Progressive degeneration in the central nervous system (CNS) of Huntington’s disease (HD) patients is a relentless debilitating process, resulting from the inheritance of a single gene mutation. With limited knowledge of the underlying pathological molecular mechanisms, pharmaceutical intervention has to-date not provided any effective clinical treatment strategies to attenuate or compensate the neuronal cell death. Attention has therefore turned to biotherapeutic molecules and novel treatment approaches to promote restoration and protection of selectively vulnerable populations of neurons in the HD brain. Rapid advances in vectorology and gene-based medicine over the past decade have opened the way for safe and efficient delivery of biotherapeutics to the CNS. With numerous factors known to regulate the development, plasticity and maintenance of the mammalian nervous system many proteins have emerged as potential therapeutic agents to alleviate HD progression. This investigative study utilised gene delivery vectors derived from the non-pathogenic adeno-associated virus (AAV) to direct high-level expression of brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), Bcl-xL or X-linked inhibitor of apoptosis protein (XIAP) within the rodent striatum. Maintenance of the basal ganglia and functional behaviour deficits were assessed following excitotoxic insult of the striatum by quinolinic acid (QA), a neurotoxic model of HD pathology. Enhanced striatal expression of BDNF prior to QA-induced lesioning provided maintenance of the striosome-matrix organisation of the striatum, attenuating impairments of sensorimotor behaviour with a 36-38% increase in the maintenance of DARPP-32 / krox-24 expressing striatal neurons, reduced striatal atrophy and increased maintenance of striatonigral projections. Higher levels of BDNF however induced seizures and weight-loss highlighting the need to provide regulatable control over biotherapeutic protein expression. Continuous high-expression of BDNF or GDNF resulted in a downregulation of intracellular signal mediating proteins including DARPP-32, with AAV-GDNF not found to enhance the overall maintenance of striatal neurons. Neither of the anti-apoptotic factors provided significant protection of transduced striatal neurons but tended towards ameliorating QA-induced behavioural deficits, displaying behaviour – pathology correlations with the survival of parvalbumin-expressing neurons in the globus pallidus. The results of this thesis suggest BDNF as a promising putative biotherapeutic for HD, but emphasises the requirement to control expression following gene delivery, and for further elucidation of the physiological impact that enhanced expression of endogenous factors has on the host cells. Additionally the maintenance of neural networks beyond the caudate-putamen will be vital to ensuring efficient clinical outcomes for HD. / Auckland Medical Research Foundation. Foundation for Research, Science and Technology. The University of Auckland.

Progressive degeneration in the central nervous system (CNS) of Huntington’s disease (HD) patients is a relentless debilitating process, resulting from the inheritance of a single gene mutation. With limited knowledge of the underlying pathological molecular mechanisms, pharmaceutical intervention has to-date not provided any effective clinical treatment strategies to attenuate or compensate the neuronal cell death. Attention has therefore turned to biotherapeutic molecules and novel treatment approaches to promote restoration and protection of selectively vulnerable populations of neurons in the HD brain. Rapid advances in vectorology and gene-based medicine over the past decade have opened the way for safe and efficient delivery of biotherapeutics to the CNS. With numerous factors known to regulate the development, plasticity and maintenance of the mammalian nervous system many proteins have emerged as potential therapeutic agents to alleviate HD progression. This investigative study utilised gene delivery vectors derived from the non-pathogenic adeno-associated virus (AAV) to direct high-level expression of brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), Bcl-xL or X-linked inhibitor of apoptosis protein (XIAP) within the rodent striatum. Maintenance of the basal ganglia and functional behaviour deficits were assessed following excitotoxic insult of the striatum by quinolinic acid (QA), a neurotoxic model of HD pathology. Enhanced striatal expression of BDNF prior to QA-induced lesioning provided maintenance of the striosome-matrix organisation of the striatum, attenuating impairments of sensorimotor behaviour with a 36-38% increase in the maintenance of DARPP-32 / krox-24 expressing striatal neurons, reduced striatal atrophy and increased maintenance of striatonigral projections. Higher levels of BDNF however induced seizures and weight-loss highlighting the need to provide regulatable control over biotherapeutic protein expression. Continuous high-expression of BDNF or GDNF resulted in a downregulation of intracellular signal mediating proteins including DARPP-32, with AAV-GDNF not found to enhance the overall maintenance of striatal neurons. Neither of the anti-apoptotic factors provided significant protection of transduced striatal neurons but tended towards ameliorating QA-induced behavioural deficits, displaying behaviour – pathology correlations with the survival of parvalbumin-expressing neurons in the globus pallidus. The results of this thesis suggest BDNF as a promising putative biotherapeutic for HD, but emphasises the requirement to control expression following gene delivery, and for further elucidation of the physiological impact that enhanced expression of endogenous factors has on the host cells. Additionally the maintenance of neural networks beyond the caudate-putamen will be vital to ensuring efficient clinical outcomes for HD. / Auckland Medical Research Foundation. Foundation for Research, Science and Technology. The University of Auckland.

