A lesão do nervo periférico resulta em dor neuropática persistente ou crônica, caracterizada por dor espontânea em queimação, acompanhada de alodinia e hiperalgesia. A ocorrência de alterações patológicas no sistema nervoso periférico e na medula espinal contribui para o desenvolvimento da dor neuropática. Estas alterações incluem descargas ectópicas nas fibras nervosas periféricas lesadas, as quais mantêm os impulsos nervosos aferentes para o sistema nervoso central. Várias substâncias sintetizadas e/ou liberadas durante o processo inflamatório tais como cininas, neuropeptídeos, citocinas, óxido nítrico, entre outros, assim como as alterações morfofuncionais celulares, podem interferir com a atividade dessas fibras. Estas alterações na homeostasia do indivíduo podem implicar em uma perda da qualidade de vida do paciente. Portanto, tais informações são essenciais para o auxílio de uma terapia analgésica eficiente e/ou preventiva. Assim, o presente projeto tem como objetivo compreender melhor a participação das isoformas neuronal e induzível em modelo de dor neuropática induzida pela lesão constritiva crônica do nervo isquiático de ratos. Para tanto, foi avaliada a sensibilidade dolorosa dos animais utilizando inibidor seletivo para NOS neuronal (nNOS) e induzível (iNOS), antes e após os testes comportamentais. Avaliamos também a distribuição das isoenzimas da NOS, na medula espinal e gânglios da raiz posterior, pelo método de imuno-histoquímica. Ainda, separadamente, analisou-se a síntese de nNOS e iNOS, pelo método de Western blot, e a presença de óxido nítrico utilizando marcador fluorescente DAF-2 (DA). Tais investigações poderão contribuir fornecendo base científica para o desenvolvimento de novos medicamentos e por elucidar alguns dos mecanismos de ação do óxido nítrico, envolvidos na dor neuropática, que é de difícil tratamento e de grande relevância clínica. / The peripheral nerve injury results in persistent or chronic neuropathic pain characterized by spontaneous burning pain accompanied by allodynia and hyperalgesia. The occurrence of pathological changes in the peripheral nervous system and spinal cord contributes to the development of neuropathic pain. These changes include ectopic discharges in damaged peripheral nerve fibers, which maintain the afferent nerve impulses to the central nervous system. Many substances synthesized and / or released during inflammation such as neuropeptides, cytokines, nitric oxide, among others, as well as cellular morphofunctional changes, may interfere with the activity of those fibers. These changes in the homeostasis of the individual can result in a loss of quality of life of the patient. Therefore, such information is essential for an effective analgesic therapy and / or preventive. The aims of this project are to better understand the involvement of neuronal and inducible isoforms in a model of neuropathic pain induced by chronic constriction injury in sciatic nerve of rats. We evaluated the pain sensitivity of animals using a selective inhibitor for neuronal (nNOS) and inducible (iNOS) NOS. We also evaluate the distribution of NOS isoenzymes in the spinal cord and dorsal root ganglia, by the method of immunohistochemistry. Separately, we analyzed the synthesis of iNOS and nNOS by Western blot assay, and the presence of nitric oxide using fluorescent probe DAF-2 (DA). Such research could contribute to providing scientific basis for the development of new drugs and to elucidate some of the mechanisms of action of NOS involved in neuropathic pain.

