El Balonmano es uno de los deportes de equipo más practicados en Europa, España y Cataluña. Este deporte, presenta valores altos en cuanto a incidencia y riesgo de lesiones. El análisis respecto al patrón de lesiones, incidencia y algunos factores de riesgo, en ocasiones hallan conclusiones controvertidas, y son muy escasos los estudios que analizan ésta problemática en las etapas formativas tomando en consideración el proceso madurativo como un condicionante. Por ello se plantea la presente investigación con un trabajo inicial retrospectivo (primer artículo) durante cinco temporadas sobre el estudio de la epidemiologia de las lesiones del balonmano de elite en las diferentes categorías de edad, comparando los jugadores profesionales con aquellos en etapas formativas. Si bien no se encuentran diferencias significativas en la incidencia lesional por edades ni categorías, si se encuentran diferencias en el patrón lesional: las estructuras más afectadas son tobillo y rodilla y las lesiones musculares son más prevalentes en adultos profesionales y las ligamentarias en jóvenes en formación. Continúa el proyecto con un estudio prospectivo durante dos temporadas consecutivas que generan dos artículos originales: un segundo artículo que forma parte del trabajo principal de ésta tesis y un tercer artículo, complementario, que se incorpora en el anexo. El segundo artículo, analiza las variables de maduración en todas sus variantes respecto a incidencia de lesiones por mil horas de exposición total, y durante entrenamientos o competiciones. Si bien no se detectaron diferencias significativas en la incidencia lesional por categoría de edad o estado madurativo, sí se constatan diferencias significativas durante la competición según la categoría de edad, y durante los entrenamientos según el estado madurativo del jugador. En el tercer artículo, se analiza el rol de la posición de juego en la incidencia de lesiones según sucedan en adultos o jóvenes, y en éstos últimos según sean maduros o inmaduros. No se encontraron diferencias significativas. Sin embargo si se encontró que los jugadores de segunda línea presentaban más problemas de rodilla y en concreto lesiones de cartílago y que los jóvenes inmaduros presentaban un mayor riesgo de sufrir apofisitis. En conclusión parece que el riesgo lesional por horas de exposición no parece ser determinante en el Balonmano, sin embargo el patrón lesional si es diferente por categorías de edades y estados madurativos. Ello debe ser considerado por entrenadores y resto de profesionales implicados, para poder desarrollar programas de entrenamiento y protocolos lesionales preventivos más específicos durante cada etapa de formación hasta la elite del balonmano profesional. / Handball is one of the most popular team sports in Europe, Spain and Catalonia. This sport shows high values for incidence and risk of injuries. The analysis regarding pattern of injuries, incidence, and risk factors, results in controversial findings, and very few studies analyze this problem in the academy period, considering the maturity process as a variable. We proposed this line of research with a first study (retrospective study design). We analyzed the epidemiology of injuries in elite handball in different age categories, comparing the professional and academy players, over five seasons. There was no difference in total injury incidence nor by age nor by category, but we found differences in injury pattern; the most affected parts being ankle and knee, and muscle injuries were more frequent in professional adults, and ligament injuries in youth. This was followed by a prospective study, over two consecutive seasons, which generated two original manuscripts (second and third). The second manuscript being a main part of this thesis, and a third manuscript being incorporated in the annex. The second manuscript analyzes the relationship between maturity stage and injury incidence (per 1000 hours of total exposure, training and match). There is no difference by age category or biological maturity compared to the total injury incidence, but there is a significant difference in competition between injury incidence and age category or during training between injury incidence and biological maturity. The third manuscript, studies the role of playing position and injury incidence in adults versus young people, and in this last group with respect to biological maturity. There is no difference in total injury incidence. However, we found that second line players had more knee problems and specifically cartilage injuries and the immature youth players a higher injury risk of suffering apophyisitis. In conclusion, it seems that the injury risk per exposure hours is not determinant in handball, however the injury pattern is different by age and maturity stage. This should be taken into account by coaches and technical staff when developing training programs and preventive protocols for each formative stage up to professional elite handball