Thesis (Ph.D.); Submitted to Iowa State Univ., Ames, IA (US); 12 Dec 2003. / Published through the Information Bridge: DOE Scientific and Technical Information. "IS-T 2604" Jason Alan Gruenhagen. 12/12/2003. Report is also available in paper and microfiche from NTIS.

Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 4 uppsatser.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Depression and stimulant drug addiction each result in massive losses of health, productivity and human lives every year. Despite decades of research, current treatment regimes for depression are ineffective in approximately half of all patients. Therapy available to stimulant drug addicts is largely ineffective and moreover, dedicated treatments for drug dependence (including abuse of cocaine) are non-existent. Thus, there is a pressing need to further understanding of the molecular mechanisms underlying these disorders in order to develop novel, targeted therapeutic strategies. Chromatin remodeling, including changes in histone acetylation, has been proposed to play a role in both the etiology and treatment of depression and stimulant abuse. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate numerous cellular processes, including transcription, cell cycle progression and differentiation. Moreover, histone acetylation has been shown to regulate hippocampal neurogenesis, a cellular response associated with the pathogenesis and treatment of depression and stimulant abuse (Hsieh et al., 2004, Yamaguchi et al., 2004, Fischer et al., 2007). Ultimately, such basic cellular processes impact higher order function, namely cognition and emotion. Indeed, recent studies suggest that HDAC activity in selected forebrain regions, including ventral striatum and hippocampus, modulate stimulant- and antidepressantinduced behavior (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). These reports highlight an association between chromatin remodeling and diverse behavioral changes, including changes induced by the pleiotropic HDAC inhibitor, sodium butyrate (SB), (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). However, behavioral, brain-metabolic and molecular effects of SB treatment in the context of rodent models of depression, dopaminergic sensitization and repeated cocaine administration remained unclear. The work described in this thesis illustrates the potential for chromatin modifying drugs in mechanisms underlying the experimental pharmacology of depression and stimulant addiction. Specifically, the data presented here support the view that treatment with the short chain fatty acid, sodium butyrate enhances: (1) antidepressant-like behavioral effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (2) locomotor sensitization induced by repeated administration of the dopamine D1/D5 receptor agonist SKF82958; and(3) brain metabolic activation upon repeated cocaine administration as evidenced by fMRI in awake rats. Furthermore, this report provides evidence that these treatment paradigms will result in chromatin modification changes associated with active transcription, in addition to increased mRNA levels of plasticity-associated genes, including brain-derived neurotrophic factor (BDNF) at key brain regions implicated in the pathogenesis of depression and stimulant addiction. To date, little is known regarding the underlying mechanisms of action mediating the enhancing effects of sodium butyrate on the various antidepressant- and stimulantrelated paradigms. Our findings underscore the potential of chromatin-modifying drugs to profoundly affect the behavioral response of an animal to antidepressant and stimulant drugs and warrants consideration in the context of developing novel therapeutic strategies.