Introdução: A paralisia facial periférica caracteriza-se pela interrupção, definitiva ou temporária, do funcionamento da musculatura facial. Decorre de lesão ou mau funcionamento das fibras do nervo facial. É uma enfermidade que causa enorme impacto estético e funcional. O topodiagnóstico e o tratamento da paralisia facial periférica pode requer abordagem médica e fonoaudiológica; ser exclusivamente medicamentoso ou associado à terapia de reabilitação, ou ainda, medicamentoso e cirúrgico, seguido da reabilitação da mímica facial. A via FCM tem sido usada para a descompressão do NF quando a audição precisa ser preservada. Esse acesso pode ser realizado de forma isolada, ou combinado à via transmastóidea. Objetivo: Descrever uma técnica inovadora para a descompressão do nervo facial via fossa craniana média que permite a exposição direta dos segmentos labiríntico e timpânico do nervo facial, com a preservação da função da orelha interna. Métodos: Vinte cabeças extraídas de cadáveres adultos de ambos os gêneros, sem sinais de malformação, traumatismo, doença ou manipulação cirúrgica prévia foram usados neste estudo. Os pontos de referência utilizados foram a artéria meníngea média, o nevo petroso superficial maior, a eminência arqueada, o seio petroso superior, e o plano meatal seguido no ápice petroso a partir da sua porção mais anterior e medial. Foi feita a dissecação do plano meatal, com visualização do meato acústico interno, seguido no ápice petroso a partir da sua porção mais anterior e medial até a região do gânglio geniculado. Foi aberto o tégmen timpânico e identificada a porção timpânica do nervo facial. A dissecação seguiu no sentido retrógrado da porção timpânica do nervo facial em direção ao gânglio geniculado, até a sua porção labiríntica. A aracnoide do meato acústico interno era aberta, e depois de identificado o nervo facial, a bainha deste nervo era aberta em extensão exposta. Resultados: As distâncias médias, entre o canal semicircular lateral e a porção média do cabo do martelo eram similares em ambos os lados (4,0mm±0,5mm). As distâncias médias, da porção timpânica do nervo facial até metade do cabo do martelo foram determinadas e resultaram em 2,0mm ± 0,44mm, e em 2,2mm ± 0,48mm para os lados direito e esquerdo, respectivamente. O segmento timpânico do nervo facial apresentou, em média, comprimento total de 11mm ± 0,67mm para o lado direito, e 11,5mm±0,60mm para o esquerdo. Os comprimentos longitudinais da janela óssea confeccionada no tégmen timpânico foram, em média, 16,8mm±1,67mm para o lado direito, e 16,8mm ± 1,20mm para o lado esquerdo. Já os comprimentos transversais da janela óssea confeccionada no tégmen timpânico foram, em média, 5,5mm ± 1,20mm e 5,0mm ± 1,75mm para os lados direito e esquerdo, respectivamente. O valor médio da área elíptica formada pelos comprimentos longitudinal e transversal da janela óssea confeccionada no tégmen timpânico foram 72,5mm2 ± 22,5mm2 à direita, e 65,9mm2 ± 30,3mm2 à esquerda. Conclusão: A técnica proposta pode ser utilizada para a cirurgia de descompressão do nervo facial via fossa craniana média, pois permite acesso aos segmentos timpânico, labiríntico e metal desse nervo, sem impor risco à audição. Pela possibilidade de acessar a porção timpânica do nervo, sem a necessidade da abertura da mastoide, o procedimento permite que se reduza o tempo cirúrgico e os riscos aos pacientes / Background: Peripheral facial palsy is characterized by the permanent or temporary interruption of the functioning of the facial muscles. The middle cranial fossa (MCF) approach has been used for the decompression of the facial nerve (FN) when hearing needs to be preserved. In this work, we describe an innovative technique for the decompression of the FN through the MCF approach that allows the direct exposure of the labyrinthine and entire tympanic segment of the FN, with the preservation of inner ear function. Methods: Twenty cadavers heads were used in this study. The reference landmarks used were the middle meningeal artery, the greater superficial petrosal nerve, the arcuate eminence, the inferior petrosal sinus and the meatal plane following the petrous apex from its most anterior and medial portion. Results: The tympanic segment of the FN presented, on average, a total length of 11 ± 0.67mm to the right, and 11.5 ± 0.60mm to the left. The longitudinal lengths of bone window in the tegmen tympani were 16.8±1.67mm to the right, and 16.8 ± 1.20mm to the left. The cross-sectional lengths of the bone window in the tegmen tympani were 5.5 ± 1.20mm and 5.0±1.75mm to the right and left sides, respectively. The average value of elliptical area formed by the longitudinal and transversal lengths of the bone window made in the tegmen tympani were 72.5 ± 22.5mm2 to the right, and 65.9 ± 30.3mm2 to the left. Conclusion: The proposed technique can be used for the surgical decompression of the tympanic, labyrinthine and meatal segments of the FN through the MCF, without imposing a risk to hearing, in addition to reducing the surgical time and the risk to patients

