L'amélioration de la vie des personnes en situation d'handicap est un défi majeur dans notre société. Dans le cas d'un handicap dû à des déficiences du système sensori-moteur, les solutions chirurgicales ou médicamenteuses peuvent rarement restaurer les fonctions altérées. Des solutions plus technologiques peuvent, dans certains cas, être utilisées afin de contourner les problématiques de dysfonctionnement du système nerveux. Une des solutions envisageables consiste à contrôler certaines fonctions par stimulation électrique fonctionnelle. Pour que cette stimulation soit efficace et se rapproche du contrôle naturel une approche intéressante consiste à utiliser les capteurs sensoriels naturels dans la boucle de contrôle du système. Dans le cadre de ce travail de thèse, nous nous intéressons aux systèmes d'acquisition électriques des signaux neurologiques provenant du système nerveux périphérique. L’idée est que les informations issues des fibres nerveuses afférentes obtenues à l’aide d’électrodes extra-neurales (ex. Cuff) pourraient permettre de « capter » l’information sensorielle provenant de plusieurs capteurs naturels sans être trop invasif.La principale difficulté de cette technique et de discriminer l'activité d'une fibre ou d’un groupe de fibres à partir du signal composite recueilli par l’électrode. Ce signal regroupe, en effet, l’information provenant d’un grand nombre de fibres afférentes et efférentes d’origine très différentes. Une des approches envisageables consiste à discriminer l’information des différentes fibres à partir de leurs caractéristiques physiologiques ou anatomiques. Les travaux présentés dans ce manuscrit cherchent à améliorer la sélectivité du recueil en fonction de la vitesse de propagation des différentes fibres. A noter qu’aucune solution réellement viable n’existe dans la littérature sur ce principe de sélectivité. Le premier objectif a donc été de prouver que dans un cas idéal (filtre parfait), il serait possible d’effectuer une discrimination efficace. Nos travaux sont basés sur des études temporelles, spatiales et spatio-temporelles afin d’évaluer les possibilités d'extraction de l'information utile à partir des potentiels extracellulaires simulés. Les simulations ont été effectuées à partir d'un modèle de système d'acquisition réaliste développé à partir des paramètres du modèle biophysiologique et du modèle d’électrode et du préamplificateur associé. Partant des résultats prometteurs obtenus dans un cas d’un filtre idéal, des implémentations de filtres IIR et FIR spatio-temporel du premier et second ordre ont été proposées. Les paramètres de stabilité des filtres proposés ont été étudiés et permettent d’envisager une implémentation physique efficace. / Improving the lives of people with disabilities is a major challenge in our society. In the case of a handicap due to deficiencies of the sensory-motor system, surgical or drug solutions can rarely restore the altered functions. More technological solutions may in some cases be used to bypass problematic malfunction of the nervous system. One solution is to control certain functions by functional electrical stimulation. For this to be effective stimulation and approaches the natural control an interesting approach is to use natural touch sensors in the system control loop. As part of this thesis, we focus on electrical systems acquisition neurological signals from the peripheral nervous system. The idea is that the information from the afferent nerve fibers obtained using extra-neural electrodes (eg. Cuff) could help to "capture" the sensory information from several sensors natural without being too invasive. The main difficulty of this technique and to discriminate the activity of a fiber or group of fibers from the composite signal received by the electrode. This signal includes, in fact, information from a large number of afferent and efferent very different origin. One possible approach is to discriminate the information of different fibers from their physiological and anatomical features. The work presented in this manuscript are looking to improve the selectivity of the collection based on the propagation speed of the different fibers. Note that no truly viable solution exists in the literature on this principle of selectivity. The first objective was therefore to prove that in an ideal case (ideal filter), it would be possible to make effective discrimination. Our work is based on studies of temporal, spatial and spatio-temporal order to assess the possibilities of extracting useful information from the simulated extracellular potentials. The simulations were performed from a realistic acquisition system model developed from the parameters of the model and biophysiological electrode model and associated preamplifier. Based on the promising results obtained in a case of an ideal filter, IIR filter implementations and spatiotemporal FIR of first and second order have been proposed. The proposed filter stability parameters have been studied and possible to envisage an effective physical implementation.

