Many populations have low intakes of n-3 fatty acids, yet there is substantial evidence that the long chain n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3), found at high concentrations in the brain, is required for the proper development of the nervous system. However, less is known about requirements of long chain n-3 fatty acids for maintenance and function of the nervous system in later life. Several recent studies have reported that high amounts of long chain n-3 fatty acids reduce the extent of brain damage caused by cerebral ischemia in animals. However, whether or not a dietary deficiency of n-3 fatty acids increases the extent of injury when cerebral ischemia occurs has not been previously reported. The present studies, therefore, sought to determine if a diet deficient in n-3 fatty acids influences the extent of brain injury in the rat following cerebral ischemia. Male rats were fed an n-3 fatty acid adequate (control), an n-3 fatty acid deficient, or a high DHA diet for 5 weeks from weaning. Middle cerebral artery occlusion (MCAO) was induced and infarct volume was measured by 2,3,5,-triphenyltetrazolium chloride staining 24 hours after the procedure. Brain and platelet fatty acids were analyzed by gas liquid chromatography. DHA (22:6n-3) was 21-28% lower in brain phospholipids, and 17% lower in brain total fatty acids in the n-3 fatty acid deficient compared to control group, while 22:6n-3 was 12% higher in total brain fatty acids in the high DHA group than the control group. There was no significant difference in infarct volume (203, 220 and 218 mm³) among the control, n-3 fatty acid deficient, and high DHA groups, respectively. Platelet fatty acids and platelet aggregation were assessed to determine if these were influenced by the high DHA diet, and could possibly explain the observation of an apparent, but not statistically significant, higher number of rats with hemorrhages in the high DHA diet group. Platelet lipid arachidonic acid was not lower and platelet aggregation, assessed ex vivo using whole blood with a platelet function analyzer, was not longer in rats fed the high DHA compared to control or n-3 fatty acid deficient diets. In summary, dietary n-3 fatty acid deficiency did not increase the extent of brain injury following cerebral ischemia. The possibility that high dietary 22:6n-3 might increase susceptibility to cerebral hemorrhage will require further study.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Made available in DSpace on 2015-12-06T23:05:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2005 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundo de Auxílio aos Docentes e Alunos (FADA) / Objetivo: Este estudo piloto procurou revisar a metodologia e discutir a aplicação da Terapia por Contensão Induzida (TCI) nos pacientes com acidente vascular cerebral isquêmico (AVCI) crônico, em um centro de reabilitação brasileiro. Método: Uma ampla revisão da literatura médica foi realizada para adaptar esta técnica em nosso meio. Foram selecionados 10 pacientes que se submeteram a 6 horas de tratamento por duas semanas consecutivas. Entre os critérios de seleção destacam-se AVCI em território da artéria cerebral média. Nestes 14 dias os pacientes foram submetidos a atividades motoras repetitivas utilizando o membro superior parético, enquanto o membro não parético era mantido com um dispositivo de contenção. Resultados: Houve melhora significativa no déficit motor do membro superior parético e concomitante melhora na resposta ao Teste de Função Motora de Wolf. Conclusão: Esta nova técnica de reabilitação específica para pacientes com déficit motor moderado em membro superior parético é viável em nosso país. Nosso estudo sugere que a dominância e tempo de lesão têm um efeito modificador sobre o tratamento em pacientes com lesão isquêmica crônica no território da artéria cerebral média. / Purpose: The purpose of this pilot study is to review evidence and discuss the aplly of Constraint Induced Movement Therapy (CIMT) protocol in a brazilian center