The preterm delivery (<37 weeks gestation) rates are generally 5-9% in Europe, 12-13% in the US, and each year about 13 millions preterm infants are born worldwide (MacDorman and Mathews, 2009; Slattery and Morrison, 2002). The early exposure to the extra-uterine environment increases the risks of perinatal brain injury, involving more often the white matter. The white matter injury is characterized by a potential subsequent occurrence of cognitive problems, of developmental delay and of major motor deficits (e.g. cerebral palsy). <p>The most widely used imaging technique for studying neonatal brain is cranial ultrasound that can be performed at bedside and detects major brain abnormalities (hemorrhage, infarctions, cysts, dilatation of the lateral ventricles). However, it has a poor sensitivity for non-cystic or diffuse white matter abnormalities (WMA), the most common form of white matter injury in preterm infants. In comparison to ultrasound, MR (magnetic resonance) imaging has been reported to be superior in detecting WMA and is considered as an essential modality for imaging the neonatal brain. The standard sequences (e.g. T1-, T2-weighted imaging) are routinely performed for assessing not only brain anatomy, but also for evaluating brain lesions. Nevertheless, ¡§conventional MR imaging¡¨ has been criticized because it is limited in qualitative assessment and it does not provide information on the extent of specific white matter pathways injuries. <p>Currently, diffusion tensor imaging (DTI) enables more detailed exploration of white matter microstructure. Furthermore, DTI is now the best in vivo technique capable of delineating white matter pathways and quantifying microstructural changes not visible on conventional MR imaging. Diffusion tensor tractography allows the reconstruction of the principal white matter fibers. Moreover, it also provides diffusion indices like fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (£f//), transverse diffusivity (£f¢r) that help assess the changes in fiber tracts, even before myelination becomes histologically evident. <p>Structural MR imaging studies performed in neonates are scarce. A number of essential questions are still under debate, concerning the normal white matter structure, as well as premature brain injury. First, left language lateralization and right handedness are complex phenomena incompletely understood and the question rises whether structural lateralization already exist in healthy preterm neonates at term-equivalent age. Second, it is of interest to know whether gender-related structural differences exist in healthy preterm neonates. Finally, in the assessment of preterm brain injury, the relationship between WMA on conventional imaging and altered diffusion indices in fiber tracts is still unclear. Therefore, the aims of the thesis were to investigate the brain structure in a population of preterm neonates at term-equivalent age by DTI and probabilistic tractography.<p>The first part of this thesis (Study I and Study II) was devoted to the study of white matter structural characteristics in healthy preterm neonates. Previous studies have shown that structural asymmetries in language and motor related fibers are present in adults and in infants (Dubois et al. 2009; Westerhausen et al. 2007). Our hypothesis was that these structural asymmetries are already present in preterm neonates at term-equivalent age. In Study I, DTI and probabilistic tractography were performed and we found volume and microstructural asymmetries in the language related parieto-temporal superior longitudinal fasciculi (SLF), in the motor related corticospinal tract (CST) and in the motor part of the superior thalamic radiation (STR) as well. In Study II, we found that compared to boys, girls have larger relative tract volumes and an advanced maturation in language and motor related fiber tracts. <p>The second part of this thesis (Study III) investigated whether WMA on conventional MR imaging are related