Bakgrund: Rehabiliteringen efter en rotatorkuffrupturoperation är oftast lång och följer olika faser med hänsyn till senans inläkning. Behandlingsresultatet är multifaktoriellt och det rekommenderas att rehabiliteringen individanpassas. För att följa och utvärdera rehabiliteringsprocessen behövs funktionella axeltester. I dagsläget saknas reliabla och validerade funktionella axeltester under rehabiliteringens tidigare faser. Syfte: Syftet med denna studie är att undersöka reliabiliteten hos två standardiserade armlyft, Aktivt armlyft i flexion och Aktivt armlyft i skapulaplanet, med statiskt kvarhåll i 90° under 30 sekunder, för vuxna individer som genomgått enrotatorkuffrupturoperation för cirka tre månader sedan. Metod: Datainsamlingen utfördes i tre steg, först utfördes en videoinspelning av de standardiserade armlyften av två fysioterapeuter. Därefter utfördes två bedömningstillfällen av två andra fysioterapeuter. Videoinspelningarna, armlyften och bedömningarna utfördes enligt standardiserade protokoll. Inter- och intrareliabilitetsbedömningarna baserades på videoinspelningarna där de två bedömarna graderade patienternas förmåga att utföra de två standardiserade armlyften utifrån utfallsmåtten ”Klarar” eller ”Klarar ej”. Överensstämmelsen analyserades i IBM SPSS med Cohens Kappa. Resultat: Åtta manliga studiedeltagare i åldrarna 49–71 år (medelålder 59,4 år) deltog. Videoinspelningarna utfördes i genomsnitt 15,25 (±3,9) veckor efter operation. Den andra bedömningen genomfördes i genomsnitt 9 (±3,1) dagar efterförsta bedömningen. Resultatet visade att interbedömarreliabiliteten var ”God”(k=0,71) till ”Utmärkt” (k=1,00) och intrabedömareliabiliteten var ”Utmärkt”(k=1,00). Slutsats: Denna studie fann att inter- och intrabedömarreliabilitet var ”God” till”Utmärkt” gällande de två standardiserade armlyften. Resultatet bör tolkas med försiktighet på grund av det begränsade deltagarantalet och ingen säker slutsats kandras. Ytterligare forskning behövs för att fastställa klinisk betydelse. / Background: Rehabilitation after rotator cuff tear surgery is often long and follows different phases with consideration for tendon healing. The treatment result is multifactorial, and the rehabilitation is recommended to be individualized.vFunctional shoulder tests are of value and evaluate the rehabilitation process. Currently, reliable and validated functional shoulder tests are lacking during the earlier phases of rehabilitation. Purpose: The purpose of this study is to investigate the reliability of two standardized arm lifts, Active shoulder flexion and Active shoulder scaption, with astatic hold at 90° for 30 seconds, three months post-surgery. Method: Data collection was conducted in three steps. Starting with videorecordings of the standardized arm lifts by two physiotherapists. Followed by two assessment sessions with approximately one week apart, by two other physiotherapists. The video recordings, arm lifts, and assessments were performed according to standardized protocols. Inter- and intrarater reliability assessments were based on the video recordings. The examiners graded the patient’s ability to perform the two functional shoulder tests based on the outcomes "Approved" or "Non-approved". The agreement was calculated with IBM SPSS using Cohen's Kappa. Results: Eight men were included, 49-71 years (mean age 59,4 years). The videorecordings and the first evaluation were performed in mean 15,3 (±3,9) weeks postsurgery. The second evaluation was performed in mean 9,4 (±3,1) days after the first evaluation. The results showed that the interrater-reliability was “Good” (k=0,71) to“Excellent” (k=1,00), and the intrarater-reliability was “Excellent” (k=1,00). Conclusion: This study found that the inter- and intrarater reliability for the two standardized arm lifts were good to excellent. The limited number of participants requires caution with the interpretation of the results and no definitive conclusion can be drawn. Further research is needed to establish any clinical significance.