Made available in DSpace on 2015-07-22T20:50:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-22. Added 1 bitstream(s) on 2015-08-11T03:26:13Z : No. of bitstreams: 1 Publico-12887.pdf: 1856396 bytes, checksum: 42de9f60d780e16634f25ebf960a3c24 (MD5) / Lesões no sistema nervoso central (SNC) levam a permeabilidade da barreira hematoencefálica, o que permite a entrada de células do sistema imune e a ativação das células da glia, principalmente microglia e astrócitos. Esse processo desencadeia a secreção de mediadores inflamatórios por essas células. As citocinas são as principais moléculas da resposta neuroinflamatória e são críticas para a regulação desta resposta, exercendo uma variedade de ações no SNC. Células tronco mesenquimais (CTMs), que possuem potencial proliferativo e são capazes de originar linhagens celulares distintas e especializadas, também secretam essas moléculas, caracterizando um poder imunomodulador. As CTMs, particularmente as derivadas da medula óssea, promovem o reparo tecidual pela secreção de fatores que aumentam a regeneração do tecido, estimulando proliferação, migração e diferenciação de progenitores endógenos encontrados na maioria dos tecidos, diminuindo a resposta imune e inflamatória e a apoptose. A habilidade de essas células alterarem o microambiente através de sua influência trófica pode contribuir mais significativamente para o reparo do tecido que a transdiferenciação. Nossa hipótese é que as citocinas secretadas pelas CTMs poderiam participar da atração de células tronco neurais endógenas para um local de lesão no SNC, criando um microambiente favorável para essas células. Tendo isso em vista, esta tese teve como objetivo estudar os efeitos dos fatores secretados pelas CTMs sobre células tronco neurais (CTNs) in vitro, e analisar a expressão de citocinas por CTMs in vivo em um modelo de lesão traumática no SNC. Primeiramente, avaliamos os efeitos dos fatores secretados pelas CTMs sobre apoptose, proliferação e diferenciação de CTNs adultas derivadas da zona subventricular e cultivadas como neuroesferas. Para isso, cultivamos as neuroesferas em meio condicionado por CTMs derivadas de medula óssea. Além disso, foram realizadas lesões no córtex motor primário dos animais, seguidas da injeção de CTMs no local da lesão. Nossos resultados indicam que os fatores secretados pelas CTMs não induzem nem previnem a apoptose das CTNs, aumentam a proliferação dessas células e induzem maior expressão do gene GFAP in vitro, o que indicaria uma tendência a diferenciação em astrócitos. Nos experimentos in vivo, nossos resultados mostram que a injeção das CTMs em um modelo de lesão aguda no SNC diminui a expressão de citocinas pró-inflamatórias no tecido lesado, indicando que os fatores solúveis secretados por CTMs podem modular a inflamação no local lesado, o que pode ser interessante para a criação de um microambiente favorável para CTNs endógenas e conseqüentemente para o reparo do tecido lesado. / Central nervous system (CNS) injury breakes the impermeability of the blood brain barrier, this allows the invasion of immune cells and activation of glial cells, mainly microglia and astrocytes. This process triggers the secretion of inflammatory mediators by these cells. Cytokines are the main molecules in neuroinflammatory response and are critical for its regulation, exerting a variety of actions in the CNS. Furthermore, mesenchymal stem cells (MSC) which have proliferative potential and are able to originate different and specialized cell lineages, also secrete these molecules, characterizing its immunomodulatory function. MSC, particularly those derived from bone marrow, promote tissue repair by secreting factors that enhance tissue regeneration stimulating proliferation, migration and differentiation of endogenous stem-like progenitors found in most tissues, decreasing inflammatory and immune reactions and apoptosis. The ability of such cells to alter tissue microenvironment through its trophic influence may contribute more significantly than their capacity for transdifferentiation in effecting tissue repair.Our hypothesis is that MSC secreted cytokines could take part in the attraction of endogenous neural stem cells (NSC) to an injury site in the CNS, providing a favorable microenvironment for these cells. Our aim was to study the