The initial hours following an ischaemic event in the brain represent a critically important window in which therapeutic interventions to reduce neuronal damage and improve patient outcome can be made. Nevertheless, the dynamics of cerebral blood flow and oxygenation, as well as the local physiological changes, in the first few hours after reperfusion following ischaemic stroke are not well understood. In the first study, a remote filament approach was used to obtain multispectral imaging data before, during and after middle cerebral artery occlusion to investigate early changes in haemodynamic concentration of oxy-/deoxy-haemoglobin and total blood volume, in anaesthetised mice. We use immunohistochemistry to establish the extent of cortical injury and correlate the severity of damage with the change of oxygen perfusion during and after the ischaemic event. Increased numbers of platelets and activated microglia, expression of interleukin-1α, evidence of BBB breakdown and neuronal stress are all seen within the stroked hemisphere of MCAo mice and correlate with the severity of oxy-haemoglobin concentration deficit at experimental but not with the change in oxy-haemoglobin concentration during the acute stroke. In the second study, we used the same remote filament and optical imaging approach to investigate the effects of acute systemic inflammation on haemodynamics pre, during, and after induced cerebral ischaemia. We found that an acute systemic inflammatory challenge exacerbates oxy-haemoglobin deficit after 3 h of reperfusion following an ischaemic event. We investigated known pathophysiological markers to elucidate potential mechanisms that may contribute to this exacerbated oxygenation deficit and found hyper-coagulated platelets within the large and microvessels of the ipsilateral cortex. Our findings demonstrate that despite initial restoration of HbO2 supply after 30 min MCAo there is a delayed compromise that coincides with inflammatory processes that could be a future target for improved stroke outcome after thrombolysis. We also show that acute systemic inflammation exacerbates this oxy-haemoglobin deficit after an ischaemic challenge and increases pathophysiology.

Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury. Resistin treatment reduced cleaved protein level of Poly(ADP-ribose)polymerase-1 (PARP-1), a marker of cellular apoptosis, showing the anti-apoptotic activity of resistin. Resistin increased the level of phosphorylated Akt after ischemic brain injury. The neuroprotective effect of resistin was partially reversed by a PI3K inhibitor wortmannin, demonstrating that the PI3K/Akt signal pathway is involved in the anti-apoptotic mechanisms of resistin. Finally, we found that resistin treatment improved neurological function recovery at 14 days after treatment, including balance ability and muscle strength. Given these findings, resistin may have therapeutic potential for the treatment of stroke.

Saccular aneurysms are the abnormal plastic deformation of veins and arteries that can lead to lethal thrombus genesis or internal hemorrhaging. Medication and surgery greatly reduce the mortality rates, but treatment is limited by predicting who will develop aneurysms. A common location for saccular aneurysm genesis is at the main middle cerebral artery (MCA) bifurcation. The main MCA bifurcation is comprised of the M1 MCA segment, parent artery, and two M2 segments, daughter arteries. Studies have found that the lateral angle (LA) ratio of the MCA bifurcation is correlated with aneurysm formation. The LA ratio is defined as the angle between the M1 and the larger M2 divided by the angle between the M1 and the smaller M2. When the LA ratio is equal to 1, perfectly symmetrical, no aneurysms are found at the MCA bifurcation. When the LA ratio is greater than 1.6, aneurysms are commonly found at the MCA bifurcation. In the research described here, varying MCA bifurcation angles were compared to uncover any changes to fluid flow and wall shear stress that could stimulate aneurysm growth. Eight pre-aneurysm MCA bifurcation models were created in SolidWorks® using 120 degrees, 90 degrees, and 60 degrees as the angle between the M1 and the larger M2. LA ratios of 1, 1.6 and 2.2 were then used to characterize the other branch angle (60 degrees with a LA ratio of 1 was excluded). These models were imported into COMSOL Multiphysics® where the laminar fluid flow module was used to simulate non-Newtonian blood flow. Fluid flow profiles showed little to no change between the models. Shear stress changed when the LA ratio was increased, but the changed varied between the 120, 90 and 60 degree models. 120 degree models had a 3.87% decrease in max shear stress with a LA ratio of 2.2 while the 90 degree models had 7.5% decrease in max shear stress with a LA ratio of 2.2. Each daughter artery had distinct areas of high shear stress when the LA ratio equaled 1. Increasing the LA ratio or decreasing the bifurcation angle caused the areas of shear stress to merge together. Increasing LA ratio caused shear stress to decrease and spread around the MCA bifurcation. The reduction in max wall shear stress for high LA ratios supports current aneurysm genesis hypothesizes, but additional testing is required before bifurcation geometries can be used to predicted aneurysm genesis.