PSYCHOLOGICAL SYMPTOMS IN ANKYLOSING SPONDYLITIS. STUDY OF THEIR PREVALENCE AND DETERMINANTS INTRODUCTION: In recent years the importance of psychological factors in inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus has been recognized. However, in Ankylosing Spondylitis (AS) little attention has been paid to these factors; few studies have evaluated the presence of psychological disorders in this disease. OBJECTIVE: To establish the prevalence of symptoms of anxiety and depression in patients with AS and to identify demographic, clinical, analytical, metrological and radiological data that may predict their presence.PATIENTS AND METHODS: Cross-sectional study performed in 160 AS patients attended in accordance with a standard protocol. The following variables were evaluated: age, sex, marital status, educational level, employment status, time of evolution, age of onset, presence of peripheral arthritis, visual analogue scale (VAS) of pain, night pain, disease activity evaluated by patient (VAS), presence of uveitis, previous surgery, comorbidity, smoking habit, BASFI, HAQEA, BASDAI, HLA B27, ESR, RCP, modified Schober test, thoracic expansion, occiput-wall distance, radiological sacroileitis and BASRI of cervical and lumbar spine and hips. Depression was assessed with the adapted Spanish language version of Beck's Depression Inventory (BDI). Scores of 18 or above were taken as representative of depression. Anxiety was assessed by the State Trait Anxiety Inventory (STAI) including the subscales of Trait (T) and State (S). Scores of 8 or above on either subscale were considered to reflect presence of Anxiety symptoms. In the statistical study, we performed a descriptive study and an analytical study including bivariate and multivariate analyses with logistic regression models for qualitative variables and linear regression models for quantitative variables.RESULTS: Symptoms of Depression were found in 23.1% of patients, State Anxiety in 23.1% and Trait Anxiety in 24.4%. BDI and STAI S and T scores were associated with pain, night pain, disease activity evaluated by the patient, BASFI, HAQEA, BASDAI and BASRI in lumbar spine. BDI scores were associated with Anxiety. STAI S scores were also associated with BDI and STAI T and STAI T scores with comorbidity, ERS, Modified Schober's test, BDI and STAI S. In Hierarchical Regression Analysis, BASFI was the only independent variable associated with Depression and Anxiety. Variables included in this analysis explained 26.4% of values for Depression, 24.4% for STAI S and 23.7% for SRAI T.CONCLUSIONS: Psychological symptoms of Depression and Anxiety are frequent in patients with AS and are related fundamentally to activity and functional capacity. The functional capacity observed by BASFI is the only independent determinant of the presence of psychological symptoms. An association was found between symptoms of Depression and symptoms of Anxiety.

INTRODUCCIÓN La mucositis es uno de los efectos secundarios más frecuentes cuando un paciente es sometido a terapias contra el cáncer. Su incidencia está entre un 20-40% de los pacientes que reciben quimioterapia convencional, y un 80% de los pacientes con trasplantes de médula ósea y que han recibido radioterapia de cabeza y cuello. La complejidad del proceso de reparación de los tejidos, está influenciada por diferentes factores. La apigenina es un flavonoide natural con propiedades antiinflamatorias e antioxidantes, y posee la capacidad de neutralizar radicales libres. OBJETIVOS Objetivo general: El objetivo de este estudio fue evaluar el efecto de la administración de apigenina potásica o dexametasona sobre un modelo animal de mucositis oral inducida por el quimioterapéutico 5- Fluorouracilo. Objetivos específicos Reproducir el modelo experimental de mucositis oral en hámsters mediante la aplicación sistémica del quimioterapéutico 5- Fluorouracilo. Evaluación clínica de las lesiones orales desarrolladas y su evolución con la administración tópica de apigenina potásica o dexametasona, y estudiar los cambios producidos en los distintos tiempos de sacrificio (5, 7,10 y 14 días). Analizar mediante el estudio anatomopatológico el área de mucositis oral, y valorar los cambios orales a los 5, 7,10 y 14 días de la aplicación apigenina potásica o dexametasona. MATERIALES Y MÉTODOS Para la realización de este estudio, se utilizaron 36 hamsters Sirios que fueron divididos en 3 grupos, de los cuales se obtuvo 72 muestras: Control (50% ácido acético + 5-FU); grupo II (50% ácido acético + 5-FU + Dexametasona); grupo III (50% ácido