to abnormalities within the fiber tract microstructures. WMA were classified as normal, mild, moderate and severe according to Woodward¡¦s classification (Woodward et al. 2006). Woodward and colleagues studied a large population (167 infants) of preterm infants at term equivalent age with MRI. They demonstrated that WMA were important predictors of neurological outcomes by comparing their results with the neurological outcomes of those infants at corrected age of two. We found that compared to neonates with no abnormalities, infants with mild abnormalities have significantly higher ƒÜ¢r in the right CST, the left anterior thalamic radiation (ATR), the left sensory STR and bilateral motor STR. Those findings might be related to injuries of premyelinating oligodendrocytes resulting in subsequent failure of both development and ensheathment of axons. Considering that those fiber tracts connect important cortical zones, microstructural changes in those fiber tracts might be responsible for the later neurodevelopment deficits in motor and cognitive functions. <p>We concluded that structural asymmetries and gender differences in motor and language related fibers are present in healthy preterm neonates at term-equivalent age well before the development of speech and hand preference. Structural asymmetries and gender differences have to be considered in neonatal white matter assessment. Finally, altered DTI indices are associated with WMA on conventional MR imaging in preterm neonates. Our results suggest that disrupted premyelination is the major correlate with WMA rather than axonal pathology. Non-invasive DTI and tractography constitute an additional tool for the assessment of white matter injuries, as it could provide more adequate diagnostic information on brain microstructure in preterm neonates at term-equivalent age. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

La locomotion est une composante fondamentale de la vie animale : elle permet l’accès continu aux ressources nécessaires à la survie ainsi que l’évitement de périls variés. Les milieux naturels comme anthropiques regorgent toutefois d’obstacles s’élevant contre notre progression. Pour l’humain et les autres mammifères terrestres naviguant principalement par la vision, le franchissement efficace de ces obstacles repose critiquement sur la capacité de modifier proactivement le positionnement et la trajectoire des pas en fonction des informations visuelles extraites durant leur approche. Au niveau du système nerveux, cette capacité implique un processus complexe où le traitement des signaux visuels reflétant les paramètres de l’obstacle spécifie un cours d’action sécurisant son franchissement, lequel est ultimement exécuté par des altérations précises à l’activité musculaire. Des études approfondies chez le chat, l’un des modèles animaux les plus développés et investigués vis-à-vis du contrôle locomoteur, ont présentement impliqué deux structures corticales dans ce processus. Le cortex pariétal postérieur contribuerait ainsi à déterminer la position relative de l’obstacle et le cortex moteur primaire serait central à l’exécution des modifications de la démarche. Cependant, notre compréhension du substrat neural impliqué dans la transformation sensorimotrice joignant ces deux étapes est extrêmement limitée. Plusieurs lignes d’évidences, particulièrement dérivées de travaux chez le primate investiguant le contrôle des mouvements volontaires du bras, pointent cependant vers une contribution potentiellement majeure du cortex prémoteur à cette fonction. Cette thèse entreprend de déterminer directement la contribution prémotrice aux modifications de la démarche. Deux études rapportent ainsi l’activité de neurones individuels enregistrés dans deux larges subdivisions du cortex prémoteur, les aires 6iffu et 4delta, chez le chat éveillé accomplissant librement une tâche de négociation d’obstacles sur tapis roulant. Ces études font état de changements d’activité distincts d’une subdivision à l’autre et corrélés à des aspects spécifiques de la tâche, incluant des changements préparatoires liés à l’approche finale de l’obstacle et d’autres liés à une ou plusieurs étapes des ajustements locomoteurs séquentiels entourant sa négociation. Une troisième étude investigue par microstimulation intracorticale la capacité des différentes subdivisions prémotrices du chat à modifier la démarche. Cette étude expose une variété de réponses électromyographiques complexes s’intégrant en phase avec la marche, où plusieurs subdivisions