Objectifs : Le bruxisme survenant au cours du sommeil est un trouble du mouvement caractérisé par du grincement de dents et l’activité rythmique des muscles masticateurs (ARMM). Le bruxisme/ARMM est souvent associé à des mouvements du corps et des à éveils corticaux. Une séquence d’activation précède le ARMM/bruxisme. Ces événements incluent une augmentation des variables suivants : l’activité sympathique (-4 minutes), les activités encéphalographique (-4 second), le fréquence cardiaque, l’amplitude de la respiration (-1 second) et l’activité des muscle suprahyoïdiens (-0.8 second). La présente étude a examiné l’association entre le bruxisme et les changements de la pression artérielle. Méthodes: Dix sujets avec le bruxisme (5 hommes, 5 femmes, âge moyen = 26 ± 1,8) ont complétés 3 nuits de polysomnographie qui comprenait l'enregistrement non invasive de la pression artérielle. La première nuit a servi de dépistage et d’habituation au laboratoire. L'analyse a été réalisée sur les deuxièmes et troisièmes nuits enregistrements. Seuls les épisodes de bruxisme isolés survenant au cours du stade 2 du sommeil ont été utilisés pour l’analyse, pour un total de 65 épisodes. Les mesures des pressions systolique et diastolique ont été prises 20 battements avant et 23 battements après l'apparition de chaque épisode bruxisme lors du sommeil. Les épisodes de bruxisme ont été classés comme suit: 1) bruxisme avec éveil cortical; 2) bruxisme avec mouvement du corps (MC), 3) bruxisme avec éveil cortical et MC. Une quatrième catégorie, bruxisme seul, a également été analysée, mais utilisée comme donnée préliminaire puisque la catégorie se composait de seulement 4 épisodes de bruxisme. Résultats: Les deux pressions systolique et diastolique ont augmenté avec les épisodes de bruxisme. Cette augmentation a été statistiquement significative pour la pression systolique et diastolique pour les épisodes de bruxisme avec éveil cortical et/ou MC (p ≤ 0,05). L’augmentation moyenne de la pression (systolique / diastolique ± SE) a été : 28,4 ± 2,4/13,2 ± 1,5 mm Hg pour le bruxisme avec éveil cortical; 30,7 ± 1,6/19.4 ± 2.3 mm Hg pour bruxisme avec MC; 26.4 ± 2,8 / 14,6 ± 2.0mm Hg pour bruxisme avec éveil cortical et MC; 22,9 ± 5,2/12,4 ± 3,3mm Hg pour les épisodes de bruxisme seuls. Conclusion: Le bruxisme du sommeil est associé à des hausses de la pression artérielle pendant le sommeil. Cette hausse est supérieure dans les épisodes de bruxisme associés à un éveil cortical et / ou MC, qui sont souvent associés avec les événements bruxisme. Ces résultats sont en accord avec nos observations antérieures, où le bruxisme est précédé par une augmentation de l'activité sympathique et de la tachycardie sinusale. / Objectives: Sleep Bruxism (SB) is a movement disorder identified by tooth grinding and rhythmic masticatory muscle activity (RMMA). It is often associated with body movements and sleep arousals. Increases in autonomic sympathetic activities that characterize sleep arousal precede SB. These events include an augmentation of the following variables: sympathetic cardiac activity (-4 minutes), electroencephalography frequencies (-4 seconds), heart rate and respiratory amplitude (-1 seconds), and suprahyoid muscle activity (-0.8 seconds). This study examined whether these sympathetic activities are associated with significant changes in arterial blood pressure (BP). Methods: Ten subjects with SB (5 male; 5 female; mean age ± standard error = 26 ± 1.8) underwent 3 nights of full polysomnography that included non-invasive beat to beat BP recording. The first night served as a screening and habituation night. Analysis was performed on second and third night recordings. Overall analysis was based on single SB episodes occurring in stage 2 sleep only, for a total of 65 episodes. Systolic and diastolic BP measurements were taken from a window of 20 beats before and 23 beats after onset of each SB episode. SB episodes were categorized as: 1) SB + cortical arousal; 2) SB + body movement (BM); 3) SB + cortical arousal + BM. A fourth category, SB alone, was also analysed but used as preliminary data since the category consisted of only 4 episodes. Results: Both systolic and diastolic BP increased with SB episodes. This increase was significant for both systolic and diastolic BP for SB events with cortical arousal and/or BM (p≤0.05). The average BP surges (systolic/diastolic ± SE) were: 28.4 ± 2.4/13.2 ± 1.5mm Hg for SB + cortical arousal; 30.7 ± 1.6/19.4 ± 2.3mm Hg for SB + BM; 26.5 ± 2.8/14.6 ± 2.0mm Hg for SB + cortical arousal + BM; 22.9 ± 5.2/12.4 ± 3.3mm Hg for SB episodes occurring alone. Conclusion: Sleep bruxism is associated with blood pressure fluctuations during sleep. This BP surge is greater in SB episodes associated with cortical arousal and/or BM, which often co-occur with SB events. These results are congruent with our previous observations, where SB is preceded by a rise in sympathetic activity and sinus tachycardia.

