 2d0cc3e0eee52b2d654d403b5f472d54 (MD5) / Made available in DSpace on 2016-12-06T13:47:18Z (GMT). No. of bitstreams: 1 vieira_erdr_me_ilha.pdf: 8354186 bytes, checksum: 2d0cc3e0eee52b2d654d403b5f472d54 (MD5) Previous issue date: 2016-08-26 / Item merged in doublecheck by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-01-20T16:08:54Z Item was identical to item(s): 145094, 144451 at handle(s): http://hdl.handle.net/11449/145008, http://hdl.handle.net/11449/144479 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Segundo a Sociedade de Cirurgia Vascular da América do Norte e Sociedade Internacional de Cirurgia Cardiovascular, aneurismas são dilatações superiores ou iguais a 1,5 vezes o diâmetro original da artéria. Estima-se que aproximadamente 2% a 5% da população adulta tem algum tipo de aneurisma cerebral. Grande parte dos casos não chegam a causar sintomas ou gerar problemas graves, entretanto o risco de sua ruptura gera consequências clínicas desafiadoras, visto que tem grande taxa de morbimortalidade, tornando difícil a tarefa de tomar a decisão de intervenção ou não no tratamento do aneurisma. Neste trabalho, propõe-se o estudo numérico do escoamento em aneurismas do tipo basilar empregando-se a técnica da dinâmica de fluidos computacional. Comparando diferentes casos de aneurismas rompidos e não rompidos, identificamos características no escoamento para auxiliar a tomada de decisões no tratamento de pacientes. Os casos de aneurismas são oriundos de tomografias computadorizadas de pacientes reais, os quais foram utilizados para a criação dos modelos digitais. As simulações computacionais foram realizadas com oprogramaopen sourceOpenFOAM® . Outros programasopen source também foram utilizados na criação dos modelos, assim como para o tratamento dos resultados. Identificamos uma correlação entre os dados de tensão cisalhante na parede e a probabilidade de ruptura. Para os oito casos estudados, os resultados de previsão de ruptura e não ruptura apresentaram grande compatibilidade. Dentre os quatrocasos de aneurismas previamente reconhecidos como rompidos, trêsforam identificados pelas simulações comoaneurismas com alto risco de ruptura e umfoi identificado com risco intermediário de ruptura. Já para os quatro casos de aneurismas previamente reconhecidos como rompidos, doisforam identificados pelas simulações como aneurismas de baixo risco de ruptura e doiscom risco intermediário de ruptura. / According to the Society for Vascular Surgery of North America and the International Society of Cardiovascular Surgery, aneurysms are dilations greater than or equal to 1.5 times the original artery diameter.It is estimated that approximately 2% to 5% of adult population has some type of brain aneurysm. In most cases aneurysms are small enough not to cause symptoms or serious problems, however the risk of rupture generates challenging clinical consequences, since they have high rate of morbidity and mortality, making difficult the decision whether or not to treat the aneurysm. This work presents the study of the flow through the basilar type aneurysms using the technique of computational fluid dynamics. Comparing different cases of ruptured and nonruptured aneurysms, we identified some flow characteristics that can help in the decision making process for the treatment of patients. The cases studied were taken from CT scans of real patients, which were used for creation of digital models of aneurysm used in the simulations. The simulations were performed using open source software OpenFOAM® . Others open source softwares were also used in the creation of models as well as for post processing. We investigated the correlation between wall shear stress and the likelihood of rupture. For the eight cases, the rupture prediction results showed good correlation. For the four ruptured cases simulated, three were identified with high risk of rupture and one with intermediary risk of rupture. As for the four not ruptured cases, two were identified with low risk of rupture and two with intermediary risk of rupture. / CNPq: 134375/2015-7

Orientador: José Luiz Gasche / Resumo: Segundo a Sociedade de Cirurgia Vascular da América do Norte e Sociedade Internacional de Cirurgia Cardiovascular, aneurismas são dilatações superiores ou iguais a 1,5 vezes o diâmetro original da artéria. Estima-se que aproximadamente 2% a 5% da população adulta tem algum tipo de aneurisma cerebral. Grande parte dos casos não chegam a causar sintomas ou gerar problemas graves, entretanto o risco de sua ruptura gera consequências clínicas desafiadoras, visto que tem grande taxa de morbimortalidade, tornando difícil a tarefa de tomar a decisão de intervenção ou não no tratamento do aneurisma. Neste trabalho, propõe-se o estudo numérico do escoamento em aneurismas do tipo basilar empregando-se a técnica da dinâmica de fluidos computacional. Comparando diferentes casos de aneurismas rompidos e não rompidos, identificamos características no escoamento para auxiliar a tomada de decisões no tratamento de pacientes. Os casos de aneurismas são oriundos de tomografias computadorizadas de pacientes reais, os quais foram utilizados para a criação dos modelos digitais. As simulações computacionais foram realizadas com o programa open source OpenFOAM®. Outros programas open source também foram utilizados na criação dos modelos, assim como para o tratamento dos resultados. Analisando os dados de máxima pressão e tensão cisalhante nas paredes na região do aneurisma apenas (domo e pescoço), propomos um critério para identificar os aneurismas rompidos e não rompidos. Considerando que os aneur... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