acético + 5-FU + Apigenina Potásica). Seis animales de cada grupo fueron sacrificados en los días 5,7, 10 y 14, una vez inducida la mucositis. Las úlceras fueran clasificadas mediante un sistema de puntuaciones clínicas. El estudio histomorfométrico se realizó para cuantificar el número de células inflamatorias en las lesiones. RESULTADOS El proceso de curación en el grupo control fue más lento en comparación con los grupos tratados con Dexametasona y Apigenina. Se observan diferencia estadísticamente significativas entre el grupo tratado con Apigenina potásica con respecto a los otros dos grupos en el día 10 del experimento. El infiltrado inflamatorio era menor en el grupo de la Apigenina potásica en los días 7 y 10 del estudio, en comparación con el resto (p<0,05). No se observan diferencias estadísticamente significativas en los tres grupos durante el día 5 y 14 del experimento. CONCLUSIONES Una vez establecidos los objetivos y habiendo analizado los resultados, las conclusiones derivadas de este estudio son las siguientes: 1. La aplicación de 5-fluoruracilo y ácido acético originó, en todos los animales del estudio, la aparición de mucositis oral en el área tratada, confirmando la idoneidad del modelo animal empleado. 2. El tratamiento con apigenina potásica provocó la mejora de las lesiones ulcerosas respecto al control, tanto en la valoración clínica como en la histomorfométrica, donde existían diferencias estadísticamente significativas en el décimo día. 3. El efecto de la apigenina potásica en el modelo empleado fue similar e incluso superior en algunos aspectos y tiempos, al del corticoide dexametasona, lo que sugiere que podría tratarse de un agente de origen natural útil para el tratamiento de la mucositis oral. / INTRODUCTION Mucositis is an important side affect of cancer therapy, occurring in nearly 20% to 40% of patients receiving conventional chemotherapy, 80% of those under high-dose chemotherapy as conditioning for hematopoietic stem cell transplantation and nearly all patients receiving head and neck radiation therapy. Tissue repair complexity may be influenced by different factors. Naturally occurring flavonoids, like apigenin, have been shown to possess anti-inflammatory properties related to their antioxidant and free radical scavenging ability. PURPOSE General objective: - The aim of this study was to evaluate the effect of administration of apigenin potassium or dexamethasone on an animal model of oral mucositis induced by 5-fluorouracil chemotherapy. Specific objectives: - Replicate the experimental model of oral mucositis in hamsters by the systemic application of 5-fluorouracil chemotherapy. - Evaluate clinically the developed oral lesions and its evolution with topical administration of potassium apigenin or dexamethasone, and study the changes at different times of sacrifice (5, 7, 10 and 14 days). - Analyse by anatomopathological study the area of oral mucositis, and evaluate oral changes at 5, 7,10 and 14 days of application potassium apigenin or dexamethasone. MATERIALS AND METHODS Seventy-two male Syrian hamster were divided into three groups, and 72 samples were obtained: control (50% acetic acid + 5-FU); 50% acetic acid + 5-FU + Potassium Apigenin (KA) and 50% acetic acid + 5-FU + Dexametasone. Six animals from each group were sacrificed 5, 7, 10 and 14 days after inducing the mucositis; ulcers were assessed by imaging analysis using a scoring system (Cho, 2006). The number of inflammatory cells in the ulcerated region was quantified in all periods through histomorphometric analysis (H&E). RESULTS The healing process of the control group was slower than that of KA and Dexametasone-treated groups. There was significant difference between KA and control group in the 10-day period. Lower quantity of inflammatory cells in the KA treated group in comparison to control group in the 7- and 10-day periods was observed (p<0.05). No statistically significant difference was verified among the groups in 5- and 14-day periods. CONCLUSIONS After having established the objectives and the results analised, the conclusions of this study are: 1. Application of 5-fluorouracil and acetic acid resulted, in all animals of the study, in the occurrence of oral mucositis in the treated area, confirming the suitability of the used animal model. 2. Treatment with potassium apigenin caused the improvement of ulcerative lesions compared to the control group,in both the clinical assessment and the histomorphometry, where there were statistically significant differences on tenth day. 3. The effect of apigenin potassium in the model used was similar and even superior in some ways and times, to the steroid dexamethasone, suggesting that it could be a useful natural origin agent for the treatment of oral mucositis.

