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This dissertation studies two problems related to geometric representation of neuroanatomical data: (i) spatial representation and organization of individual neurons, and (ii) reconstruction of three-dimensional neuroanatomical regions from sparse two-dimensional drawings. This work has been motivated by nearby development of new technology, Knife-Edge Scanning Microscopy (KESM), that images a whole mouse brain at cellular level in less than a month. A method is introduced to represent neuronal data observed in the mammalian brain at the cellular level using geometric primitives and spatial indexing. A data representation scheme is defined that captures the geometry of individual neurons using traditional geometric primitives, points and cross-sectional areas along a trajectory. This representation captures inferred synapses as directed links between primitives and spatially indexes observed neurons based on the locations of their cell bodies. This method provides a set of rules for acquisition, representation, and indexing of KESMgenerated data. Neuroanatomical data observed at the gross level provides the underlying regional framework for neuronal circuits. Accumulated expert knowledge on neuroanatomical organization is usually given as a series of sparse two-dimensional contours. A data structure and an algorithm are described to reconstruct separating surfaces among multiple regions from these sparse cross-sectional contours. A topology graph is defined for each region that describes the topological skeleton of the region’s boundary surface and that shows between which contours the surface patches should be generated. A graph-directed triangulation algorithm is provided to reconstruct surface patches between contours. This graph-directed triangulation algorithm combined together with a piecewise parametric curve fitting technique ensures that abutting or shared surface patches are precisely coincident. This method overcomes limitations in i) traditional surfaces-from-contours algorithms that assume binary, not multiple, regionalization of space, and in ii) few existing separating surfaces algorithms that assume conversion of input into a regular volumetric grid, which is not possible with sparse inter-planar resolution.

Sympathetic catecholamines and co-transmitters released within the gastrointestinal (GI) tract provide dynamic regulation of gut motility, fluid secretion, blood flow and immune cell function. Pathological GI inflammation in patients with inflammatory bowel diseases (IBD) evokes functional and structural plasticity in sympathetic neurons that innervate the gut, which may contribute to symptom generation. The mechanisms responsible for aberrant sympathetic behaviour during colonic inflammation remain elusive, though evidence points to a role for mediators of the mucosal immune response. Interleukin (IL)-17 is the principal cytokine of the novel TH17 lineage of helper T cells. Based on mounting clinical, genetic and experimental evidence, IL-17 is thought to play a pivotal role in the immunopathogenesis of IBD. However, nothing is known of the contribution of IL-17 to sympathetic neuroplasticity during chronic inflammatory disease. We hypothesized that remodelling of postganglionic sympathetic axons occurs in response to exposure of axons to the inflamed colonic milieu and that IL-17 serves as the primary mediator of this neuroanatomical remodelling. An increase in tyrosine hydroxylase (TH) immunoreactivity, a marker of sympathetic axons, was observed in the muscularis externae and mucosae of colons from mice subjected to acute and chronic models of dextran sulphate sodium (DSS)-induced colitis. In parallel, we found markedly elevated levels of IL-17 in the serum and colonic tissues of mice with colitis. To investigate whether the colitis microenvironment promoted axonal growth, distal neurites of adult sympathetic neurons from the superior mesenteric ganglion (SMG) were incubated in supernatant collected from explant cultures of inflamed colon. Colitis supernatant enhanced neurite outgrowth from gut-projecting SMG neurons compared to supernatants from control colon. Importantly, this effect was abrogated following the addition of IL-17-neutralising antiserum to cultures. Moreover, IL-17 increased the morphological complexity of SMG neurites in vitro while none of the other inflammatory cytokines known to be elevated during IBD had a similar effect. These findings suggest a novel role for IL-17 as a mediator of sympathetic neuroanatomical plasticity during colonic inflammation. Whether this contributes to the functional deficits and chronic inflammatory response that occurs in the GI tract during IBD remains to be determined. / Thesis (Master, Physiology) -- Queen's University, 2011-08-10 09:40:13.514

This study investigated the associations between (1) handedness (demonstrated preference of one hand for the performance of most unimanual tasks) and neuroanatomical asymmetry (measurable differences in width between the cerebral hemispheres) and (2) familial history of handedness (the presence of a left-handed sibling or parent of a right-handed subject) as an intervening factor in the relation between handedness and neuroanatomical asymmetry. Width measurements of the brain were derived from computerized tomographic ( CT) films and grouped in to categories by hand preference (measured by the Edinburgh Handedness Inventory) and family history. The measurements of right (n=68), right with left-· handed relatives (n=24), and left-handed (n=16) groups were then compared by width and other transformations of the brain measurements. Subjects were adults of both sexes who had been referred for neurologic examination