INTRODUCÃO: A acurácia da ressonância magnetica (RM) para a detecção de rotura do subescapular apresenta ampla variação na literatura. Existem poucos estudos prospectivos e grande variação metodológica. Acredita-se que estas roturas sejam mais dificilmente diagnosticadas do que as posterossuperiores. O tendão do subescapular apresenta importância na biomecânica no ombro e sua rotura leva a prejuízo funcional. Uma ferramenta diagnóstica de boa acurácia é fundamental na prática clínica, influenciando o prognóstico e o planejamento cirúrgico. O objetivo deste estudo foi avaliar a validade da RM pre-operatória na identificação das roturas do subescapular, comparando os achados de imagem com os dados intra-operatórios de cirurgia artroscó pica. Como objetivo secundário, avaliamos a confiabilidade do método, por meio da concordância interobservador e intraobservador. MÈTODOS: Realizamos um estudo de acurácia diagnóstica comparando os achados da RM (teste índice) com os da artroscopia (teste de referência), em uma coorte prospectiva. Foram incluídos pacientes submetidos a artroscopia para tratamento de roturas do manguito rotador que houvessem realizado RM de alto campo magnético, sem uso de contraste. Foram excluídos casos de manipulacão cirúrgica pregressa no ombro, exames com artefatos de movimentação, indicação cirurgia por via aberta e intervalo entre a RM e procedimento cirúrgico superior a um ano. As imagens foram avaliadas por um cirurgião de ombro e dois radiologistas musculoesqueleticos, de maneira independente e cegos em relacão aos resultados da artroscopia, sendo reavaliadas apos 3 meses pelo cirurgião. Calculamos a validade (sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia) e confiabilidade (concordancia inter e intraobservador) da RM em detectar roturas do subescapular. RESULTADOS: Avaliamos 200 ombros. A incidencia de roturas do subescapular foi de 69,5% (41,5% parciais e 28,0% transfixantes). O cirurgião de ombro apresentou sensibilidade de 51,1 a 59,0% e especificidade de 91,7% a 94,4%. Os radiologistas, 83,5 a 87,1% de sensibilidade e 41 a 45,9% de especificidade. A acura?cia variou de 60,5 a 73,0%. Os valores médios de sensibilidade, especificidade e acurácia foram 70,2%, 61,9% e 67,6%, respectivamente. A concordância interobservador foi moderada para a deteccao de roturas do subescapular (coeficiente kappa 0,463, IC 95% 0,383- 0,534, p < 0,001), assim como a intraobservador (coeficiente kappa 0,546, IC 95% 0,430-0,662, p < 0,001). Os pacientes com rotura do subescapular apresentaram maior incidencia de rotura e instabilidade do bíceps, maior degeneração gordurosa do subescapular e média de idade superior. As demais variáveis nao apresentaram diferenças estatisticamente significantes. CONCLUSAO: A RM de alto campo magneético sem contraste apresentou valores médios de sensibilidade, especificidade e acurácia de 70,2%, 61,9% e 67,6%, respectivamente. A sensibilidade foi superior nos radiologistas enquanto a especificidade no cirurgião de ombro. A concordância interobservador e intraobservador foi moderada / INTRODUCTION: The accuracy of magnetic resonance imaging (MRI) for the detection of subscapularis tear presents wide variation in the literature. There are few prospective studies and great methodological variation. It is believed that these tears are more difficult to diagnose than the posterosuperiores rotator cuff injuries. The subscapularis tendon has importance in the biomechanics in the shoulder and its rupture leads to functional impairment. A diagnostic tool of good accuracy is fundamental in clinical practice, influencing prognosis and surgical planning. The aim of this study was to evaluate the validity of preoperative MRI in the identification of the subscapularis tears, comparing the imaging findings with the intraoperative data of arthroscopic surgery. As a secondary objective, we evaluated the reliability of the method through interobserver and intraobserver agreement. METHODS: We performed a diagnostic accuracy study comparing MRI findings (index test) with those of arthroscopy (reference test), in a prospective cohort. We included patients submitted to arthroscopy for the treatment of rotator cuff tears that had undergone high magnetic field MRI without using contrast. Cases of previous surgical manipulation in the shoulder, exams with moving artifacts, indication for open surgery and interval between MRI and surgical procedure of more than one year were excluded. The images were evaluated by a shoulder surgeon and two musculoskeletal radiologists, independently and blinded to the results of arthroscopy, being reassessed after 3 months by the surgeon. We calculated the validity (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) and reliability (inter- and intraobserver agreement) of MR in detecting subscapularis tears. RESULTS: We evaluated 200 shoulders. The incidence of subscapularis tears was 69.5% (41.5% partial and 28.0% transfixing). The shoulder surgeon showed sensitivity from 51.1 to 59.0% and specificity from 91.7% to 94.4%. The radiologists, 83.5 to 87.1% of sensitivity and 41 to 45.9% of specificity. Accuracy ranged from 60.5 to 73.0%. The mean