La migration radiaire est un des processus clefs de la corticogenèse menant à l’établissement d’un cortex en six couches chez les mammifères. La compréhension de ce mécanisme complexe est nécessaire à une meilleure appréhension du développement cortical. Dans ce travail de thèse, j’ai étudié la migration des neurones pyramidaux du cortex sous deux angles distincts. La 1ère partie se place d’un point de vue développemental en appréciant comment le positionnement laminaire résultant d’une migration normale ou anormale affecte la maturation neuronale. La 2nde partie se concentre sur une pathologie migratoire, l’hétérotopie en bande sous-corticale, et les altérations cognitives parfois associées à cette malformation. Pour ces deux projets, la migration neuronale a été altérée chez le rat par knockdown (KD) in utero de la doublecortine (Dcx), un effecteur majeur de la migration. Les neurones positionnés anormalement présentent une orientation incorrecte, un arbre dendritique moins développé, une spinogenère réduite et une altération morpho-fonctionnelle de la synaptogenèse glutamatergique. De plus, notre étude a mis en évidence l’implication de Dcx dans la dendritogenèse et la régulation fine des synapses glutamatergiques in vivo. Enfin, nous avons utilisé les rats Dcx-KD comme modèle d’hétérotopie en bande afin d’étudier comment un déficit de migration neuronale impacte le fonctionnement du cortex. La caractérisation comportementale, réalisée à l’aide d’une large gamme de tests, n’a pas mis en évidence de déficits majeurs des capacités motrices, somatosensorielles ou cognitives chez ces animaux. / Radial migration is one of the key processes leading to the formation of a six-layered cortex in mammals. Understanding this mechanism is necessary to get a better grasp of cortical development. During my PhD, I studied neuronal migration of pyramidal neurons from two different points of views. The 1st part is related to fundamental biology and assesses how laminar misplacement resulting from migration failure influences neuronal maturation. The 2nd one focuses on pathology by investigating a migration disorder, subcortical band heterotopia, and associated cognitive deficits. For both projects, neuronal migration was impaired in rat through in utero knockdown (KD) of doublecortin (Dcx), a major effector of cortical migration. Misplaced neurons display an abnormal orientation, a simplified dendritic arbor, a decreased spinogenesis and morpho-functional alterations of glutamatergic synaptogenesis. Moreover, our study shows that Dcx plays a role in dendritogenesis, in shaping spine morphology and in fine-tuning glutamatergic synaptogenesis. Finally, we used Dcx-KD rats as an animal model of subcortical band heterotopia to assess how migration failure would impact cortical functions. The behavioral characterization carried out through a wide range of tests did not bring to light any major shortcoming regarding motor, somatosensory or cognitive abilities in these animals. Therefore, although Dcx-KD rats display a SBH and develop spontaneous seizures, it does not seem to recapitulate cognitive deficits found in patients.

Le néocortex est une région du cerveau qui traite toutes les entrées sensorielles et créé des réponses comportementales. Il est subdivisé en zones fonctionnelles, chacune ayant une cytoarchitecture, un motif d’expression génique et un profil de connectivité spécifiques. L'organisation en zones est pré-modelée par des gènes organisateurs, et ensuite affinée par l’activité sensorielle. Dans cette étude, j'ai étudié d'abord si ce pré-modelage est établi dans les progéniteurs et/ou les cellules post-mitotiques, et si l'activité neuronale spontanée est nécessaire pour l’établissement de la connectivité correcte entre néocortex et thalamus, station relais principale des données sensorielles. Avec l'aide d'une série de souris transgéniques, j’ai montré que la fonction du gène organisateur COUP-TFI est suffisante et nécessaire pour organiser l'identité sensorielle dans les cellules post-mitotiques, et que COUP-TFI régule l'activité intrinsèque des neurones corticaux, influençant la bonne intégration des entrées thalamiques dans le cortex somatosensoriel. J’ai montré que COUP-TFI contrôle directement l'expression du gène Egr1, qui dépend fortement de l'activité neuronale. COUP-TFI et Egr1 agissent sur l'acquisition de la morphologie des cellules étoilées dans les neurones de la couche 4, cibles principales des axones thalamiques et trait typique des zones somatosensoriels primaires. En conclusion, ce travail montre que le pré-modelage cortical dépend primordialement d’un programme génétique établi dans les cellules post-mitotiques et que l'activité intrinsèque et les propriétés génétiques agissent ensemble pour façonner l'organisation des premiers circuits dans le néocortex. / The neocortex is a region of the brain that processes all sensory inputs creating appropriate behavioral responses. It is subdivided into functional areas, each with a specific cytoarchitecture, gene expression pattern and connectivity profile. The organization into areas is pre-patterned by the action of areal patterning genes, and subsequently refined by sensory evoked activity. In this study, I have first investigated whether early areal patterning is committed in progenitor and/or post-mitotic cells, and then assessed whether spontaneous neuronal activity is required in establishing correct connectivity between the neocortex and the thalamus, the principal relay station of peripheral sensory inputs. With the help of a series of transgenic mice, my work showed that the function of the areal patterning gene COUP-TFI is sufficient and necessary to organize sensory identity in post-mitotic cells, and that COUP-TFI regulates intrinsic activity properties of cortical neurons, and thus proper integration of thalamic inputs into the somatosensory cortex. In particular, I found that COUP-TFI directly controls the expression of the immediate early gene Egr1, which expression levels strongly depend on neuronal activity. Both COUP-TFI and Egr1 act on the acquisition of the stellate cell morphology of layer 4 neurons, the main targets of thalamic axons and a typical trait of primary somatosensory areas. In conclusion, this work demonstrates that cortical area patterning primordially depends on a genetic program established in post-mitotic cells and that intrinsic genetic and activity properties act together to shape the organization of early circuits in the neocortex.