Dissertation (Ph.D.)--University of South Florida, 2009. / Includes vita. Includes bibliographical references. Also available online.

A introdução dos endoscópios na otorrinolaringologia determinou um grande avanço tecnológico, permitindo a sistematização da cirurgia endoscópica nasossinusal funcional. A possibilidade de trabalhar nos limites das cavidades nasossinusais com boa iluminação e visibilidade permitiu a expansão dessa cirurgia para abordar lesões da base do crânio e no interior da cavidade craniana, ampliando consideravelmente as suas indicações e a gravidade das suas complicações. Dentre estas complicações as lesões vasculares e ou de nervos cranianos estão entre as principais causas de morbidade. A artéria frontobasilar medial (AFM) é o primeiro ramo cortical do segmento pós-comunicante da artéria cerebral anterior e possui percurso próximo a base anterior do crânio. Havendo penetração intracraniana através da base anterior do crânio, durante uma cirurgia endoscópica endonasal, a AFM pode ser lesionada causando graves complicações. O objetivo deste estudo foi analisar as relações da AFM com a base anterior do crânio e reparos anatômicos utilizados em cirurgia endonasal, através de imagens obtidas por angiotomografia de crânio. E também identificar os locais de maior proximidade da AFM com a base anterior do crânio, sugerindo áreas de maior risco de lesão em cirurgia endonasal. Foram analisados 52 exames de angiotomografia de crânio, realizados no período de 2013 a 2015. O software OsiriXÒ foi utilizado para fazer as medições entre a AFM e os pontos de referência nos planos sagital e coronal, na ordem cronológica em que os exames foram coletados. A AFM descreveu um trajeto descendente, próximo a linha média (distancia média de 1,5 mm), se aproximando do plano esfenoidal (distancia média de 1,8 mm) e depois um trajeto ascendente à medida que se dirige para porção anterior do crânio, com distância média de 4,4mm na região da parede anterior do seio esfenoidal e de 12mm na região onde se encontra a artéria etmoidal anterior. Considerando o ângulo de trabalho na cirurgia endonasal e a os locais de maior proximidade da AFM com a base anterior do crânio, as regiões do etmoide posterior e plano esfenoidal foram as áreas de maior risco de sua lesão Study of the relations between medial orbitofrontal artery and anterior skull base performed by computed tomography angiography / The introduction of endoscopes in otolaryngology determined a great technological advance, allowing the systematization of the endoscopic endonasal sinus surgery. The possibility of working at the nasal cavity boundaries with good illumination and visibility allowed the expansion of this surgery to address lesions of the skull base and inside the cranial cavity, considerably broadening its indications and the severity of its complications. Among these complications, vascular lesions and cranial nerves are among the main causes of morbidity. The medial orbitofrontal artery (MOFA) the first cortical branch of the post-communicating segment of the anterior cerebral artery and has a path near the anterior skull base. If there is an intracranial penetration through the anterior skull base, during endonasal surgery, the MOFA can be injured causing serious complications. The objective of this study was to analyze the MOFA relations with the anterior skull base and anatomical repairs used in endonasal surgery, through images obtained by computed tomography angiography. And also identify the sites of greater proximity of the MOFA with the anterior skull base, suggesting areas of greater risk of injury in endonasal surgery. It was studied 52 examinations of skull computed tomography angiography performed between 2013 and 2015. The OsiriXÒ software was used to make the measurements between the MOFA and the reference points in the sagittal and coronal planes, in the chronological order in which the exams were collected. The MOFA described a descending path, close to the midline (average distance of 1.5 mm), approaching the sphenoid plane (average distance of 1.8 mm) and then an ascending path as it is directed towards the anterior portion of the skull, with an average distance of 4.4 mm in the region of the anterior wall of the sphenoid sinus and 12 mm in the region where the anterior ethmoid artery is located. Considering the angle of work in endonasal surgery and the places of greater proximity of the MOFA with the anterior skull base, the regions of the posterior ethmoid and sphenoid plane were the areas of greatest risk of its lesion