of rehabilitation in chronic patients with isquemic stroke. Methods: A wide revision of the medical literature was accomplished to adapt this technique for our population. Ten patients were selected and submitted at 6 hours of treatment for 2 weeks. Among the selection criteria they stand out schemic stroke in the middle cerebral artery territorry. On these 14 days the patients were submitted to repetitive motor activities using the paretic upper-limb while the unaffected limb was maintained with a constraint device. Results: There was a significant improvement of function of the affected upper-limb in the motor deficit of the paretic upper-limb and concomitant improvement in the answer to the Wolf Motor Function Test. Conclusions: This new technique of specific rehabilitation for patients with moderate motor deficit in paretic upper limb is feasible in Brazil. Our study suggest that the dominance and the time of lesion have a modifier effect on the treatment in patients with chronic schemic lesion in the middle cerebral artery territory. / BV UNIFESP: Teses e dissertações

O contexto do estudo é a predição da anemia fetal em gestantes portadoras da doença hemolítica perinatal e tem como objetivo avaliar a acurácia da medida doppler velocimétrica da velocidade máxima do pico sistólico da artéria cerebral média na detecção da anemia fetal na doença hemolítica perinatal. A identificação dos estudos foi realizada com a adoção de bancos de dados gerais (MEDLINE e LILACS) e a partir de referências bibliográficas de outros autores. Os estudos selecionados tinham como critérios serem do tipo observacionais, com gestantes apresentando coombs indireto maior do que 1:8, técnica de insonação do vaso adequada, Vmax-ACM ≥ 1,5MOM, presença obrigatória de comparação com o padrão-ouro (hemoglobina fetal e/ou neonatal), e nível de evidência diagnóstica acima ou igual a 4. Os dados dos estudos selecionados foram alocados em tabelas 2x2 comparando o resultado do teste com o padrão-ouro. A acurácia diagnóstica foi expressa principalmente através da razão de verossimilhança. A revisão incluiu onze estudos, com uma amostra total de 688. Três estudos apresentaram delineamento do tipo prospectivo e nível de evidência diagnóstica categoria 1. A performance do teste em questão apresentou variação razoável. O estudo de Mari et al (2000) foi considerado o de melhor qualidade metodológica, apresentando uma RV(+) de 8,45 e uma RV(-) de 0,02. A medida do doppler da Vmax da ACM como preditor da anemia fetal na doença hemolítica perinatal está consolidada. Porém, alguns pontos precisam ser melhor esclarecidos, como o intervalo ideal dos exames em casos graves e a validade do método em fetos que já foram submetidos a transfusões intra-uterinas. / Study context is the prediction of fetal anemia in pregnant women with perinatal haemolitical disease and it has like objective to appraise the accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) in fetal anemia prediction. Papers identification was identified using general bibliographic databases (MEDLINE and LILACS), and by checking reference lists of other authors. Studies were selected if observe type, pregnant woman with indirect coombs higher than 1:8, adequate technic, MCA-PSV ≥ 1,5MOM, presence of gold standard (fetal or newborn hemoglobin), and hierarchy of evidence higher or equal than four. Data from the selected studies were abstracted as 2 x 2 tables comparing the diagnostic teste result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios. The review included eleven studies with a total sample of 688. Prospective patient recruitment and hierarchy of evidence one were reported in three studies. The test performance presented reasonable variation. Mari et al (2000) study was applied like best quality, with a LR(+) 8,45 and LR(-) 0,02. MCA-PSV like a fetal anemia predictor in perinatal haemolitical disease is consolidated. However, some points have to be cleared up., like the best exams interval in severe cases and method validity in after transfusional situation.