values of sensitivity, specificity and accuracy were 70.2%, 61.9% and 67.6%, respectively. Interobserver agreement was moderate for the detection of subscapular tears (kappa coefficient 0.463, 95% CI 0.383-0.534, p < 0.001), as well as intraobserver agreement (kappa coefficient 0.546, 95% CI 0.430-0.662, p < 0.001). Patients with subscapular rupture had a higher incidence of biceps rupture and instability, greater fat subscapular degeneration, and higher mean age. The other variables did not present statistically significant differences. CONCLUSION: MRI of high magnetic field without contrast showed mean values of sensitivity, specificity and accuracy of 70.2%, 61.9% and 67.6%, respectively. Sensitivity was higher in radiologists while specificity in the shoulder surgeon. Interobserver and intraobserver agreement was moderate

INTRODUCÃO: A acurácia da ressonância magnetica (RM) para a detecção de rotura do subescapular apresenta ampla variação na literatura. Existem poucos estudos prospectivos e grande variação metodológica. Acredita-se que estas roturas sejam mais dificilmente diagnosticadas do que as posterossuperiores. O tendão do subescapular apresenta importância na biomecânica no ombro e sua rotura leva a prejuízo funcional. Uma ferramenta diagnóstica de boa acurácia é fundamental na prática clínica, influenciando o prognóstico e o planejamento cirúrgico. O objetivo deste estudo foi avaliar a validade da RM pre-operatória na identificação das roturas do subescapular, comparando os achados de imagem com os dados intra-operatórios de cirurgia artroscó pica. Como objetivo secundário, avaliamos a confiabilidade do método, por meio da concordância interobservador e intraobservador. MÈTODOS: Realizamos um estudo de acurácia diagnóstica comparando os achados da RM (teste índice) com os da artroscopia (teste de referência), em uma coorte prospectiva. Foram incluídos pacientes submetidos a artroscopia para tratamento de roturas do manguito rotador que houvessem realizado RM de alto campo magnético, sem uso de contraste. Foram excluídos casos de manipulacão cirúrgica pregressa no ombro, exames com artefatos de movimentação, indicação cirurgia por via aberta e intervalo entre a RM e procedimento cirúrgico superior a um ano. As imagens foram avaliadas por um cirurgião de ombro e dois radiologistas musculoesqueleticos, de maneira independente e cegos em relacão aos resultados da artroscopia, sendo reavaliadas apos 3 meses pelo cirurgião. Calculamos a validade (sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia) e confiabilidade (concordancia inter e intraobservador) da RM em detectar roturas do subescapular. RESULTADOS: Avaliamos 200 ombros. A incidencia de roturas do subescapular foi de 69,5% (41,5% parciais e 28,0% transfixantes). O cirurgião de ombro apresentou sensibilidade de 51,1 a 59,0% e especificidade de 91,7% a 94,4%. Os radiologistas, 83,5 a 87,1% de sensibilidade e 41 a 45,9% de especificidade. A acura?cia variou de 60,5 a 73,0%. Os valores médios de sensibilidade, especificidade e acurácia foram 70,2%, 61,9% e 67,6%, respectivamente. A concordância interobservador foi moderada para a deteccao de roturas do subescapular (coeficiente kappa 0,463, IC 95% 0,383- 0,534, p < 0,001), assim como a intraobservador (coeficiente kappa 0,546, IC 95% 0,430-0,662, p < 0,001). Os pacientes com rotura do subescapular apresentaram maior incidencia de rotura e instabilidade do bíceps, maior degeneração gordurosa do subescapular e média de idade superior. As demais variáveis nao apresentaram diferenças estatisticamente significantes. CONCLUSAO: A RM de alto campo magneético sem contraste apresentou valores médios de sensibilidade, especificidade e acurácia de 70,2%, 61,9% e 67,6%, respectivamente. A sensibilidade foi superior nos radiologistas enquanto a especificidade no cirurgião de ombro. A concordância interobservador e intraobservador foi moderada / INTRODUCTION: The accuracy of magnetic resonance imaging (MRI) for the detection of subscapularis tear presents wide variation in the literature. There are few prospective studies and great methodological variation. It is believed that these tears are more difficult to diagnose than the posterosuperiores rotator cuff injuries. The subscapularis tendon has importance in the biomechanics in the shoulder and its rupture leads to functional impairment. A diagnostic tool of good accuracy is fundamental in clinical practice, influencing prognosis and surgical planning. The aim of this study was to evaluate the validity of preoperative MRI in the identification of the subscapularis tears, comparing the imaging findings with the intraoperative data of arthroscopic surgery. As a secondary objective, we evaluated the reliability of the method through interobserver and intraobserver agreement. METHODS: We performed a diagnostic accuracy study comparing MRI findings (index test) with those of arthroscopy (reference test), in a prospective cohort. We included patients submitted to arthroscopy for the treatment of rotator cuff tears that had undergone high magnetic field MRI without using contrast. Cases of previous surgical manipulation in the shoulder, exams with moving