A introdução dos endoscópios na otorrinolaringologia determinou um grande avanço tecnológico, permitindo a sistematização da cirurgia endoscópica nasossinusal funcional. A possibilidade de trabalhar nos limites das cavidades nasossinusais com boa iluminação e visibilidade permitiu a expansão dessa cirurgia para abordar lesões da base do crânio e no interior da cavidade craniana, ampliando consideravelmente as suas indicações e a gravidade das suas complicações. Dentre estas complicações as lesões vasculares e ou de nervos cranianos estão entre as principais causas de morbidade. A artéria frontobasilar medial (AFM) é o primeiro ramo cortical do segmento pós-comunicante da artéria cerebral anterior e possui percurso próximo a base anterior do crânio. Havendo penetração intracraniana através da base anterior do crânio, durante uma cirurgia endoscópica endonasal, a AFM pode ser lesionada causando graves complicações. O objetivo deste estudo foi analisar as relações da AFM com a base anterior do crânio e reparos anatômicos utilizados em cirurgia endonasal, através de imagens obtidas por angiotomografia de crânio. E também identificar os locais de maior proximidade da AFM com a base anterior do crânio, sugerindo áreas de maior risco de lesão em cirurgia endonasal. Foram analisados 52 exames de angiotomografia de crânio, realizados no período de 2013 a 2015. O software OsiriXÒ foi utilizado para fazer as medições entre a AFM e os pontos de referência nos planos sagital e coronal, na ordem cronológica em que os exames foram coletados. A AFM descreveu um trajeto descendente, próximo a linha média (distancia média de 1,5 mm), se aproximando do plano esfenoidal (distancia média de 1,8 mm) e depois um trajeto ascendente à medida que se dirige para porção anterior do crânio, com distância média de 4,4mm na região da parede anterior do seio esfenoidal e de 12mm na região onde se encontra a artéria etmoidal anterior. Considerando o ângulo de trabalho na cirurgia endonasal e a os locais de maior proximidade da AFM com a base anterior do crânio, as regiões do etmoide posterior e plano esfenoidal foram as áreas de maior risco de sua lesão Study of the relations between medial orbitofrontal artery and anterior skull base performed by computed tomography angiography / The introduction of endoscopes in otolaryngology determined a great technological advance, allowing the systematization of the endoscopic endonasal sinus surgery. The possibility of working at the nasal cavity boundaries with good illumination and visibility allowed the expansion of this surgery to address lesions of the skull base and inside the cranial cavity, considerably broadening its indications and the severity of its complications. Among these complications, vascular lesions and cranial nerves are among the main causes of morbidity. The medial orbitofrontal artery (MOFA) the first cortical branch of the post-communicating segment of the anterior cerebral artery and has a path near the anterior skull base. If there is an intracranial penetration through the anterior skull base, during endonasal surgery, the MOFA can be injured causing serious complications. The objective of this study was to analyze the MOFA relations with the anterior skull base and anatomical repairs used in endonasal surgery, through images obtained by computed tomography angiography. And also identify the sites of greater proximity of the MOFA with the anterior skull base, suggesting areas of greater risk of injury in endonasal surgery. It was studied 52 examinations of skull computed tomography angiography performed between 2013 and 2015. The OsiriXÒ software was used to make the measurements between the MOFA and the reference points in the sagittal and coronal planes, in the chronological order in which the exams were collected. The MOFA described a descending path, close to the midline (average distance of 1.5 mm), approaching the sphenoid plane (average distance of 1.8 mm) and then an ascending path as it is directed towards the anterior portion of the skull, with an average distance of 4.4 mm in the region of the anterior wall of the sphenoid sinus and 12 mm in the region where the anterior ethmoid artery is located. Considering the angle of work in endonasal surgery and the places of greater proximity of the MOFA with the anterior skull base, the regions of the posterior ethmoid and sphenoid plane were the areas of greatest risk of its lesion

ABBREVIATIONS A – amniocentesis DA – deceleration angle FMH – fetomaternal haemorrhage MCA – middle cerebral artery MoM – multiples of median PI – pulsatility index PSV – peak systolic velocity RI – resistance index SA – splenic artery SGA – small for gestational age HDN – haemolytic disease of newborn 1. INTRODUCTION Rhesus alloimmunization occurs when a rhesus negative woman has an immunologic response to a paternally derived red-cell antigen that is foreign to the mother and inherited by the fetus. Rhesus alloimmunization and haemolytic disease of the newborn continues to occur as a serious complication of pregnancy despite well-organized antenatal antiD prophylaxis programs. At the Perinatal Center of Kaunas University of Medicine the incidence has remained stable at around 60 cases of alloimmunized pregnancies and from 30 to 40 cases of haemolytic disease of newborn annually. Perinatal mortality in cases of rhesus alloimmunization has been estimated to be at around 1 to 3.5 percent. Due to failure to apply or comply with antiD prophylaxis guidelines and limitations of the prophylaxis rhesus sensitization continues to occur. Rhesus alloimmunization is diagnosed when the test of a rhesus negative woman for red cell alloantibodies is positive. Prognosis for the fetus and perinatal outcomes depends much on how severely the fetus is affected by the disease at the time of diagnosis. The main pathological entity of the disease is fetal red blood cell destruction and... [to full text]