L’os est un matériau dont les propriétés évoluent tout au long de la vie en fonction des contraintes environnementales. Aujourd’hui, les modalités d’imagerie permettent aux cliniciens d’évaluer la qualité osseuse chez l’adulte. Malheureusement, ces outils diagnostics ne sont pas adaptés pour l’enfant (nocivité des radiations, anesthésie ou sédation nécessaire), et le développement d’un outil clinique nécessite une bonne connaissance des propriétés du tissu osseux pédiatrique.Peu d’études ont analysé les propriétés du tissu osseux au cours de la croissance. Cette pénurie de données de référence s’explique par la faible quantité d’échantillons disponible pour les essais en laboratoire et par la qualité même de ces échantillons pour la plupart «prélevés» et associés à une pathologie de l’enfant.Les objectifs de ce travail de thèse s’inscrivent dans une logique de compréhension des mécanismes et des propriétés de l’os en croissance. L’intérêt majeur de ce travail est donc d’apporter de nouvelles connaissances sur l’os cortical pédiatrique. Les propriétés mécaniques et tissulaires ont été étudiées via l’utilisation de diverses techniques: la microtomographie, la microradiographie, la FTIRM, la biochimie, la compression, la caractérisation ultrasonore et la nanoindentation. Ce travail a permis de mettre en avant l’évolution de l’os cortical pédiatrique vers un état mature: la structure des fibres de collagène se hiérarchise, le tissu se minéralise. Ces changements dans la structure du tissu osseux lui permettent de se rigidifier. Ces travaux de thèse ont permis de mieux comprendre cette évolution, et vont permettre d’avoir une 1ère base de données sur la fibula infantile. / Bone is a material whose properties change throughout life depending on environmental constraints. Today, imaging modalities allow clinicians to assess bone quality in adults. Unfortunately, these diagnostic tools are not suitable for children (harmful radiation, anesthesia or sedation required). Development of a clinical tool requires a good knowledge of pediatric bone tissue properties.Few studies have analyzed the properties of bone tissue during growth. This lack of reference data is due to the small amount of samples available for laboratory testings and the quality of these samples for the most taken and associated with a child's illness.The aims of this thesis are to understand the growing bone. The major interest of this work is to provide new knowledge on pediatric cortical bone. Mechanical, structural and chemical properties have been studied by the use of various techniques: tomography, microradiography, FTIRM, biochemistry, compression, ultrasonic characterization and nanoindentation.This work allowed to highlight that pediatric cortical bone evolves into a mature state: maturation of collagen cross-links, mineralization of bone tissue. These changes in the structure of the bone allows it to stiffen. This work allows to understand this evolution and will enable to have a first database on child fibula.