The dorsal dentate gyrus (DDG) of the hippocampus plays a role in the expression of different forms of flexible behaviour mainly due to its ability to sustain neurogenesis throughout life. In the present thesis, we examined the role that the DDG and its adjacent areas, both collectively referred to as dorsal medial hippocampus (DMH), play in flexible, adaptive behaviour and cognitive processing. We used the neurotoxin, colchicine, to induce lesions of the DDG, which were found to affect neighbouring areas. Thus these lesions will be referred to as lesions of the DMH. In the first experiment, rats were tested for (1) perseverative behaviour before and after receiving chronic methamphetamine (METH) treatment, (2) METH-induced locomotor activity and stereotypy in an open field, and (3) working memory in a T-maze. The results showed that rats with lesions of the DMH exhibited perseveration and supersensitivity to the locomotor- and stereotypy-inducing effects of METH (0, 0.1, 0.3, 1 mg/kg i.p.) as well as increased long-term METH sensitization. Rats with DMH lesions also showed significant working memory deficits. Taken together, these results reveal specific forms of behavioural inflexibility in rats with lesions of the DMH that are mainly associated with perseveration, drug-related behaviours, including stimulant motor supersensitivity and drug sensitization, and impaired working memory functions.

The human body is an over-actuated multibody system, as each joint degree of freedom can be controlled by more than one muscle. Usually, optimization techniques are used to solve the muscle force sharing problem, that is, finding out how the resultant joint torque is shared among the muscles spanning that joint. The reduction of muscle force redundancy can be achieved in several ways. Although the strategy followed by the central nervous system (CNS) to activate the muscles is not completely clear, one of the most used hypotheses to overcome this redundancy is to consider that the CNS minimizes a physiological variable. In the first study presented in this thesis, the solution to the muscle force sharing problem was approached by minimizing the sum of squared normalized muscle forces. For this purpose, a weighted cost function was designed to evaluate which muscles were more penalized in a subject with anterior cruciate ligament (ACL) deficiency during walking. The results showed that the cost function that best fitted normalized electromyography signals with muscle activations did not treat all muscles equally. Another way to reduce muscle redundancy is using the idea that muscles are activated synergistically when performing a task. In the second study, a muscle synergy analysis was carried out to compare the muscle activation information at two levels: onset-offset activation patterns and muscle synergy components of a sample of 18 ACL-deficient subjects and a sample of 10 healthy subjects. Some differences were found at both levels, what suggests that ACL-deficient subjects alter the muscle activations of their injured leg to stabilize the joint. Finally, in the third study, muscle synergies were used in a two-step optimization method to predict physiologically consistent muscle and knee contact forces, while calibrating muscle parameters. In the outer level, muscle parameters were calibrated; while, in the inner level, muscle activations were calculated using the current muscle parameters. The results showed that a set of muscle parameters were able to reproduce knee contact forces with high accuracy when knee contact forces were used during the calibration process. This study shows the main differences when these forces are available for calibrating muscle parameters and when they are not. The most important differences in the muscle parameter calibration affected lateral muscles. Therefore, this fact suggests that trials where lateral muscles play a more important role should be used to obtain a better calibration when no contact forces are available. / El cos humà és un sistema multisòlid sobreactuat, ja que cada grau de llibertat pot estar controlat per més d’un múscul. Per resoldre el problema d’indeterminació en el càlcul de les forces musculars, es sol utilitzar un mètode d’optimització. Consisteix en distribuir els moments articulars resultants entre els diferents músculs que actuen a l’articulació, i per tant, estimar la força que aquests realitzen. La reducció de la indeterminació en el càlcul de les forces musculars es pot aconseguir de diferents maneres. Malgrat que l’estratègia que fa servir el sistema nerviós central (SNC) per activar els músculs no es coneix amb exactitud, una de les hipòtesis més utilitzades per solucionar la indeterminació és el fet de considerar que el SNC minimitza una variable fisiològica. El primer estudi presentat en aquesta tesi tractava de resoldre el problema del repartiment muscular minimitzant