présentent des signatures distinctes d’effets multi-membres contrastant avec l’influence focale du cortex moteur primaire. Chacune de ces trois études est finalement complémentée d’investigations par traçage rétrograde de connexions anatomiques décisives à l’interprétation fonctionnelle des subdivisions investiguées. Ensemble, ces travaux soutiennent et précisent une contribution centrale du cortex prémoteur aux modifications de la démarche sous guidage visuel. D’une part, ils rapportent pour la première fois que l’activité neuronale de multiples subdivisions du cortex prémoteur reflète différentes étapes de la planification locomotrice stipulant les altérations à entreprendre à l’approche d’un obstacle et durant son franchissement. D’autre part, ils révèlent complémentairement que l’activation de ces subdivisions a le pouvoir d’influencer profondément la marche. Les données collectées soulignent finalement plusieurs points de comparaison entre les aires prémotrices du chat et du primate, suggérant un degré d’analogie fonctionnelle extensible à la locomotion humaine. / Locomotion is a fundamental component of animal life: it provides continuous access to the resources necessary for survival as well as the means to elude potential perils. However, both natural and built environments teem with obstacles impeding one’s progress. For humans and other terrestrial mammals navigating primarily through vision, efficiently negotiating these obstacles critically requires the capacity to proactively adapt the positioning and trajectory of each step on the basis of visual information extracted during their approach. In the nervous system, this capacity involves a complex process through which the integration of visual signals reflecting the parameters and location of an obstacle specifies a course of action to ensure its negotiation, Extensive studies in the cat, one of the most common models used to study the neural mechanisms involved in the control of locomotion, have currently implicated two cortical structures to this process. The posterior parietal cortex is suggested to contribute to the determination of the obstacle’s relative position (with respect to the body) while the primary motor cortex is central to the execution of the gait modifications. However, our comprehension of the neural substrate implicated in the sensorimotor transformation linking these defined stages is extremely limited. Several lines of evidence, predominantly derived from work in the primate investigating the voluntary control of arm movements, nonetheless point towards a potentially major contribution of the premotor cortex to this function. This thesis sets out to directly determine the premotor contribution to the control of gait modifications. Two studies report the activity of individual neurons recorded in two large subdivisions of premotor cortex, areas 6iffu and 4delta, in awake cats freely performing an obstacle negotiation task on treadmill. These studies describe distinct changes in activity across subdivisions that correlate with specific aspects of the task, including preparatory changes related to the final approach of the obstacle and others related to one or more stages of the sequential locomotor adjustments surrounding its negotiation. A third study used intracortical microstimulation to investigate the capacity of different premotor subdivisions of the cat to modify gait. This study reveals a variety of complex electromyographic responses that are integrated into the gait cycle. Moreover, several subdivisions show distinct signatures of multi-limb effects that contrast with the focal influence of the primary motor cortex. Each of these three studies is finally complemented by retrograde tracing investigations of anatomical connections critical to the functional interpretation of the subdivisions examined. Together, these studies support and clarify a central contribution of the premotor cortex to the modification of gait under visual guidance. We report for the first time that the neural activity of multiple subdivisions of the premotor cortex reflects different stages of the locomotor plan specifying the gait alterations to perform during the approach and crossing of an obstacle. In addition, we reveal that activation of these subdivisions has the power to profoundly influence walking. The data collected finally highlight several points of comparison between the premotor areas of the cat and the primate, suggesting a degree of functional analogy extensible to human locomotion.