effects of factors secreted by MSC on NSC in vitro and to analyse the MSC cytokines expression in vivo in a model of CNS traumatic injury. We first evaluated the effects of MSC secreted factors on apoptosis, proliferation and differentiation of adult NSC derived from the subventricular zone and cultured as neurospheres. Neurospheres were cultured in MSC conditioned medium (MSC-CM), which was obtained from bone marrow-derived MSC cultures. Besides a traumatic injury was performed at the primary motor cortex of mice and MSCs were injected at the injury site. Our results show that MSC secreted factors do not induce or prevent NSC apoptosis, increase NSC proliferation and induce bigger expression of GFAP gene in vitro, this could indicate a tendency of differentiation to astrocytes. In vivo experiments show that MSC injection at an acute model of injury diminishes pro-inflamatory cytokines in the injured tissue, suggesting that MSC secreted factors may modulate the inflammation at the injury site, which may be interest to the development favorable microenvironment for endogenous NSC and consequently repair of the injured tissue. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2014-06-11T19:22:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-25Bitstream added on 2014-06-13T20:10:19Z : No. of bitstreams: 1 jacob_cro_me_rcla.pdf: 1789232 bytes, checksum: 4d1aeb62cf1a6763869b8890da8b652a (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Recentemente as abelhas têm sido devidamente valorizadas como importantes polinizadoras de flores silvestres e cultivadas. A densidade populacional de muitos polinizadores tem diminuído devido, principalmente, à intensificação agrícola e ao uso de pesticidas, prejudicando os serviços de polinização. A metodologia clássica para estimar a toxicidade dos produtos químicos para insetos é determinar a dose letal média (DL50) ou a concentração letal média (CL50), podendo então estabelecer doses que sejam mais seguras aos organismos não-alvo ou benéficos. Além dos efeitos de toxicidade aguda, levando a morte das abelhas, doses subletais dos inseticidas podem provocar alterações comportamentais e fisiológicas nos indivíduos, que ao longo do tempo acarretarão em sérios prejuízos na manutenção da colônia. Um dos inseticidas amplamente utilizado é o fipronil, este atua ligando-se aos receptores do ácido gama-aminobutírico (GABA), interrompendo os canais de cloro, resultando na perda de sinalização inibitória neural. Na literatura pode-se encontrar diversos trabalhos que utilizam como modelo principal a abelha Apis mellifera, porém, é importante ressaltar a diversidade existente entre as abelhas nativas no Brasil, os meliponíneos, e sua participação na conservação da biodiversidade, assim como na polinização de áreas de cultivo, o que torna extremamente importante estudos com essa abelha. Com a finalidade de entender como o fipronil interfere morfo e fisiologicamente em abelhas sem ferrão, a região de interesse deste estudo foram os corpos pedunculados, já que estes são centros cerebrais complexos e tidos como local de convergência multisensorial. Para auxiliar no mapeamento metabólico, utilizou-se como marcador a enzima citocromo oxidase e a enzima caspase-3, técnicas utilizadas na observação de atividade neural... / A few decades the bees are considered an important indicator of high environmental sensitivity, and appreciated as important pollinators of wildflowers and cultivated. The population density of many pollinators have declined to harmful levels to pollination services manly due to agricultural intensification and the use of pesticides. The classic methodology of estimating the effects of chemicals for insects is to determine the median lethal dose (LD50) or median lethal concentration (LC50) that can then establish doses that do not harm non-target organisms or beneficial. Besides the effects of acute toxicity, leading to death bees, sublethal doses of insecticides can cause physiological and behavior changes of individuals over time, resulting in serious harm to maintain the colony. One of the widely used insecticides is fipronil, its acts by binding to gamma-aminobutyric acid (GABA) disrupting chloride channels, resulting in loss of inhibitory neural signaling. In the literature one can find several works using as main bee