artifacts, indication for open surgery and interval between MRI and surgical procedure of more than one year were excluded. The images were evaluated by a shoulder surgeon and two musculoskeletal radiologists, independently and blinded to the results of arthroscopy, being reassessed after 3 months by the surgeon. We calculated the validity (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) and reliability (inter- and intraobserver agreement) of MR in detecting subscapularis tears. RESULTS: We evaluated 200 shoulders. The incidence of subscapularis tears was 69.5% (41.5% partial and 28.0% transfixing). The shoulder surgeon showed sensitivity from 51.1 to 59.0% and specificity from 91.7% to 94.4%. The radiologists, 83.5 to 87.1% of sensitivity and 41 to 45.9% of specificity. Accuracy ranged from 60.5 to 73.0%. The mean values of sensitivity, specificity and accuracy were 70.2%, 61.9% and 67.6%, respectively. Interobserver agreement was moderate for the detection of subscapular tears (kappa coefficient 0.463, 95% CI 0.383-0.534, p < 0.001), as well as intraobserver agreement (kappa coefficient 0.546, 95% CI 0.430-0.662, p < 0.001). Patients with subscapular rupture had a higher incidence of biceps rupture and instability, greater fat subscapular degeneration, and higher mean age. The other variables did not present statistically significant differences. CONCLUSION: MRI of high magnetic field without contrast showed mean values of sensitivity, specificity and accuracy of 70.2%, 61.9% and 67.6%, respectively. Sensitivity was higher in radiologists while specificity in the shoulder surgeon. Interobserver and intraobserver agreement was moderate

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2005 xiii, 70 leaves ; 30 cm / Although studies of manipulation-induced peripheral changes in the muscles have been done, inconsistencies noted by the author’s call for further investigation into the reflex effects of manipulation. Additionally, according to the literature, no effective treatment protocol for the painful shoulder has been found. Therefore this research aimed at addressing these discrepancies by quantifying the immediate effect of cervical spine manipulation in terms of peak torque on rotator cuff musculature in asymptomatic patients with both a cervical spine dysfunction and without. And thus by investigating cervical manipulation to the C4-C7 spinal segment, as a possible added intervention for improving rotator cuff muscle peak torque, a more efficient and effective management protocol for the painful shoulder could be attained. Thus the aims for this study included: 1) To evaluate whether manipulation has an effect on rotator cuff peak torque or not, utilizing the Cybex Orthotron II Isokinetic Rehabilitation System; 2) To ascertain whether manipulation of the specific levels has an effect on the rotator cuff peak torque or not and 3) To ascertain whether the presence or absence

The purpose of the study was to investigate the static and dynamic architecture of supraspinatus throughout its volume in the normal and pathological state. The architecture was first investigated in cadaveric specimens free of any tendon pathology. Using a serial dissection and digitization method tailored for supraspinatus, the musculotendinous architecture was modeled in situ. The 3D model reconstructed in Autodesk MayaTM allowed for visualization and quantification of the fiber bundle architecture i.e. fiber bundle length (FBL), pennation angle (PA), muscle volume (MV) and tendon dimensions. Based on attachment sites and architectural parameters, the supraspinatus was found to have two architecturally distinct regions, anterior and posterior, each with three subdivisions. The findings from the cadaveric investigation served as a map and platform for the development of an ultrasound (US) protocol that allowed for the dynamic fiber bundle architecture to be quantified in vivo in normal subjects and subjects with a full-thickness supraspinatus tendon tear. The architecture was studied in the relaxed state and in three contracted states (60º abduction with either neutral rotation, 80º external rotation, or 80º internal rotation). The dynamic changes in the architecture within the distinct regions of the muscle were not uniform and varied as a function of joint position. Mean FBL in the anterior region shortened significantly with contraction (p<0.05) but not in the posterior. In the anterior region, mean PA was significantly smaller in the middle part compared to the deep (p<0.05). Comparison of the normal and pathological muscle found large differences in the percentage change of FBL and PA with contraction. The architectural parameter that showed the largest changes with tendon pathology was PA. In sum, the results showed that the static and dynamic fiber bundle architecture of supraspinatus is heterogeneous throughout the muscle volume and may influence tendon stresses. The architectural data collected in this study and the 3D muscle model can be used to develop future contractile models. The US protocol may serve as an assessment tool to predict the functional outcome of rehabilitative exercises and surgery.