Il est maintenant bien établi que le cerveau humain est doté d’un système de neurones qui s’active tant à la perception qu’à l’exécution d’une action. Les neurones miroirs, ainsi que le système qu’ils forment avec des structures adjacentes appelées système neurones miroirs (SNM), ont été relié à la compréhension d’action et pourrait être impliqué dans les fonctions sociales de haut niveau tel que l’empathie et l’imitation. Dans la foulée spéculative reliant le SNM à la sphère sociale, le dysfonctionnement de ce système a rapidement gagné intérêt dans la genèse des anomalies du domaine social chez les personnes présentant le Trouble du spectre de l’autisme (TSA). Néanmoins, l’hypothèse voulant que le dysfonctionnement social des TSA repose sur une atteinte du SNM est controversée. En effet, les études soutenant cette hypothèse nécessitent des fonctions cognitives et sociales qui peuvent contribuer à l’obtention de résultats atypiques, telles que la compréhension des consignes, l’attention sur des stimuli sociaux ou la réalisation d’acte moteur. Récemment, un protocole auditif de négativité de discordance (MMN) utilisant des stimuli reliés à l’action humaine a été utilisé pour mesurer l’activité du SNM. Cette technique semble prometteuse dans la mesure où elle ne nécessite pas de capacités attentionnelles ou langagières, elle est brève et demande un montage minimal d’électrodes. Le premier article avait comme objectif principal de mesurer la validité de convergence du protocole MMN relié à l’action avec celui du rythme mu, le protocole le plus utilisé pour enregistrer l’activité miroir à l’aide de l’électroencéphalographie (EEG). Les modes de stimulation ont été délivrées en bloc successif à un groupe de 12 adultes en santé. Alors que les deux techniques ont modulé efficacement les régions fronto-centrales et centrales respectivement, mais ne sont pas corrélées, nous avons conclu qu’il est possible 2 qu’elles mesurent des aspects différents du SNM. Le deuxième article avait comme objectif principal de mesurer l’activité du SNM à l’aide du protocole MMN relié à l’action chez 10 enfants présentant un TSA ainsi que chez 12 enfants neurotypiques dans la même tranche d’âge (5-7ans). Chez les enfants TSA, nous avons montré un patron de latence inversée, comparativement aux enfants du groupe contrôle; ils traitaient plus rapidement les sons contrôles que les sons reliés à l’action humaine, alors que la tendance inverse était observée chez les contrôles. De plus, bien que les deux groupes différaient quant aux sons d’action, ils ne différaient pas quant aux sons contrôles. Quant à l’amplitude, les enfants TSA se distinguaient du groupe contrôle par une amplitude restreinte du son d’action provenant de la bouche. Par ailleurs, les mesures neurophysiologiques et neuropsychologiques n’étaient pas corrélées. En sommes, basé sur la prémisse que ce protocole MMN pourrait mesurer l’activité du SNM, cette thèse a comme but d’améliorer les connaissances quant à son utilisation chez l’adulte et l’enfant neurotypique ainsi que chez l’enfant TSA. Celui-ci pourrait ultimement être utilisé comme un biomarqueur potentiel du TSA. / Mirror-neuron system (NMS) has been suggested to underlie action understanding, which is believed to be involved in higher social functions such as empathy and imitation. Numerous studies have also provided indirect evidence supporting the existence of a MNS in the human brain using functional magnetic resonance imaging, transcranial magnetic stimulation, magnetoenceophalography and electroencephalography (EEG). As evidence relating MNS function with social cognition accumulated, its dysfunction was proposed to underlie social impairments in Autism Spectrum Disorder (ASD). Although some studies have reported structural and/or functional data supporting this hypothesis, it remains controversial. Indeed, the techniques used to probe MNS activity often require the participant to understand the task, display sustained attention and present spared visual cognitive functions, which could be altered in ASD population. This, in turn, could partly explain differences in MNS activity found between invididuals with ASD and neurotypical participants. The auditory mismatch negativity (MMN) protocol has recently been proposed as a viable tool to assess MNS activity using action-related sounds. This relatively short oddball paradigm does not require visual, attentional or language skills and can be performed with minimal electrode installation (minimal use of 4 electrodes). This action-related MMN may therefore be well-suited to investigate MNS function in very young children or populations with mental disabilities, such as ASD. The first article of this thesis assessed the convergent validity of the action-related MMN protocol with a mu rhythm suppression paradigm, which is the most commonly used EEG measure of MNS activity. To do so, both protocols were consecutively administered in healthy adults in the same experimental session. While both techniques successfully 4 modulated the fronto-central and central brain regions using action-related stimuli, they did not correlate significantly. This suggests that the two techniques may not probe the same aspects of MNS function. The second article aimed at investigating MNS activity in children with ASD using the action-related MMN protocol. Data were compared to age-matched typically developing children. We show that children with ASD present an opposite pattern to that of control children : whereas MMN latencies are shorter for action-related sounds compared to control sounds in neurotypical children, the opposite pattern is observed in children with ASD. Furthermore, although the two groups present different response patterns with regards to action-related sounds, they repond similarly to control sounds. For amplitude measurements, children with ASD display reduced amplitude to action-related sounds produced by the mouth compared to neurotypical children. In summary, this thesis aimed at determining whether and action-related MMN protocol could be used to measure MNS activity in neurotypical adults and children, as well as in ASD children. The action-related MMN could potentially be used as a biological biomarker of ASD pending further studies.