model Apis mellifera, however, it is important to highlight the diversity of Brazilian native bees, the stingless bees, and their participation in biodiversity conversation, as well as in the pollination of cultivated land. In order to understand how fipronil affect morpho and physiologically the stingless bee S. postica, the region of interest in this study were the mushroom bodies, since these are complex brain centers and used as a place of multisensory convergence. This work established the contact LD50 and Ingestion LC50 to the fipronil insecticide for foragers workers stingless bee Scaptotrigona postica in 0.54ng/bee and 0.24ng/μL of the food after 24 hours, respectively, confirming the high toxicity of this phenylpyrazole, in the groups submitted to contact contamination, were identify morphological... (Complete abstract click electronic access below)

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The fatty acids (FA) are important constituents of brain phospholipid membranes and play important roles in the central nervous system (CNS) may modify the plasticity and fluidity, and act decisively in the development of cognitive and neuropsychiatric disorders. During the last decades, we observed changes in eating habits, which enabled increased consumption of trans fatty acids at the expense of consumption of polyunsaturated fatty acids (PUFA), especially omega-3. Furthermore, frequent situations of stress due to pressure of the outside world may also be associated with the development of diseases involving CNS and changes in metabolic function, particularly in the metabolism of fatty acids. In this study, two sequential generations of rats were supplemented with soybean oil (C-SO), fish oil (FO) and hydrogenated vegetable fat (HVF) during pregnancy and lactation. At 41 days of age, half of the male animals of each group were exposed to acute stress (AE-2h) and evaluated in the open field and elevated plus maze, followed by euthanasia for biochemical analysis. The HVF supplemented group had higher anxiety symptoms, while groups C-SO and FO did not show these behaviors. Among the groups exposed to AE, the HVF showed greater locomotion and symptoms similar to anxiety, but this was not observed in the FO. Biochemical analyzes showed higher levels of lipid peroxidation and reduced cell viability in the cortex of HVF group. Furthermore, the HVF treated rats showed reduced catalase activity in the striatum and hippocampus, and increased generation of reactive species in the striatum, while FO was associated with increased cell viability in the hippocampus. Among the groups exposed to AE, the HVF group showed increased generation of reactive species in the brain, decreased cell viability in the cortex and striatum, and decreased catalase activity in the striatum and hippocampus. The results show that the presence of FA for the development and growth over two generations is capable of modifying parameters of oxidative status and behavior of the brain. Taken together, our data support the idea that regular consumption of a diet rich in monounsaturated fatty acids (MUFA) and PUFA, and particularly low in processed foods, can help prevent the development of emotional disorders, and suggest the influence harmful consumption of trans fat over generations, which is able to increase parameters of emotion and nervousness after stressful situations of everyday life can trigger neurological and neuropsychiatric conditions more severe. / Os ácidos graxos (AG) são constituintes importantes das membranas fosfolipídicas cerebrais e desempenham importantes funções no sistema nervoso central (SNC) podendo modificar a plasticidade e fluidez, além de atuar de forma decisiva no desenvolvimento de patologias cognitivas e neuropsiquiátricas. Durante as últimas décadas, foram observadas mudanças nos hábitos alimentares, as quais possibilitaram o aumento do consumo de ácidos graxos trans, em detrimento do consumo de ácidos graxos poliinsaturados (AGPI), principalmente o ômega-3. Além disso, situações frequentes de estresse devido a pressão do mundo exterior também podem estar associadas com o desenvolvimento de doenças que envolvem o SNC e alterações na função metabólica, particularmente no metabolismo dos ácidos graxos. Neste estudo, duas gerações sequenciais de ratas foram suplementadas