la suma de les forces musculars normalitzades al quadrat. Per a tal fi, es va utilitzar una funció de cost ponderada per avaluar quins músculs es penalitzen més en la marxa d’un subjecte amb el lligament creuat anterior trencat. Els resultats mostren que la funció de cost que millor aproximava les activacions musculars amb el senyal d’EMG mesurat no tractava tots els músculs per igual. Una altra manera de reduir la indeterminació en el càlcul de les forces muscular és utilitzar la idea que els músculs s’activen sinèrgicament quan l’ésser humà realitza un moviment. En el segon estudi, es presenta una anàlisi de les sinergies musculars que compara la informació de les activacions a dos nivells: en els patrons d’activació-desactivació i en els components de les sinergies musculars d’una mostra de 18 subjectes amb ruptura del lligament creuat i una mostra de 10 subjectes sans. Es van observar diferències als dos nivells, el qual suggereix que els subjectes amb ruptura al lligament creuat alteren les activacions musculars de la seva cama lesionada per tal d’estabilitzar l’articulació lesionada, en aquest cas el genoll. Per últim, en el tercer estudi, es van utilitzar les sinergies musculars junt amb un problema d’optimització de dues etapes per tal de predir les forces musculars i de contacte al genoll de manera fisiològicament consistent, alhora que es calibren els paràmetres musculars. En el nivell exterior de l’optimització, es calibren els paràmetres musculars, mentre que en el nivell interior, es calculen les activacions musculars amb els corresponents paràmetres musculars. Els resultats indiquen que un conjunt de paràmetres musculars pot predir les forces de contacte al genoll amb alta precisió quan es disposa de les forces experimentals de contacte al genoll durant el procés de calibratge. Aquest estudi presenta les diferències entre el cas en què s’utilitzen les forces experimentals de contacte al genoll per calibrar els paràmetres i quan no s’utilitzen. A més, suggereix que si s’utilitzessin captures biomecàniques de moviments on els músculs laterals tinguessin un rol més important que en la marxa, el calibratge dels paràmetres seria més acurat. Per tant, es podrien predir les forces de contacte al genoll amb més precisió quan no es disposa d’aquestes.

El primer objetivo de nuestro trabajo fue desarrollar un modelo de osteoporosis secundaria a ovariectomía en ratas Sprague-Dawley. El segundo objetivo consistió en analizar el efecto de los compuestos fenólicos: Naringenina, Eriocitrina y Citrolive®, sobre el citado modelo. Material y Métodos: Utilizamos 50 animales distribuidas en cinco Grupos (n=10): (I) Control; (II) Control ovariectomía; (III) Ovariectomía + Naringenina (1mg/kg día), (IV) Ovariectomía + Eriocitrina (1mg/kg día) y (V) Ovariectomía + Citrolive®. (1mg/kg día). La ovariectomía realizada a los Grupos (II, III, IV y V) fue bilateral y tras cuatro meses de tratamiento, los animales fueron sacrificados para extraer las muestras. Durante el experimento se pesó a los animales periódicamente y se les extrajo sangre para el estudio bioquímico. Realizamos las siguientes determinaciones: bioquímica general, distribución de la masa ósea y cuantificación de la densidad mineral mediante microtomografía computerizada, estudio anatomo-patológico del grosor de las trabéculas óseas y ionómico de los componentes químicos del hueso mediante espectrofotometría. Resultados: En el estudio bioquímico, los niveles séricos de calcio y fósforo se mantuvieron estables en todos los Grupos experimentales mientras que los niveles de fosfatasa alcalina total fueron superiores en el Grupo (III) Naringenina y con valores muy parecidos al Grupo (I) Control en el resto de Grupos tratados. No obstante, los resultados más relevantes fueron observados a nivel óseo. Así, tanto el grosor como el volumen de las trabéculas óseas de los animales tratados, eran mayores, que los de los animales ovariectomizados no tratados, Grupo (II). Además, los animales, de los tres Grupos tratados sufrieron menor pérdida de los minerales que conforman la matriz ósea que los del Grupo (II) según el estudio ionómico. Conclusiones: Consideramos, que la administración de dichos compuestos ha demostrado efectividad, aunque de grado variable, sobre el modelo de osteoporosis desarrollado. No obstante, son necesarios futuros estudios que permitan clarificar su mecanismo de acción y seguir avanzando en su posible utilización en clínica humana. / The first aim of this work was to develop an ovariectomized rat model of osteoporosis. The second objective was to analyse the effect of the phenolic compounds, Naringenia, Eriocitrin and Citrolive®, on that model. Materials and Methods: We used 50 animals distributed into 5 groups (n=10): (I) Control; (II) Ovariectomy control; (III) Ovariectomy + Naringenin (1mg/kg día), (IV) Ovariectomy + Eriocitrin (1mg/kg day) and (V) Ovariectomy + Citrolive® (1mg/kg day). Animals in groups (II, III, IV and V) were bilaterally ovareictomized. After 4 months of treatment, the animals were sacrificed to extract their femurs for analysis. Animal weight, general biochemistry, distribution of bone mass and quantification of mineral density by computerized microtomography, anatomical-pathological study of bone trabeculae and ionomic study of the chemical components of the bone by spectrophotometry, were carried out to determine the effects of the treatments on the animal model. Results: At the end of the experiment all the animals of the treated groups showed a delayed weight gain compared with the control group (I). In the biochemical study, the serum levels of calcium and phosphorus remained stable in all the experimental groups, while the total alkaline phosphate levels were highest in in group (III) Naringenina and lowest in control group (II) OVX. However, the most interesting results were observed at osseous level – both the thickness and volume of the trabeculae of the treated animals were greater than the corresponding measurements made in untreated animals that had been subjected to ovariectomy, group (II). In addition, the ionomic study showed that the animals of the three treated groups suffered lower loss of the minerals conforming the bone matrix of Group (II). Conclusion: We are of the opinion, therefore, that the administration of the mentioned compounds is effective, although to varying degrees, in the osteoporosis model developed. However, more studies are necessary to clarify their action mechanism before clinical application in humans can be considered.

Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain.

La respiration est une activité motrice autonome rythmique au cours de laquelle de nombreux muscles se contractent de manière coordonnée afin de produire des mouvements ventilatoires adaptés aux contraintes environnementales et aux exigences de l'organisme. Cette fonction vitale doit être fiable et adaptable à très court terme, c’est pourquoi elle est influencée, entre autres, par un grand nombre d’activités motrices. Par exemple, lors d’exercices physiques, le rythme respiratoire peut se coupler au rythme locomoteur. Les objectifs de ce travail doctoral sont centrés sur l’exploration des mécanismes neurogènes à la base du couplage entre ces deux fonctions motrices chez le rat nouveau-né. Pour une grande partie, cette étude a été réalisée sur préparation isolée in vitro de tronc cérébral-moelle épinière de rat nouveau-né (0 à 3 jours), ce modèle permettant de conserver dans leur intégrité les centres responsables des rythmes respiratoire et locomoteur. Compte tenu de l’accessibilité directe aux réseaux neuronaux, les mécanismes de couplage et d'entraînement respiratoire ont été abordés par des approches combinées électrophysiologique, neuroanatomique, pharmacologique et lésionnelle. Dans ce contexte, un des principaux résultats de ce travail doctoral est le rôle crucial joué par les informations sensorielles en provenance des membres antérieurs et postérieurs dans l'entraînement respiratoire observé lors de séquences locomotrices. Ainsi, les afférences proprioceptives spinales capables de réinitialiser et d'entraîner l’activité des centres respiratoires bulbaires via un relais pontique, établissent également des connexions sur l’ensemble des populations de motoneurones spinaux respiratoires phréniques, intercostaux et abdominaux. / Respiration is an autonomous rhythmic motor activity that requires the coordinated contractions of diverse muscles to produce ventilatory movements adapted to organismal needs. This crucial physiological function must be reliable and adaptable on a short-term basis, and requires coordianted movements with various other motor activities. For instance, respiratory rhythmicity becomes coupled to locomotion during physical exercise. My doctoral work aimed to explore the neurogenic mechanisms underlying the interactions between these two motor functions in the neonatal rat. This work was mainly conducted on isolated in vitro brain stem-spinal cord preparations of newborn rats (0-3 days), an experimental model that allows the maintenance of the still functional respiratory and locomotor CPGs in vitro. Due to the easy access to the neuronal networks in these preparations, locomotor-respiratory coupling and respiratory entrainment mechanisms were investigated by combined electrophysiological, neuroanatomical, pharmacological and lesional approaches. A major finding was the crucial played by sensory information from fore- and hindlimb in respiratory entrainment induced by locomotor rythmicity. Spinal sensory afferents can reset and entrain the activity of the medullary respiratory centres via a pontine relay, as well as making direct connections with the various spinal respiratory motoneuron (phrenic, intercostal and abdominal) populations.