L’os est un matériau vivant avec une structure hiérarchique complexe qui lui confère des propriétés mécaniques remarquables. L’os subit perpétuellement des contraintes mécaniques et physiologiques, ainsi sa qualité et sa résistance à la fracture évoluent constamment au cours du temps à travers le processus de remodelage osseux. La qualité osseuse est non seulement définie par la densité minérale osseuse mais également par les propriétés mécaniques ainsi que la microarchitecture. Dans le cadre de la présente thèse, on a développé une modélisation multiéchelle unifiée couplant à la fois les activités cellulaires au comportement mécanique de l'os tenant compte des différents niveaux hiérarchiques de l'os: de l’ultrastructure au remodelage osseux. Ce modèle permet d’étudier le comportement mécano-bibliologique de l’os et de prédire ses propriétés mécaniques apparentes à différentes échelles allant du nanoscopique au macroscopique en fonction des constituants élémentaires de l'os. Pour atteindre cet objectif, une démarche en quatre phases a été adoptée. La première phase consiste à décrire les constituants élémentaires de l’os. La deuxième phase avait pour objectif la modélisation multiéchelle de l'ultrastructure osseuse constituée de trois échelles nanoscopiques (microfibrille, fibrille et fibre) par la méthode des éléments finis et des réseaux de neurones. La troisième phase correspond à la modélisation des échelles micro-macroscopiques de l’os cortical (lamelle, ostéon, os cortical) en utilisant comme paramètres d’entrée les propriétés de la fibre déterminées dans la deuxième phase. Enfin, dans la dernière phase, on a développé un modèle mécano-biologique du remodelage osseux permettant de simuler le processus d'adaptation osseuse tenant compte explicitement des activités biologiques des cellules osseuses. Les propriétés mécaniques prédites par nos algorithmes multiéchelles ont servi pour alimenter le modèle de remodelage. Ce modèle a été implémenté au code de calcul d’éléments finis ABAQUS/Standard à travers sa routine utilisateur UMAT. Finalement, le modèle EF mécano-biologique multiéchelle du remodelage osseux a été appliqué pour simuler différents scénarii de remodelage sur des fémurs humains (2D et 3D). Différents facteurs ont été ainsi analysés tels que l'âge, le genre, l'amplitude des activités physiques, etc. Les résultats obtenus sont conformes (qualitativement) avec les observations cliniques et cohérents avec les différentes études expérimentales. En conclusion: (i) Les modèles unifiés ainsi développés (modèle multiéchelle, modèle mécano-biologique de remodelage osseux) contribuent à l'analyse fine du comportement de l'os humain. (ii) L'application des algorithmes a permis d'effectuer des essais virtuels pour analyser les effets combinés de nombreux facteurs caractérisant la qualité osseuse. / Bone is a living material with a complex hierarchical structure which entails exceptional mechanical properties. Bone undergoes permanent mechanical and physiological stresses, thus its quality and fracture toughness are constantly evolving over time through the process of bone remodeling. Bone quality is not only defined by bone mineral density but also by the mechanical properties and microarchitecture. The current thesis offers a multiscale modeling approach unifying the cell activity to the mechanical behavior, taking into consideration the hierarchical levels of bone, from the ultrastructure to bone remodeling. This model permits to study the mechanobiological behavior and to predict the mechanical properties of the bone at different scales from nano to macro depending on the elementary constituents of bone. To achieve the objective of the current work, an approach of four phases was adopted. The first phase is to describe the basic components of the bone. The second phase concerns the multiscale modeling of the three nanoscopic levels of bone ultrastructure (microfibril, fibril and fiber) by the finite element method and neural networks. The third phase aims to model the micro-macroscopic structures of cortical bone (lamella, osteon, cortical bone) using the fiber properties predicted from the second phase as input parameters. In the last phase, a mechano-biological model of bone remodeling was achieved to simulate the process of bone adaptation explicitly considering the biological activities of bone cells. Mechanical properties predicted by our multiscale algorithms were used to feed the remodeling model. This model has been implemented into the ABAQUS/Standard finite elements code as a user subroutine. Finally, the finite element mechano-biological multiscale model of bone remodeling was applied to simulate different scenarios on human femurs (2D and 3D). Hence, different factors such as: age, gender, physical activities, etc were analyzed. The obtained results are conformed (qualitatively) to clinical observations and consistent with the various experimental studies. In summary, (i) the models portrayed here (multiscale model, mechanical-biological model of bone remodeling) contribute by their unified approach to the realistic modeling of the response of human bone. (ii) The application of the algorithms permits to perform virtual experiments to scrutinize the combined effects of numerous factors dictating the bone quality.