and were diagnosed as free of major distorting brain pathology. Hemispheric widths were compared by group, as ratios (left÷right) and as differences (left-right). Analysis of variance revealed significant differences between right-hemisphere widths at three percentages of brain length in the posterior occipital and temporal-parietal portion of the right hemisphere. The two right-handed groups had significantly smaller right-hemisphere measurements than the left group at 80% (p=.03), 75% (p= .012), and 60% (p= .029) of brain length. There were no significant left-hemisphere differences between the groups. In terms of ratios of sides and differences between sides in the same brain region, the left - handed group was different from the right-handed group at the p Handedness appears to be moderately associated with neuroanatomical asymmetry. The differences in sizes of brain structures and their relation to functionally lateralized abilities may shed light on the processes by which each hemisphere becomes specialized to perform specific tasks and other aspects of individual differences.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / A retrospective study including dogs with neurological disease was conducted at the Service of Neurology (SN) of the Veterinary Teaching Hospital, Universidade Federal de Santa Maria (UFSM) between 2006 and 2013, with the objective to identify and characterize the age, breed and sex, neurological diseases and classify them according to the anatomical region and DINAMIT-V acronym. Were evaluated 1.277 neurological records of dogs and obtained the information for inclusion in the study in 1.184 of them being the etiological diagnosis in 525 (44,4%) and presumptive in 659 dogs (55,6%). The most common breeds were dachshunds (27,5%), followed by mixed breed. The most common sites were the spinal cord between T3-L3 (40,9%) and thalamus-cortex (17,5%). Most dogs were diagnosed with degenerative disorders (49%), being disc disease intervertebral more observed, followed inflammatory/infectious disease (16,6%). It can be concluded that the higher prevalence of neurological disorders in dogs involve the spinal cord and thalamus-cortex, with the most frequent being degenerative and the data obtained may assist future studies associated with frequency and distribution of the main neurological diseases in dogs. / Foi realizado um estudo retrospectivo de cães atendidos no Serviço de Neurologia (SN) do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria (UFSM), entre 2006 e 2013, com o objetivo de identificar e caracterizar a idade, raça e sexo, as doenças neurológicas e classificá-las de acordo com a região anatômica e acrônimo DINAMIT-V. Foram avaliadas 1.277 fichas neurológicas de cães e obtidas as informações para inclusão no estudo em 1.184 delas, sendo o diagnóstico etiológico confirmado em 525 cães (44,4%) e presuntivo em 659 (55,6%). As raças mais frequentes foram dachshunds (29,2%), seguido das sem raça definida. Os locais mais comuns foram a medula espinhal entre T3-L3 (40,9%) e tálamo-córtex (17,5%). A maioria dos cães foram diagnosticados com doenças degenerativas (49%) , sendo a doença do disco intervertebral a mais observada, seguido das doenças inflamatórias/infecciosas (16,6%). Pode-se concluir que a maior prevalência das doenças neurológicas de cães envolvem a medula espinhal e tálamo-cortex, sendo as degenerativas as mais frequentes e os dados obtidos poderão auxiliar em futuros estudos sobre a frequência e distribuição das principais doenças neurológicas em cães.

Nos travaux sur 26 gènes de la famille des WDR a permis d’en identifier sept (Atg16l1, Coro1c, Dmxl2, Herc1, Kif21b, Wdr47, Wdr89) associés à des anomalies cérébrales majeures. Cette grande famille de protéines reste pourtant peu explorée quant à ses rôles dans le développement du système nerveux central. Nous avons choisi d’étudier WDR47, dont la fonction est totalement inconnue en dépit d’une très grande similarité structurale avec LIS1, protéine à l’origine de la lissencéphalie. En combinant trois modèles expérimentaux (souris, siRNA et levure), nous avons démontré que Wdr47 est essentiel pour la survie de l’organisme et est impliqué dans la coordination motrice et le maintien de l’homéostasie énergétique avec une origine probablement centrale. Au niveau cellulaire, Wdr47 assure un rôle clé dans la dynamique des microtubules et la stabilisation du cône de croissance au travers d’interaction protéiques avec Reelin et SCG10. En outre, Wdr47 est aussi impliqué dans la prolifération neuronale et la macroautophagie. Ces résultats ont permis d’établir un lien de causalité entre une duplication de 200 kb contenant Wdr47 et des troubles de coordination motrice et une obésité hyperphagique chez un jeune patient. / WD40-repeat (WDR) proteins are one of largest eukaryotic family, however little is known about their role in neurodevelopment. We investigated 26 WDR genes, and found 7 (Atg16l1, Coro1c, Dmxl2, Herc1, Kif21b, Wdr47, Wdr89) with a major impact in brain structure when inactivated in mice. We chose WDR47 for further investigation, as it is a completely unknown protein that shares striking domain similarity with LIS1. Using three independent model systems (mice, siRNA and yeast), we found an essential role of Wdr47 in survival, and key neuronal processes involving microtubule dynamics such as proliferation, autophagy and growth cone stabilization. Next we identified Reelin and superior cervical ganglion 10 (SCG10) as top interacting proteins of WDR47. Interestingly, a 200-kb duplication encompassing WDR47 was linked to poor coordination in one patient, recapitulating mouse behavioural anomalies. Together our data help unravel for the first time a key role of Wdr47 in brain.