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

Introdução: A técnica clássica para o implante coclear é realizada por meio de mastoidectomia seguida de timpanotomia posterior. O acesso pela fossa craniana média provou ser uma alternativa valiosa, embora seja usada para o implante coclear, ainda sem normatização. Objetivo: Descrever um novo acesso pela fossa craniana média que expõe o giro basal da cóclea para o implante coclear. Métodos: Estudo anatômico de ossos temporais. Foram dissecados 50 ossos temporais. A cocleostomia foi realizada mediante um acesso via fossa craniana média, na porção mais superficial do giro basal da cóclea, usando o plano meatal e seio petroso superior como as principais referências anatômicas. Foi determinada a distância entre os pontos de referência, o ângulo entre o plano meatal e a cocleostomia, e a distância entre esta estrutura e a janela redonda. Foi realizada tomografia computadorizada em 5 dos ossos temporais utilizados neste estudo. Resultados: Em todos os 50 ossos temporais, apenas a porção mais superficial do giro basal da cóclea foi aberta e tanto as escalas timpânica como a vestibular foram visualizadas. As distâncias médias ± DP, menores e maiores, entre a cocleostomia e o plano meatal foram estimadas em 2,48±0,88mm e 3,11±0,86mm, respectivamente. A distância média da cocleostomia até a janela redonda foi de 8,38±1,96mm, e daquela até o seio petroso superior 9,19±1,59mm. As distâncias médias, menores e maiores, entre a cocleostomia e o eixo longo do plano meatal a partir da sua porção mais proximal foram estimadas em 6,63±1,38mm e 8,2±1,43mm, respectivamente. O valor médio do ângulo entre a cocleostomia e o plano meatal foi igual a 22,54±7,400. As tomografias computadorizadas demonstraram a inserção do feixe de eletrodos por meio do giro basal da cóclea até o seu ápice em todas as peças submetidas a este exame. Conclusão: A técnica proposta para identificar o giro basal da cóclea é simples e confiável. Igualmente, permite a visualização da escala timpânica e a inserção do feixe de eletrodos do implante coclear através desta câmara / Introduction: The classic technique for cochlear implantation uses mastoidectomy followed by posterior tympanotomy. The middle cranial fossa approach has proved to be a valuable alternative for cochlear implantation, although the standardization of this technique is still needed. Objectives: To describe a novel approach through the middle cranial fossa for exposing the cochlear basal turn for cochlear implantation. Materials And Methods: Anatomical temporal bone study. Fifty temporal bones were dissected. A cochleostomy was performed via a middle fossa approach on the most superficial part of the cochlear basal turn, using the meatal plane and superior petrous sinus as the main landmarks. The distance between the landmarks, the angle between the cochleostomy and the meatal plane, and the distance between this structure and the round window were measured. A computed tomography was performed on 5 of the studied temporal bones. Results: In all 50 temporal bones, only the superficial portion of the cochlear basal turn was uncovered. The cochlear exposure allowed both the scala tympani and vestibule to be exposed. The mean ± SD minor and major distances between the cochleostomy and the meatal plane were estimated to be 2.48±0.88mm and 3.11±0.86mm, respectively. The mean distance from the cochleostomy to the round window was 8.38±1.96mm, and that to the superior petrosal sinus was 9.19±1.59mm. The mean minor and major distances between the cochleostomy and the long axis of the meatal plane from its most proximal portion were estimated to be 6.63±1.38mm and 8.29±1.43mm, respectively. The mean angle between the cochleostomy and the meatal plane was 22.54±7.400. The computed tomography of all 5 temporal bones demonstrated the insertion of the implant array from the cochlear basal turn towards its apex. Conclusion: The proposed technique for identifying the cochlear basal turn is simple and trustworthy. Additionally, it enables visualization of the scala tympani, facilitating the insertion of the cochlear implant array through this chamber