L'hypoxie périnatale entraîne une dégénérescence et un délai de maturation des oligodendrocytes et des neurones corticaux du cortex cerebral. Mon projet de thèse a d'abord consisté à étudier la contribution des cellules souche neurales de la zone sous-ventriculaire dorsale (dSVZ) à la tentative de régénération spontanée observée après la lésion. Dans un second temps, j'ai étudié la capacité de ces cellules souches à être manipulée en utilisant une approche pharmacologique.Mes résultats mettent en évidence une réponse spontanée et dynamique de la dSVZ qui produit des neurones et des oligodendrocytes corticaux en réponse à l'hypoxie. L'administration par voie intranasale d'un inhibiteur de Gsk3b, qui active la voie Wnt/b-caténine, petite molécule identifiée à l'aide d'une étude bio-informatique comme « dorsalisante », juste après la période d'hypoxie, potentialise cette réponse spontanée. En effet, mes résultats montrent que certains neurones corticaux issus de la dSVZ survivent avec le traitement alors qu'aucun ne semblent persister après 1 mois suivant l'hypoxie. De plus, le traitement accélère la maturation des oligodendrocytes corticaux et augmentent leur production et intégration à long terme. Enfin, le traitement a un effet à long terme sur les cellules souches de la dSVZ en augmentant la proportion de ces cellules qui sont actives. Pour conclure, la dSVZ participe à la récupération corticale spontanée qui suit l'hypoxie périnatale et cette réponse peut être potentialisée par l'administration d'une petite molécule identifiée par notre analyse bio-informatique, un inhibiteur de GSK3b / Perinatal hypoxia leads to degeneration and delayed maturation of oligodendrocytes and cortical glutamatergic neurons. My PhD project consists in assessing the contribution of neural stem cells (NSCs) of the dorsal subventricular zone (dSVZ, i.e. the largest germinal zone of the postnatal brain) to the spontaneous regenerative attempt observed following such injury as well as its amenability to pharmacological manipulation.The results I have obtained highlight a dynamic and lineage-specific response of NSCs of the dSVZ to hypoxia that results in de novo oligodendrogenesis and cortical neurogenesis. Newborn cortical neurons express appropriate cortical layer markers, supporting their appropriate specification. A pharmacogenomics analysis allowed us to identify small molecules boosting specificly dSVZ NSCs. Pharmacological activation of Wnt/ß-catenin signalling by intranasal GSK3ß inhibitor administration during the recovery period following hypoxia indeed potentiates dorsal SVZ participation to post-hypoxia repair. Gsk3b inhibitor CHIR99021 seems to promote survival of cortical neurons from the dSVZ produced in response to hypoxia. More interestingly, CHIR99021 promotes oligodendrocyte maturation and long term integration in the cortex as well as a long term increased activity of dSVZ NSCs.Altogether, my results highlighted a dynamic and lineage-specific response of dorsal NSCs cells to hypoxia and identify the early postnatal dorsal SVZ as a malleable source of stem cells for cortical repair following trauma that occur early in life. CHIR99021 (a Gsk3b inhibitor) intranasal administration promotes this cortical cellular repair with a long term activation of dSVZ NSCs which increased their production of oligodendrocytes migrating to the cortex and a short term improvement of their maturation, and might allow the integration of cortical neurons they produce

A displasia cortical focal (DCF) é uma das causas mais frequentes de epilepsia refratária. Na clínica, diferentes informações são usadas para localizar o foco epileptogênico, mas nenhum método é autossuficiente para evidenciar o local original das crises, associado com a presença da DCF. Embora haja relatos na literatura indicando alterações no padrão de distribuição de tons de cinza e morfologia dos voxels decorrentes da DCF, algumas limitações dos métodos desenvolvidos ainda impedem a utilização clínica. Nossa proposta foi investigar a capacidade de identificar DCF através de análises de espessura cortical e padrões de textura em imagens estruturais de Ressonância Magnética (RM), validando os métodos desenvolvidos a partir uma base de imagens retrospectiva, cujo tecido epileptogênico já havia sido ressecado e a DCF confirmada em análise histológica. A caracterização das DCF foi feita a partir da segmentação automática de tecido cortical saudável em conjunto com a segmentação manual da DCF feita por um especialista, e consiste na geração de mapas de característica e extração de valores de distribuições para comparação em análise estatística. Investigamos também a eficácia da detecção de DCF através do uso de algoritmos de aprendizado de máquina para classificação automática. Obtivemos precisão 0,81 e sensitividade 0,87, colocando o método desenvolvido em par com outros métodos presentes na literatura. Entretanto, foi identificada uma grande dependência do desempenho de métodos de pré-processamento, como corregistro e segmentação automática. / Focal Cortical Dysplasia (FCD) is one of the most frequent causes of refractory epilepsy. In clinical procedures, the information gathered from different techniques is used in order to locate the epileptogenic focus, associated with the presence of FCD. However, there is no self sufficient method to evidence the presence and location of such lesions and especially its extension. Although there are reports indicating change in gray scale intensity patterns and voxel morphology in the presence of DCF, limitations in developed methods still prevent their clinical use. Our proposal was to investigate the capability of identifying FCD through cortical thickness and texture patter analysis in structural MRI images, validating developed methods by utilizing a retrospective base of images from patients that were subjected to surgery, with the FCD being confirmed in histological analysis. Characterization of FCD was achieved from automatic segmentation of healthy cortex and manual segmentation of FCD tissue made by an specialist, and consists in the generation of texture or structural feature maps and comparison of distribution values in healthy or FCD tissue with statistical analysis. We also investigate the efficiency of FCD detection with Machine Learning automatic classification, obtaining precision of 0,81 and sensitivity of 0,87, placing our method on par with other methods in the literature. However, there is a major performance dependency of proposed method with pre-processing steps, like registration and automatic segmentation.