INTRODUÇÃO: Estudos de amostras de pacientes com lesões vasculares em território comum ao irrigado pela Artéria Basilar, mas não especificamente causados por sua oclusão, encontram como principais achados cognitivos os prejuízos de memória, percepção, atenção e função executiva. Entretanto, não há estudos, até o momento, que tenham investigado as alterações cognitivas decorrentes de oclusão da artéria basilar. O objetivo deste trabalho, portanto, foi: 1) caracterizar uma amostra de pacientes após o Acidente Vascular Encefálico isquêmico em território da artéria basilar; 2) delinear seu perfil cognitivo e funcional; 3) correlacionar os resultados dos testes cognitivos com variáveis demográficas, clínicas e radiológicas. MÉTODOS: Foram recrutados 28 pacientes adultos (0 a 25 anos de educação), com infarto em território de Artéria Basilar que não apresentavam outra patologia neurológica ou psiquiátrica. Paralelamente, foram recrutados 27 sujeitos saudáveis controlados em idade e escolaridade ao grupo de pacientes. Todos foram submetidos a uma abrangente avaliação neuropsicológica que incluiu testes para eficiência intelectual, memória de curto e longo prazo, linguagem, funções executivas, atenção, habilidades visuoperceptivas e espaciais, e escalas de funcionalidade e de humor. As informações clínicas e sociodemográficas foram obtidas junto aos familiares dos pacientes e nos prontuários médicos. Um experiente neurorradiologista analisou as imagens. Foram conduzidas análises estatísticas descritivas, correlações de Spearman ou Pearson, comparações entre grupo com Mann-Whitney ou T-Student, análises de covariância (ANCOVA) e de regressão linear multivariada. RESULTADOS: A média de fator de risco para os pacientes foi de 4,64 (1,52). As lesões acometeram, principalmente, o cerebelo (71%) e o tronco encefálico (68%), e 70% dos pacientes apresentaram alterações de substância branca dentro do esperado para a idade. Na comparação entre pacientes e controles, verificou-se diferença significativa em Memória de Longo Prazo (p <= 0,001), Funções Executivas (p = 0,003), Percepção (p = 0,001), Velocidade de Processamento (p <= 0,001) e Atenção (p <= 0,001), com resultados piores para o grupo de pacientes. Esta diferença significativa não se manteve após análise de covariância utilizando como variável controle a velocidade de processamento de informações. Cinco (18%) dos pacientes apresentaram dependência funcional segundo as escalas de funcionalidade. Lesão em tálamo estava associada a déficits de Memória de Longo Prazo (p= 0,004), Funções Executivas (p = 0,030), Percepção (p = 0,007) e Atenção (p = 0,026). O humor, o tempo de doença, a quantidade de fatores de risco, a extensão da estenose, a presença de lesões de substância branca ou de múltiplos Acidentes Vasculares Encefálicos não impactaram na cognição. CONCLUSÕES: As características demográficas, clínicas e radiológicas da amostra estudada foram semelhantes às descritas na literatura. O perfil cognitivo após isquemia de artéria basilar foi caracterizado por prejuízos de velocidade de processamento de informações, memória de longo prazo, atenção, função executiva e percepção. Apesar do referido prognóstico desfavorável, os pacientes com história de oclusão da artéria basilar apresentaram longa sobrevida e funcionalidade atual satisfatória. Foi evidente apenas a relação entre a presença de lesão em tálamo e déficits de percepção, atenção, memória de longo prazo e funções executivas / INTRODUCTION: Cognitive impairments of memory, perception, attention, and executive function are the main problems found in patient samples with vascular lesions in similar regions to those irrigated by the basilar artery, but not specifically caused by its occlusion. However, no studies have yet investigated the cognitive changes caused by basilar artery occlusion.The aims of this study, therefore, were: 1) to characterize a sample of patients after ischemic cerebrovascular accident in the basilar artery territory; 2) to outline their cognitive and functional profiles; and 3) to correlate the results of cognitive tests with demographic, clinical, and radiological variables. METHODS: Altogether, 28 adult patients (with 0-25 years of education), who had an infarction in the basilar artery territory but no other neurological or psychiatric disorders, were recruited for this study. In parallel, 27 healthy subjects who were matched in age and education to the patients were also recruited as controls. All patients underwent a comprehensive neuropsychological assessment that included tests for intellectual efficiency, short- and long-term memory, language, executive function, attention, visual perception and spatial skills, and functionality scales and mood. Clinical and sociodemographic information was obtained from the patients\' relatives and medical records. An experienced neuroradiologist reviewed the images. Descriptive statistical analyses, Spearman or Pearson correlations, comparisons between groups with Mann-Whitney U-test or Student\'s t-test, covariance analysis (ANCOVA), and multivariate linear regression were conducted. RESULTS: Patients presented on average 4.64 (1.52) risk factors. The most affected areas were the cerebellum (71%) and the brainstem (68%), and 70% of patients had white matter changes as expected for their ages. There was a significant difference in long-term memory (p <= 0.001), executive functions (p = 0.003), perception (p = 0.001), processing speed (p <= 0.001), and attention (p <= 0.001), when comparing patients and controls, with worse results for the patients. This significant difference was not maintained after an analysis of covariance, in which information processing speed was used as a control variable. Five (18%) patients showed dependence, according to the functionality scales. The presence of lesions in the thalamus was significantly related to deficits in long-term memory (p = 0.004), executive functions (p = 0.030), perception (p = 0.007), and attention (p = 0.026).Mood, disease duration, risk factor quantity, stenosis extent, and presence of white matter lesions or multiple cerebrovascular accidents had no impact on cognition. CONCLUSIONS: The sample\'s demographic, clinical, and radiological characteristics were similar to those that were previously described in the literature. Cognitive profiles following basilar artery ischemia was characterized by deficits in attention, processing speed, long-term memory, perception, and executive functions. Although previous studies have revealed poor prognosis, the patients had longer survival and more satisfying current functionality. Only the relationship between the lesion in the thalamus and the deficits in long-term memory, executive functions, perception, and attention was evident