Esta tese teve como objetivo apresentar o processo de construção, aplicação e avaliação de uma ferramenta para o ensino da neuroanatomia, acessível a partir de computadores pessoais, imersiva, interativa, foto-realística e que permita visão tridimensional e estereoscópica. Quarenta encéfalos frescos foram obtidos no Serviço de Verificação de Óbitos de São Paulo (SVO-SP) e submetidos às técnicas de fixação, conservação, injeção vascular, coloração de substância cinzenta, dissecação de fibras brancas, terebintina e clareamento ósseo, conforme sua finalidade, no laboratório de Técnica Cirúrgica e Cirurgia Experimental da Universidade de São Paulo (USP). Imagens das áreas de interesse foram capturadas utilizando-se uma plataforma giratória manual construída para este fim. As imagens foram processadas com softwares comercialmente disponíveis (Photoshop CS5; Stereo Photo Maker;VRWorx2.6 para Windows) em formato não linear, interativo, tridimensional e estereoscópico, e armazenadas em um banco de 5.337 imagens finais. O recurso didático foi aplicado a 84 graduandos do curso de medicina, divididos em três grupos: convencional (grupo1), interativo não estereoscópico (grupo2) e interativo estereoscópico (grupo3), cujas médias na avaliação do conhecimento prévio não diferiram estatisticamente entre si (P > 0,05). A ferramenta foi avaliada através de uma prova teórica e prática. Verificou-se que os Grupos 2 e 3 apresentaram as maiores médias e diferiram estatisticamente do Grupo 1 (P < 0,05); o Grupo 2 não diferiu estatisticamente do Grupo 3 (p > 0,05), mostrando resultado do treinamento semelhante na prova teórica. Observando-se os Tamanhos do Efeito, verificou-se que esses foram de grande magnitude, indicando uma efetividade do treinamento dos alunos. Os resultados da ANOVA mostraram que existe diferença significativa (P < 0,05) entre as médias dos grupos, e por meio do teste de Tukey observou-se que existe diferença estatística entre o Grupo 1 e os demais (P < 0,05). Na prova prática pode-se observar, que de modo semelhante à prova teórica, não houve diferença estatística entre os Grupos 2 e 3. Os autores concluem que o método apresentado propiciou ganho de conhecimento e rendimento pedagógico significativamente superior quando comparado com o tradicional / This thesis aims to show the process of the construction, implementation and evaluation of a tool for teaching neuroanatomy. The tool presented is accessible from personal computers, immersive, interactive, and allows photorealistic three-dimensional and stereoscopic vision. Forty fresh brains were obtained from the São Paulo Department of Death Records (SP-DDR- Serviço de Verificação de Óbitos de São Paulo (SVO-SP)) and subjected to fixation, conservation, vascular injection, staining of gray matter, white fiber dissection, turpentine and bleaching bone techniques, as needed, at the Surgical Technique and Experimental Surgery Laboratory, University of São Paulo (Laboratório de Técnica Cirúrgica e Cirurgia Experimental da Universidade de São Paulo- USP). Images of areas of interest were captured using a manual turntable built for this purpose. The images were processed with commercially available software (Photoshop CS5; Stereo Photo Maker; VRWorx2.6 for Windows) non-linear format, interactive, three-dimensional stereoscopic and stored in a database of 5337 final images. The teaching resource was applied to 84 undergraduate medical students, divided into three groups: conventional (group 1), interactive non-stereoscopic (group 2) and interactive stereoscopic (group 3). Averages on the assessment of prior knowledge did not differ significantly (P > 0.05) among groups. The tool was evaluated through a written theory test and a lab practical. Groups 2 and 3 showed the highest averages and differed significantly from Group 1 (P < 0.05), Group 2 did not differ statistically from Group 3 (p > 0.05), revealing a result of similar training on the written theory test. Observing the Effect Sizes, it was found that those were of great magnitude, indicating student training effectiveness. ANOVA results showed significant difference (P < 0.05) between group means, and the Tukey test showed statistical difference between Group 1 and the others (P < 0.05). On the lab pratical, it may be noted that similarly to the written theory test, no statistical difference between Groups 2 and 3 were found. The authors conclude that the tool presented provided a gain of knowledge for students and yielded significantly higher leaning when compared with traditional teaching resources