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-12-01T12:26:58Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Mariana Barros.pdf: 1911747 bytes, checksum: f5c0832d347da9436db27522938984b9 (MD5) / Made available in DSpace on 2016-12-01T12:26:59Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Mariana Barros.pdf: 1911747 bytes, checksum: f5c0832d347da9436db27522938984b9 (MD5) Previous issue date: 2016-02-26 / CAPES / A nutrição no início da vida e o exercício físico podem alterar a excitabilidade cerebral, interferindo em processos de desenvolvimento e em parâmetros eletrofisiológicos. A depressão alastrante cortical (DAC) é um fenômeno relacionado com a excitabilidade cerebral. Em estudos anteriores, demonstramos potenciação da atividade elétrica cortical espontânea (ECoG) após a DAC. Nesta tese investigou-se a influência das condições de lactação e do exercício de natação, no início da vida e na idade adulta, sobre essa potenciação. Ratos Wistar machos foram amamentados em ninhadas com 6 ou 12 filhotes (grupos L6 e L12). A natação, precoce e tardia, foi realizada entre 8-23 e 60-75 dias de vida, respectivamente. O ECoG foi registrado aos 90-120 dias. Com um algoritmo específico (software Matlab™), determinou-se a amplitude do ECoG. Diferenças intergrupos de peso corporal e encefálico (L12<L6) confirmaram a deficiência nutricional do grupo L12. Diferenças, no mesmo animal, entre as amplitudes do ECoG antes e depois da DAC confirmaram a potenciação pós-DAC. Um grupo que não sofreu DAC não apresentou potenciação do ECoG. A natação precoce reduziu, e a tardia aumentou, essa potenciação do ECoG. A deficiência nutricional (condição L12) atenuou esse efeito. Estes dados sugerem que “condição de lactação”, “exercício de natação” e “idade ao exercício” modulam a potenciação do ECoG. A relevância desses resultados na fisiopatologia de doenças neurológicas dependentes da excitabilidade cerebral, como enxaqueca com aura e epilepsia, merecem futura investigação. / Nutrition in early life and physical exercise can alter brain excitability, interfering with development processes and electrophysiological parameters. Cortical spreading depression (CSD) is a phenomenon related to brain excitability. In previous studies, we demonstrated spontaneous brain electrical activity (ECoG) potentiation after CSD. In this thesis investigated the influence of the lactation conditions and swimming exercise in early life and adulthood, on this potentiation. Male Wistar rats were suckled in litters with 6 or 12 pups (L6 and L12 groups). The swimming, early and late, was carried out between 8-23 and 60-75 days of age, respectively. The ECoG was recorded at 90-120 days. With a specific algorithm (software Matlab ™), we determined the amplitude of the ECoG. Intergroup differences in body- and brain- weight (L12 <L6) confirmed the nutritional deficiency of the L12 group. Differences, in the same animal, between ECoG amplitudes before and after the CSD confirmed the post-CSD potentiation. A group that did not suffer CSD displayed no ECoG potentiation. Early swimming reduced, and later increased, this ECoG potentiation. The nutritional deficiency (L12 condition) attenuated this effect. These data suggest that "lactation condition", "swimming exercise" and "age to exercise" modulate ECoG potentiation. The relevance of these findings in the pathophysiology of brain excitability-dependent neurological diseases, such as migraine with aura and epilepsy, deserve further investigation.

O conhecimento adquirido sobre a síndrome de Eagle demonstra que sua sintomatologia pode ser confundida muito facilmente com outros tipos de desordens craniomandibulares, principalmente a disfunção temporomandibular (DTMs). A falta de conhecimento sobre a síndrome de Eagle e as alterações morfológicas na cadeia estilo-hióidea podem vir a determinar a execução de tratamentos errôneos em pacientes com a síndrome. O objetivo do estudo foi encontrar uma possível correlação entre a presença de DTMs e o alongamento do processo estilóide e também analisar a existência de associação entre a qualidade óssea mandibular e a presença de calcificação da cadeia estilo-hióidea. Para tanto foram analisados 50 pacientes com DTM, confirmada a partir do RDC/TMD. Foi feito o exame clínico e realizado um questionário com questões direcionadas à síndrome de Eagle. Também foi realizada a documentação radiográfica de cada paciente, composta por: radiografia panorâmica digital, cefalométrica lateral digital, radiografia ântero-posterior digital e radiografias transfaciais digitais para analise da cadeia estilo-hióidea. Para a análise das radiografias foi utilizado o programa computacional Radiocef (Radiomemory, Belo Horizonte, Brasil), onde foram realizados traçados cefalométricos por análise específica, e medidas lineares e ângulares do processo estilóide. Nas radiografias panorâmicas foram realizadas medições