com óleo de soja (C-OS), óleo de peixe (OP) e gordura vegetal hidrogenada (GVH) durante a gestação, lactação e após o desmame. Aos 41 dias de idade, parte dos animais machos, da segunda geração, foram expostos ao estresse agudo (EA-2h), enquanto a outra metade foi utilizada como controles, e avaliados em campo aberto e labirinto em cruz elevado, seguido por eutanásia para análises bioquímicas. O grupo suplementado com GVH, não expostos ao estresse, apresentou maiores sintomas de ansiedade, enquanto os grupos C-OS e OP não mostraram esses comportamentos. Entre os grupos expostos ao EA, o GVH mostrou maior locomoção e sintomas semelhantes à ansiedade, mas isso não foi observado no grupo OP. As análises bioquímicas mostraram níveis mais elevados de peroxidação lipídica e menor viabilidade celular no córtex do grupo GVH. Além disso, os ratos tratados com GVH mostraram reduzida atividade da catalase no estriado e hipocampo, bem como aumento da geração de espécies reativas no estriado, ao passo que OP foi associado com aumento da viabilidade celular no hipocampo. Entre os grupos expostos ao EA, o grupo GVH mostrou aumento da geração de espécies reativas no cérebro, diminuição da viabilidade celular no córtex e estriado, e diminuição da atividade da catalase no estriado e hipocampo. Os resultados mostram que a presença de AG durante o desenvolvimento e crescimento ao longo de duas gerações é capaz de modificar parâmetros de comportamento e status oxidativo do cérebro. Tomados em conjunto, nossos dados suportam a ideia de que o consumo regular de uma dieta rica em ácidos graxos monoinsaturados (AGM) e AGPI, e particularmente pobre em alimentos processados, pode ajudar a prevenir o desenvolvimento de distúrbios emocionais, além de sugerir a influência nociva do consumo de gordura trans ao longo de gerações, a qual é capaz de aumentar parâmetros de emocionalidade e ansiedade após situações estressantes da vida cotidiana podendo desencadear condições neurológicas e neuropsiquiátricas mais graves.

Orientador: Luiz Jacintho Silva / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T10:32:11Z (GMT). No. of bitstreams: 1 Freitas_AndreRicardoRibas_M.pdf: 3288382 bytes, checksum: 1e4d10a420b3969b93fb46828328259d (MD5) Previous issue date: 2007 / Resumo: Os programas de controle da esquistossomose têm obtido relativo sucesso ao controlar a morbidade relacionada a altas cargas parasitárias desta doença, sem, no entanto, diminuir a área de transmissão no Brasil. Como a neuroesquistossomose medular á uma forma grave de esquistossomose não relacionada a altas cargas parasitárias existe risco teórico de ocorrer em áreas de baixa endemicidade. O objetivo deste estudo foi estudar a ocorrência da NE (neuroesquistossomose) medular em uma região de baixa endemicidade, região de Campinas, estado de São Paulo. Foi feito um estudo retrospectivo, descritivo de base hospitalar com busca ativa em múltiplas fontes de informação. Utilizou-se como base os dois maiores hospitais públicos da região de Campinas. Os pacientes com diagnóstico de NE medular tiveram seus diagnósticos ratificados por critérios padronizados e baseados em quadro clínico típico, comprovação da infecção por Schistosoma mansoni e exclusão de outras causas de mielopatia. Os pacientes foram classificados como autóctones, importados, sem informação e indeterminado. Após esta classificação os dados clínicos e epidemiológicos foram analisados. Foram identificados 27 pacientes com NE medular dos quais 19 (85,2%) homens e 4 (14,8%) mulheres, as idades no momento do diagnóstico foram de 13 a 57 anos (média=31,2; desvio padrão=12,8 e mediana=29). Os pacientes foram classificados quanto ao local provável de infecção da seguinte forma: 14(51,9%) autóctones, 11(40,7%) importados e 2(7,4%) sem informações, não houve paciente classificado como indeterminado. Todos os pacientes importados se infectaram em municípios de áreas de alta endemicidade. A clínica deste grupo de pacientes não foi diferente do encontrado na literatura, nem foi diferente quando comparados os pacientes autóctones com os importados. Houve uma demora média de 70,6 dias (mediana=19; dp=166,9) entre a primeira consulta e o diagnóstico. A demora foi em média 88,1 dias maior entre os pacientes autóctones (média=112 dias; mediana=26; dp=224,3) do que entre os importados (média=23,9 dias; mediana=9; dp=42,7) e esta diferença foi estatisticamente significativa p=0,0247. A sensibilidade da sorologia foi de 87,5%, da imunologia de LCR 93,8% e dos exames parasitológicos foi de 40,0%. Apenas 4 (14,8%) tiveram evolução com melhora completa, 6 (22,2%) apresentaram melhora sem limitações, 13 (48,1%) apresentaram melhora com limitações e 4 (14,8%) não apresentaram melhora alguma. Apenas 11 pacientes (41%) com NE medular incluídos neste estudo estavam notificados à vigilância epidemiológica e a informação de que estes pacientes tinham quadros neurológicos não constavam no banco de informações do SINAN. Concluiu-se que a NE medular ocorre mesmo em áreas de baixa endemicidade e nestas áreas existe uma demora muito grande no diagnóstico, principalmente entre os pacientes autóctones. O exame de fezes não se mostrou sensível para diagnóstico e rastreamento de pacientes vulneráveis a NE medular por se tratarem de pacientes com baixas cargas parasitárias. Portanto métodos diagnósticos mais sensíveis deveriam ser utilizados pelos programas de controle de esquistossomose / Abstract: Programs for schistosomiasis control have enjoyed relative success in controlling death associated to high parasitary loads for this illness, without, however, decreasing the area of transmission in Brazil. Since spinal neuroschistosomiasis is a grave form of neuroschistosomiasis unrelated to high parasitary loads, there is a theoretical risk of its occurrence even when not in a particularly endemic area. The goal of this study was to study the occurrence of spinal NE (neuroschistosomiasis) in a non-endemic area, the region of Campinas, in the Sate of São Paulo. A retrospective, descriptive, hospital-based study was carried, with information actively sought after from various sources of information. The two largest public hospitals in the region of Campinas were used as bases. The patients diagnosed with spinal NE had their diagnoses ratified according to standard criteria and based on typical clinical status, proof of infection by Schistosoma mansoni and the exclusion of other causes for myelopathy. Patients were classified as autochthonous, imported, without information and undetermined. After this classification, the clinical and epidemiological data were analyzed. A total of 27 patients with spinal NE were identified, of which 19 (85.2%) were men and 4 (14.8%) women. The ages on diagnosis ranged from 13 to 57 (average=31.2; standard deviation=12.8 and median=29). The patients were classified as to their probable location of infection the following way: 14(51.9%) autochthonous, 11(40.7%) imported and 2(7.4%) without information. No patients were deemed undetermined. All imported patients were infected in municipalities located in highly endemic areas. Clinical evaluation of this group of patients was no different from that found in the literature, nor was it different when autochthonous patients were compared to imported patients. There was an average period of 70.6 days (median=19; sd=166.9) between the first consultation and diagnosis. The period was on average 88.1 days longer for autochthonous patients (average=112 days; median=26; sd=224.3) than for imported patients (average=23.9 days; median=9; sd=42.7) and this difference was statistically significant p=0.0247. Sensitivity of the serology was 87.5%, LCR immunology 93.8% and for parasitological exams it was 40.0%. Only 4 (14.8%) had evolution with complete recovery, 6 (22.2%) presented improvement without limitations, 13 (48.1%) presented improvement with limitations and 4 (14.8%) did not present improvement. Only 11 patients (41%) with spinal NE included in the study had been notified to epidemiological surveillance and the information that these patients had neurological patterns of symptoms was not present in the SINAN data base. It can be concluded that spinal NE occurs even in non-endemic areas and that diagnosis in such locations can take excessively long, especially for autochthonous patients. Feces exams were not shown to be sensitive for diagnosis and tracing of patients vulnerable to spinal NE since such patients presented low parasitary loads. Therefore more sensitive means of diagnosis should be utilized by schistosomiasis control programs / Mestrado / Ciencias Biomedicas / Mestre em Clinica Medica