O contexto do estudo é a predição da anemia fetal em gestantes portadoras da doença hemolítica perinatal e tem como objetivo avaliar a acurácia da medida doppler velocimétrica da velocidade máxima do pico sistólico da artéria cerebral média na detecção da anemia fetal na doença hemolítica perinatal. A identificação dos estudos foi realizada com a adoção de bancos de dados gerais (MEDLINE e LILACS) e a partir de referências bibliográficas de outros autores. Os estudos selecionados tinham como critérios serem do tipo observacionais, com gestantes apresentando coombs indireto maior do que 1:8, técnica de insonação do vaso adequada, Vmax-ACM ≥ 1,5MOM, presença obrigatória de comparação com o padrão-ouro (hemoglobina fetal e/ou neonatal), e nível de evidência diagnóstica acima ou igual a 4. Os dados dos estudos selecionados foram alocados em tabelas 2x2 comparando o resultado do teste com o padrão-ouro. A acurácia diagnóstica foi expressa principalmente através da razão de verossimilhança. A revisão incluiu onze estudos, com uma amostra total de 688. Três estudos apresentaram delineamento do tipo prospectivo e nível de evidência diagnóstica categoria 1. A performance do teste em questão apresentou variação razoável. O estudo de Mari et al (2000) foi considerado o de melhor qualidade metodológica, apresentando uma RV(+) de 8,45 e uma RV(-) de 0,02. A medida do doppler da Vmax da ACM como preditor da anemia fetal na doença hemolítica perinatal está consolidada. Porém, alguns pontos precisam ser melhor esclarecidos, como o intervalo ideal dos exames em casos graves e a validade do método em fetos que já foram submetidos a transfusões intra-uterinas. / Study context is the prediction of fetal anemia in pregnant women with perinatal haemolitical disease and it has like objective to appraise the accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) in fetal anemia prediction. Papers identification was identified using general bibliographic databases (MEDLINE and LILACS), and by checking reference lists of other authors. Studies were selected if observe type, pregnant woman with indirect coombs higher than 1:8, adequate technic, MCA-PSV ≥ 1,5MOM, presence of gold standard (fetal or newborn hemoglobin), and hierarchy of evidence higher or equal than four. Data from the selected studies were abstracted as 2 x 2 tables comparing the diagnostic teste result with the reference standard. Diagnostic accuracy was expressed as likelihood ratios. The review included eleven studies with a total sample of 688. Prospective patient recruitment and hierarchy of evidence one were reported in three studies. The test performance presented reasonable variation. Mari et al (2000) study was applied like best quality, with a LR(+) 8,45 and LR(-) 0,02. MCA-PSV like a fetal anemia predictor in perinatal haemolitical disease is consolidated. However, some points have to be cleared up., like the best exams interval in severe cases and method validity in after transfusional situation.

Many populations have low intakes of n-3 fatty acids, yet there is substantial evidence that the long chain n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3), found at high concentrations in the brain, is required for the proper development of the nervous system. However, less is known about requirements of long chain n-3 fatty acids for maintenance and function of the nervous system in later life. Several recent studies have reported that high amounts of long chain n-3 fatty acids reduce the extent of brain damage caused by cerebral ischemia in animals. However, whether or not a dietary deficiency of n-3 fatty acids increases the extent of injury when cerebral ischemia occurs has not been previously reported. The present studies, therefore, sought to determine if a diet deficient in n-3 fatty acids influences the extent of brain injury in the rat following cerebral ischemia. Male rats were fed an n-3 fatty acid adequate (control), an n-3 fatty acid deficient, or a high DHA diet for 5 weeks from weaning. Middle cerebral artery occlusion (MCAO) was induced and infarct volume was measured by 2,3,5,-triphenyltetrazolium chloride staining 24 hours after the procedure. Brain and platelet fatty acids were analyzed by gas liquid chromatography. DHA (22:6n-3) was 21-28% lower in brain phospholipids, and 17% lower in brain total fatty acids in the n-3 fatty acid deficient compared to control group, while 22:6n-3 was 12% higher in total brain fatty acids in the high DHA group than the control group. There was no significant difference in infarct volume (203, 220 and 218 mm³) among the control, n-3 fatty acid deficient, and high DHA groups, respectively. Platelet fatty acids and platelet aggregation were assessed to determine if these were influenced by the high DHA diet, and could possibly explain the observation of an apparent, but not statistically significant, higher number of rats with hemorrhages in the high DHA diet group. Platelet lipid arachidonic acid was not lower and platelet aggregation, assessed ex vivo using whole blood with a platelet function analyzer, was not longer in rats fed the high DHA compared to control or n-3 fatty acid deficient diets. In summary, dietary n-3 fatty acid deficiency did not increase the extent of brain injury following cerebral ischemia. The possibility that high dietary 22:6n-3 might increase susceptibility to cerebral hemorrhage will require further study. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

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.