Introdução: A técnica clássica para o implante coclear é realizada por meio de mastoidectomia seguida de timpanotomia posterior. O acesso pela fossa craniana média provou ser uma alternativa valiosa, embora seja usada para o implante coclear, ainda sem normatização. Objetivo: Descrever um novo acesso pela fossa craniana média que expõe o giro basal da cóclea para o implante coclear. Métodos: Estudo anatômico de ossos temporais. Foram dissecados 50 ossos temporais. A cocleostomia foi realizada mediante um acesso via fossa craniana média, na porção mais superficial do giro basal da cóclea, usando o plano meatal e seio petroso superior como as principais referências anatômicas. Foi determinada a distância entre os pontos de referência, o ângulo entre o plano meatal e a cocleostomia, e a distância entre esta estrutura e a janela redonda. Foi realizada tomografia computadorizada em 5 dos ossos temporais utilizados neste estudo. Resultados: Em todos os 50 ossos temporais, apenas a porção mais superficial do giro basal da cóclea foi aberta e tanto as escalas timpânica como a vestibular foram visualizadas. As distâncias médias ± DP, menores e maiores, entre a cocleostomia e o plano meatal foram estimadas em 2,48±0,88mm e 3,11±0,86mm, respectivamente. A distância média da cocleostomia até a janela redonda foi de 8,38±1,96mm, e daquela até o seio petroso superior 9,19±1,59mm. As distâncias médias, menores e maiores, entre a cocleostomia e o eixo longo do plano meatal a partir da sua porção mais proximal foram estimadas em 6,63±1,38mm e 8,2±1,43mm, respectivamente. O valor médio do ângulo entre a cocleostomia e o plano meatal foi igual a 22,54±7,400. As tomografias computadorizadas demonstraram a inserção do feixe de eletrodos por meio do giro basal da cóclea até o seu ápice em todas as peças submetidas a este exame. Conclusão: A técnica proposta para identificar o giro basal da cóclea é simples e confiável. Igualmente, permite a visualização da escala timpânica e a inserção do feixe de eletrodos do implante coclear através desta câmara / Introduction: The classic technique for cochlear implantation uses mastoidectomy followed by posterior tympanotomy. The middle cranial fossa approach has proved to be a valuable alternative for cochlear implantation, although the standardization of this technique is still needed. Objectives: To describe a novel approach through the middle cranial fossa for exposing the cochlear basal turn for cochlear implantation. Materials And Methods: Anatomical temporal bone study. Fifty temporal bones were dissected. A cochleostomy was performed via a middle fossa approach on the most superficial part of the cochlear basal turn, using the meatal plane and superior petrous sinus as the main landmarks. The distance between the landmarks, the angle between the cochleostomy and the meatal plane, and the distance between this structure and the round window were measured. A computed tomography was performed on 5 of the studied temporal bones. Results: In all 50 temporal bones, only the superficial portion of the cochlear basal turn was uncovered. The cochlear exposure allowed both the scala tympani and vestibule to be exposed. The mean ± SD minor and major distances between the cochleostomy and the meatal plane were estimated to be 2.48±0.88mm and 3.11±0.86mm, respectively. The mean distance from the cochleostomy to the round window was 8.38±1.96mm, and that to the superior petrosal sinus was 9.19±1.59mm. The mean minor and major distances between the cochleostomy and the long axis of the meatal plane from its most proximal portion were estimated to be 6.63±1.38mm and 8.29±1.43mm, respectively. The mean angle between the cochleostomy and the meatal plane was 22.54±7.400. The computed tomography of all 5 temporal bones demonstrated the insertion of the implant array from the cochlear basal turn towards its apex. Conclusion: The proposed technique for identifying the cochlear basal turn is simple and trustworthy. Additionally, it enables visualization of the scala tympani, facilitating the insertion of the cochlear implant array through this chamber