bilaterais do comprimento do processo estilóide e realizada a classificação morfológica da cadeia estilo-hióidea (LANGLAIS, 1986). Nas radiografias cefalométricas foram realizadas medições do comprimento e angulação anterior do processo estilóide. Nas radiografias ãntero-posterior foram realizadas as medições bilaterais do ângulo medial do processo estilóide. E nas radiografias transfaciais foram feitas as avaliações nas ATMs. Foi feita também medições do Indice Cortical (IC) bilateralmente nas radiografias panorâmicas. Cada radiografia foi traçada e medida por três vezes, com intervalos de tempo de 1 mês entre as medições, sendo as médias posteriormente analisadas a fim de diluir o erro entre as medidas. Foi realizado a estatística através do Programa Biostat 4.0 e o teste de Pearson (p=0,001). Como resultados, foi encontrada uma incidência de 76% de alongamento do processo estilóide na amostra. Houve correlação positiva para as medidas bilaterais realizadas na radiografias panorâmicas (p<0,001) e também para as medidas de comprimento do processo estilóide realizados nas diferentes tomadas radiográficas panorâmicas e cefalométricas laterais (p<0,001). Não houve correlação significativa entre as medidas de angulação medial realizadas bilateralmente (p=0,0011). Foi encontrado 2 pacientes (4%) com síndrome de Eagle clássica. Não foi encontrada associação positiva entre as medidas de comprimento, angulação do processo estilóide e os sintomas. Foi encontrada diferença estatística entre o IC. Concluiu-se que, há prevalencia de alongamento do processo estilóide em pacientes com DTM. Embora não foi encontrada relação entre as medidas realizadas na cadeia estilo-hióidea com os sintomas de cefaléia, dor orofacial, zumbido e vertigem. / The relationship between temporomandibular disorders and Eagle\'s syndrome occurs due to the similarity of symptoms. The knowledge gained about the Eagle\'s syndrome shows that its symptoms can be very easily confused with other types of craniomandibular disorders and numerous other diseases found in regions of the skull, face and neck. The lack of informations about the Eagle\'s syndrome and the morphological alterations in the stylohyoid complex may come to determine erroneous treatments in patients with the syndrome. The aim of this study was to find a possible correlation between the presence of TMD and elongation of the styloid process and to examine the possible association between mandibular bone quality and calcification of the stylohyoid complex. Therefore, it analyzed 50 patients with TMD, confirmed from the RDC / TMD. Clinical examination was made and carried out a questionnaire aimed at the Eagle syndrome. Was also performed radiographic documentation of each patient, consisting of: digital panoramic radiograph, lateral cephalometric digital radiography, anteroposterior digital radiographs and digital transfacial radiographs. For the analysis of radiographs were used computational Radiocef software (Radiomemory, Belo Horizonte, Brazil), being performed by specific analysis cephalometric tracing, and linear and angular measurements of the styloid process. Panoramic radiographs were made in bilateral measurements of the length of the styloid process and performed the morphological classification of the stylohyoid chain (Langlais, 1986). In cephalometric radiographs were performed measurements of length and angulation of the styloid process earlier. Radiographs anteroposterior measurements were taken of the bilateral medial angle of the styloid process. And radiographs transfacials the assessments were made in ATMs. Each radiograph was traced and measured three times with intervals of one month between the measurements and the averages were then analyzed in order to spread the error between the measurements. Was accomplished through the statistical program Biostat 4.0 and Pearson test (p=0.001). As a result, we found an incidence of 76% elongation / mineralization of the styloid process in the sample. There was a correlation between the bilateral measures taken in panoramic radiographs (p<0.001) and also for measures of length of the styloid process carried out in different panoramic radiographs and lateral cephalometric (p<0.001). There was no significant correlation between measures of medial angulation performed bilaterally (p=0.0011). No positive association was found between the measures of length, angulation of the styloid process and symptoms. It was concluded that there is prevalence of elongated styloid process in patients with TMD. Although no relationship was found between measurements at stylohyoid chain with symptoms of headache, orofacial pain, tinnitus and vertigo.

INTRODUÇÃO: A obtenção de medidas de excitabilidade cortical mediante a estimulação magnética transcraniana tem surgido nos últimos anos como método de avaliação da integridade funcional do trato cortico-spinal e rede interneuronal no córtex primário motor, abrindo perspectiva de utilizá-la na prática clínica. Alterações nos parâmetros de excitabilidade cortical tem sido relatados na síndrome fibromiálgica e outras síndromes dolorosas, se correlacionando com a gravidade de diferentes componentes dessas síndromes e mudando conforme o tratamento. Entretanto, apesar do seu potencial benefício, existe uma pequena quantidade de estudos disponíveis na literatura que tenham proposto a obtenção de dados de normalidade para esses parâmetros, com casuísticas pequenas, não pareadas por fatores que potencialmente alteraram seus valores. O presente estudo procurou montar uma curva de normalidade de parâmetros de excitabilidade