This diploma thesis deals with the Achilles tendinopathy, and particularly with its etiopatogenetics. The theoretical part includes information about the Achilles tendon, tendinopathy of Achilles tendon and a summary of dysfunctions of the locomotor system. We assumed that the dysfunction of the locomotor system is the main etiopatogenetic factor of the Achilles tendinopathy, and that it results in changes of its position and loading. In the practical part we tried to reveal these dysfunctions by examination of seven patients, and to prove its main etiopatogenetic influence by a successfull therapy. The aim of the thesis was to point out the importance of the examination as well as the therapy of the locomotor systems function. Powered by TCPDF (www.tcpdf.org)

La locomotion implique l'activité coordonnée de réseaux d'interneurones spinaux inhibiteurs et excitateurs qui génèrent le rythme et le pattern de la décharge des motoneurones et de la contraction musculaire. La maturation de la transmission inhibitrice au niveau des motoneurones chez le rat se produit durant la période périnatale. Dans cette fenêtre temporelle, les projections provenant du tronc cérébral commencent à envahir l'élargissement lombaire de la moelle épinière. Nous avons étudié les effets du blocage de la mise en place des afférences supraspinales dans la moelle lombaire par transection complète de la moelle épinière (SCT) à la naissance (P0), sur l'expression des sous-unités des récepteurs GABAA et glycine (RcGABAA et RcGly) au niveau des motoneurones lombaires. Nous concluons en une plasticité différentielle des récepteurs de l'inhibition en réponse à une section spinale néonatale. La première étape de notre seconde étude était d'évaluer les modifications de la transmission synaptique inhibitrice sur des motoneurones lombaires innervant des muscles fléchisseurs et extenseurs après SCT complète chez des rats adultes. Une étude longitudinale a montré une évolution différentielle de l'expression des RcGly et des RcGABAA au cours des mois qui suivent la lésion mais qui est a peu près identique sur les Mns fléchisseurs et extenseurs. Nos résultats montrent que chez les rats avec SCT, l'entrainement permet d'acquérir une « locomotion spinale » qui résulte d'interactions dynamiques entre un programme moteur dans la moelle sous lésionnelle, et des feedback proprioceptifs. / Maturation of inhibitory postsynaptic transmission onto motoneurons in the rat occurs during the perinatal period, a time window during which pathways arising from the brainstem reach the lumbar enlargement of the spinal cord. There is a developmental switch in miniature IPSCs (mIPSCs) from predominantly long-duration GABAergic to short-duration glycinergic events. We investigated the effects of a complete neonatal [postnatal day 0 (P0)] spinal cord transection (SCT) on the expression of Glycine and GABAA receptor subunits (GlyR and GABAAR subunits) in lumbar motoneurons. In P7 animals with neonatal SCT (SCT-P7), the GlyR densities were unchanged compared with controls of the same age, while the developmental down regulation of GABAAR was prevented. After spinal cord injury, the disruption of flexion/extension and left-right alternations is largely attributed to a deterioration of the inhibitory circuitry below the lesion, but most of the cellular mechanisms are still unknown. Our aim of this was to measure the alteration of the GABA and glycinergic synaptic transmission on lumbar motoneurons (Mns) after spinal cord transection (SCT) in the adult rat, and evaluate the benefit of manual training and stepping recovery on the inhibitory networks. All in all our results show that, the presynaptic and postsynaptic components of the glycinergic synapses are relatively preserved on lumbar Mns. We developed a manual training procedure, based on daily alternate phases of imposed stepping and free walking in enriched environment. Pharmacological treatment with 5-HT2 receptor agonists allowed a standing recovery and alternate stepping.