Esta tese teve como objetivo apresentar o processo de construção, aplicação e avaliação de uma ferramenta para o ensino da neuroanatomia, acessível a partir de computadores pessoais, imersiva, interativa, foto-realística e que permita visão tridimensional e estereoscópica. Quarenta encéfalos frescos foram obtidos no Serviço de Verificação de Óbitos de São Paulo (SVO-SP) e submetidos às técnicas de fixação, conservação, injeção vascular, coloração de substância cinzenta, dissecação de fibras brancas, terebintina e clareamento ósseo, conforme sua finalidade, no laboratório de Técnica Cirúrgica e Cirurgia Experimental da Universidade de São Paulo (USP). Imagens das áreas de interesse foram capturadas utilizando-se uma plataforma giratória manual construída para este fim. As imagens foram processadas com softwares comercialmente disponíveis (Photoshop CS5; Stereo Photo Maker;VRWorx2.6 para Windows) em formato não linear, interativo, tridimensional e estereoscópico, e armazenadas em um banco de 5.337 imagens finais. O recurso didático foi aplicado a 84 graduandos do curso de medicina, divididos em três grupos: convencional (grupo1), interativo não estereoscópico (grupo2) e interativo estereoscópico (grupo3), cujas médias na avaliação do conhecimento prévio não diferiram estatisticamente entre si (P > 0,05). A ferramenta foi avaliada através de uma prova teórica e prática. Verificou-se que os Grupos 2 e 3 apresentaram as maiores médias e diferiram estatisticamente do Grupo 1 (P < 0,05); o Grupo 2 não diferiu estatisticamente do Grupo 3 (p > 0,05), mostrando resultado do treinamento semelhante na prova teórica. Observando-se os Tamanhos do Efeito, verificou-se que esses foram de grande magnitude, indicando uma efetividade do treinamento dos alunos. Os resultados da ANOVA mostraram que existe diferença significativa (P < 0,05) entre as médias dos grupos, e por meio do teste de Tukey observou-se que existe diferença estatística entre o Grupo 1 e os demais (P < 0,05). Na prova prática pode-se observar, que de modo semelhante à prova teórica, não houve diferença estatística entre os Grupos 2 e 3. Os autores concluem que o método apresentado propiciou ganho de conhecimento e rendimento pedagógico significativamente superior quando comparado com o tradicional / This thesis aims to show the process of the construction, implementation and evaluation of a tool for teaching neuroanatomy. The tool presented is accessible from personal computers, immersive, interactive, and allows photorealistic three-dimensional and stereoscopic vision. Forty fresh brains were obtained from the São Paulo Department of Death Records (SP-DDR- Serviço de Verificação de Óbitos de São Paulo (SVO-SP)) and subjected to fixation, conservation, vascular injection, staining of gray matter, white fiber dissection, turpentine and bleaching bone techniques, as needed, at the Surgical Technique and Experimental Surgery Laboratory, University of São Paulo (Laboratório de Técnica Cirúrgica e Cirurgia Experimental da Universidade de São Paulo- USP). Images of areas of interest were captured using a manual turntable built for this purpose. The images were processed with commercially available software (Photoshop CS5; Stereo Photo Maker; VRWorx2.6 for Windows) non-linear format, interactive, three-dimensional stereoscopic and stored in a database of 5337 final images. The teaching resource was applied to 84 undergraduate medical students, divided into three groups: conventional (group 1), interactive non-stereoscopic (group 2) and interactive stereoscopic (group 3). Averages on the assessment of prior knowledge did not differ significantly (P > 0.05) among groups. The tool was evaluated through a written theory test and a lab practical. Groups 2 and 3 showed the highest averages and differed significantly from Group 1 (P < 0.05), Group 2 did not differ statistically from Group 3 (p > 0.05), revealing a result of similar training on the written theory test. Observing the Effect Sizes, it was found that those were of great magnitude, indicating student training effectiveness. ANOVA results showed significant difference (P < 0.05) between group means, and the Tukey test showed statistical difference between Group 1 and the others (P < 0.05). On the lab pratical, it may be noted that similarly to the written theory test, no statistical difference between Groups 2 and 3 were found. The authors conclude that the tool presented provided a gain of knowledge for students and yielded significantly higher leaning when compared with traditional teaching resources