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Sabe-se que um bom fluxo sanguíneo colateral (FSC) leptomeníngeo está associado a melhor desfecho funcional em paciente com oclusão vascular da circulação anterior. Entretanto, poucos estudos avaliaram os preditores de FSC e seu impacto prognósticos em países em desenvolvimento. O objetivo deste trabalho é avaliar os preditores e o impacto prognóstico do FSC leptomeníngeo nas oclusões do primeiro segmento (M1) da Artéria Cerebral Média (ACM). Métodos: Foi avaliado de maneira retrospectiva, uma coorte prospectiva de pacientes com acidente vascular cerebral (AVC), admitidos em um centro terciário acadêmico de referência para o tratamento de AVC entre janeiro de 2014 e junho de 2017. Foram incluídos pacientes que apresentavam oclusão do segmento M1 da ACM e realizaram angiotomografia de crânio (AngioTC) até 12 horas após o ictus. O FSC foi analisado utilizando uma escala previamente validada na literatura, o rLMC score. Foi avaliado a relação do rLMC score com variáveis clínicas e com desfecho. Na análise univariada foi utilizado o teste de Fisher para variáveis categóricas e t de Student para variáveis quantitativas, também foi utilizado o teste de Spearman para correlação de variáveis contínuas. Características associadas com rLMC score e com desfecho funcional foram incluídas da regressão linear (rLMC não categorizado) e regressão logística binária (rLMC categorizado). Foi utilizado um valor de significância estatística convencional (p=0,05) Resultados: Dos 1559 pacientes com AVC isquêmico admitidos, foram analisados 121 pacientes que preencheram critérios de inclusão/exclusão do estudo. A idade média foi de 67.1±15 anos, NIHSS 13 [IQR 11-22]. Na regressão linear, menor idade (? = -0.2; p=0.005), Doença de14 Chagas (? = 0,22; p=0,008), Tabagismo (? = 0,22; p=0,009), menor NIHSS (? = - 0,25; p=0,002) e história de doença coronariana (? = 0,23; p=0,005) foram associados com melhor rLMC score. Menor idade (? = 0,29; p<0,001), menor NIHSS (? = 0,36; p<0,001) e rLMC>= 17 (? = -0,16; p=0,04) foram associados com melhor desfecho clínico. Conclusão: Pacientes com bom FSC leptomeníngeo apresentam menor NIHSS, menor idade, maior frequência de doença de Chagas, história de tabagismo e doença coronariana prévia. Um bom FSC leptomeníngeo está associado a melhor desfecho funcional entre paciente com AVC isquêmico por oclusão de artérias proximais da circulação anterior no Brasil. / A Good leptomeningeal collateral flow has been associated with better outcomes in patients with proximal occlusions of the anterior circulation. Nevertheless, only few studies have assessed the predictors of good leptomeningeal collateral flow and its impact on clinical outcome in developing countries. We aim to evaluate predictors and prognostic impact of leptomeningeal collateral flow among patients with proximal middle cerebral artery (MCA) occlusion. Method: We retrospectively analyzed a prospective stroke registry of AIS patients admitted to a tertiary Stroke Center in Brazil, with MCA-M1 occlusion within twelve hours of symptoms onset, admitted from January 2014-June 2017. Leptomeningeal score was evaluated using a previously validated Regional Leptomeningeal (rLMC) score. We evaluated association between rLMC score with clinical variables and outcomes. Univariate analysis was performed using Fisher exact test for categorical variables and t-Student for continuous variables. Spearman\'s correlation analysis was performed to find the relationship between continuous variables and rLMC. Variables were included in linear regression model (non categorized rLMC) or binary logistic regression model (categorized rLMC). Conventional levels of statistical significance were used (p=0.05). Results: From 1559 AIS patients, 121 were analyzed. Demographics: age 67.1±15 years, NIHSS 13 [IQR 11-22]. In linear regression, lower age (? = -0.2; p=0.021), Chagas Disease (? = 0.22; p=0.008), smoking (? = 0.22; p=0.009), lower NIHSS (? = -0.25; p=0.002) and history of coronary artery disease (? = 0.23; p=0,005) were associated with better rLMC score. Lower age (? = 0.29; p<0.001), lower NIHSS (? = 0.36; p<0.001) and rLMC>= 17 (? = -0.16; p=0.04) were associated with better functional outcomes. Conclusion: Patients with good leptomeningeal collateral flow had lower age, lower NIHSS, Chagas disease and history of smoking. Good leptomeningeal collaterals on CT angiography are associated to good outcome among AIS patients with proximal arterial occlusion of the anterior circulation in Brazil.