cortical com cálculo de amostra, pareamento por idade e sexo, com estudo dos efeitos da lateralidade hemisférica e dominância, fase do ciclo menstrual e variabilidade inter e intraexaminador. MÉTODOS: Após cálculo amostral, foram convocados voluntários saudáveis do sexo masculino e feminino, pareados por idade. No total, 216 voluntários completaram o estudo. O potencial evocado motor, inibição intracortical e facilitação intracortical foram medidas no músculo primeiro interósseo dorsal após estímulo dos córtices motor primário bilateral. O grupo de 15 mulheres fez a primeira medição do uso de anticoncepcional oral e a segunda medição na fase de descanso do mesmo. A variabilidade interexaminador e intraexaminador foi aferida em 20 voluntários para cada uma das situações. RESULTADOS: A comparação entre os parâmetros de voluntários menores que 50 anos e maiores que 50 anos mostrou diferenças significativas. Foram obtidos os valores de normalidade para menores de 50 anos e maiores de 50 anos (média e desvio padrão): 1.Menores ou igual que 50 anos: LMR: 49 ± 9,39%; PEM 120%: 587,63±779,52 V; MEP 140%: 1413,08±1343,18 V; MEP 120/140%: 3,83±5,39 V; IIC 2ms: 0,40 ±0,44 V; IIC 4ms: 0,61± 0,84 V; IIC: 0,56± 0,63 V; FIC 10ms: 1,95 ±1,82 V; FIC 15ms: 1,80±1,73 V; FIC: 1,87±1,64 V. 2. Maiores de 50 anos: LMR: 49,1 ± 9.58%; PEM 120%:467,71±650,61 V; PEM 140%:1172,43±1158,47 V; PEM 120/140%: 4,04±4,27 V; IIC2ms: 0,73± 1,26 V; IIC 4ms: 1,04±1,67 V; IIC:0,81±1,03 V; FIC 10ms:2,46±3,85 V; FIC 15ms: 2,12±3,05 V; FIC: 2,28±3,32 V. Houve semelhança entre homens e mulheres( p>0,3). Os córtices motores direito e esquerdo apresentaram parâmetros semelhantes de excitabilidade cortical (p>0,25) para todas as análises. Assim, os valores para o hemisfério direito e esquerdo e os dados de homens e mulheres foram agrupados. Não houve diferença estatística significativa entre destros e sinistros (p>0,20). A variabilidade inter e intraexaminador é alta para a maior parte dos parâmetros, porém, com alta correlação para o limiar motor em repouso e potenciais evocados motores. A inibição e facilitação cortical tiveram baixa correlação, mas confiabilidade aceitável. Não houve diferença importante entre a quantidade de medidas anormais obtidas entre as fases do ciclo menstrual com ou sem o uso do anticoncepcional oral. CONCLUSÕES: Foram levantados os parâmetros de normalidade para adultos saudáveis acima e abaixo de 50 anos. A idade não tem um efeito linear sobre a excitabilidade cortical. Não há diferenças significativas entre sexo, lateralidade de hemisfério ou dominância sobre parâmetros de excitabilidade cortical. Não há correlação significativa entre as fases de uso de anticoncepcional oral e do seu descanso (período menstrual) com as medidas de excitabilidade cortical / BACKGROUND AND AIMS: Measures of cortical excitability parameters by transcranial magnetic stimulation have gained increasing interest as a way to obtain information on the functional integrity of the cortico-spinal tract and interneuronal networks within the primary motor cortex. Changes in cortical excitability parameters have been reported in fibromyalgia and neuropathic pain syndromes showing correlation with the severity of different symptoms of these pain syndromes, and seeming to change during treatment. Despite its potential use, there is a paucity of normative data for cortical excitability parameters. We aimed to obtain normative data for cortical excitability in healthy volunteers. METHODS: A sample size of men and women were matched according to age. In total 216 healthy volunteers completed the study. Rest motor threshold (RMT), motor evoked potentials (MEP), intracortical inhibition (ICI) and facilitation (ICF) were measured in the first dorsal interosseous muscle for both primary motor cortex A group of 15 women were measured twice, first during use of oral contraceptive and a second measure was obtained when not in use of it (menstruations phase). The inter and intrainvestigator variability was assessed in a sample of 20 healthy volunteers. RESULTS: The comparison between the cortical excitability parameters from volunteers younger than 50 years old and volunteers older than 50 years showed significant differences. Normative data for younger than 50 years and older than 50 years were obtained (mean and standard deviation): 1. Age of 50 years or younger: RMT: 49 ±9.39%; MEP120%: 587.63±779.52 V; MEP140%: 1413.08±1343.18 V; MEP120/140%: 3.83±5.39 V; ICI2ms: 0.40 ±0.44; ICI4ms: 0.61 ±0.84 V; ICI: 0.56±0.63 V; ICF10ms: 1.95 ±1.82 V; ICF15ms: 1.80±1.73 V; ICF: 1.87±1.64 V. 2. Older than 50 years: RMT: 49.1±9.58%; MEP120%: 467.71±650.61 V; MEP140%: 1172.43±1158.47 V; MEP120/140%: 4.04±4.27V; ICI2ms: 0.73± 1.26 V; ICI4ms: 1.04±1.67 V; ICI: 0.81±1.03 V; ICF10ms:2.46±3.85 V; ICF15ms: 2.12±3.05 V; ICF: 2.28±3.32 V. There was similarity between genders (p>0,3.) There was no difference between left and right hemispheres (p>0,25). Consequently data from both hemispheres and genders were grouped. There was no significant statistical difference between handedness. We found a good inter/intrainvestigator correlation for RMT and MEP. ICI and ICF had low correlations but an acceptable reliability. CONCLUSIONS: We reported normative data for cortical excitability in adult individuals younger and older than 50 years old. Age has a non-linear effect on cortical excitability. We found no left-right cortex asymmetries or differences related to gender or handedness. We found no correlation between the phases of contraceptive use and the menstruation phase and the cortical excitability parameters