Currently there does not exist a type of peripheral nerve interface that adequately combines spatial selectivity, spatial coverage and low invasiveness. In order to address this lack, we investigated the application of bioelectric source localization algorithms, adapted from electroencephalography/magnetoencephalography, to recordings from a 56-contact “matrix” nerve cuff electrode. If successful, this strategy would enable us to improve current neuroprostheses and conduct more detailed investigations of neural control systems. Using forward field similarities, we first developed a method to reduce the number of unnecessary variables in the inverse problem, and in doing so obtained an upper bound on the spatial resolution. Next, a simulation study of the peripheral nerve source localization problem revealed that the method is unlikely to work unless noise is very low and a very accurate model of the nerve is available. Under more realistic conditions, the method had localization errors in the 140 μm-180 μm range, high numbers of spurious pathways, and low resolution. On the other hand, the simulations also showed that imposing physiologically meaningful constraints on the solution can reduce the number of spurious pathways. Both the influence of the constraints and the importance of the model accuracy were validated experimentally using recordings from rat sciatic nerves. Unfortunately, neither idealized models nor models based on nerve sample cross-sections were sufficiently accurate to allow reliable identification of the branches stimulated during the experiments. To overcome this problem, an experimental leadfield was constructed using training data, thereby eliminating the dependence on anatomical models. This new strategy was successful in identifying single-branch cases, but not multi-branches ones. Lastly, an examination of the information contained in the matrix cuff recordings was performed in comparison to a single-ring configuration of contacts. The matrix cuff was able to achieve better fascicle discrimination due to its ability to select among the most informative locations around the nerve. These findings suggest that nerve cuff-based neuroprosthetic applications would benefit from implanting devices with a large number of contacts, then performing a contact selection procedure. Conditions that must be met before source localization approaches can be applied in practice to peripheral nerves were also discussed.

Thesis questions: • Is the glutaminergic system altered in rotator cuff tendinopathy? • Is the glutaminergic system altered by common treatments? • Are glutaminergic changes related to pain symptoms? • What are the effects of glutamate and glutamate receptor modulation on tendon derived cells? Summary answers: • The glutaminergic system is altered in rotator cuff tendinopathy • Changes within this system are seen after common treatments • Specific glutaminergic changes are associated with the resolution of pain following shoulder surgery but do not predict the severity of pain symptoms • Glutamate has significant effects on tendon derived cells. What is known: It is known that extracellular glutamate concentrations are increased in both Achilles and patellar tendinopathy. It has also been previously shown that the glutamate receptors NMDAR1 and mGluR5 are upregulated in patellar tendinopathy. What this thesis adds: This thesis has shown for the first time that glutamate and NMDAR1 are increased in rotator cuff tendinopathy. Increases in cell proliferation, vascularity and HIF1α are seen after surgical rotator cuff repair and these features are not seen after glucocorticoid injection. There are significant differences between painful and pain-free rotator cuff tendons in terms of glutamate receptor expression (KA1, mGluR7 and mGluR2) and inflammatory cell numbers (CD45 and CD206). Exposure to 1.875mM glutamate for 72 hours results in reduced cell viability, decreased collagen (COL1A1 and COL3A1) and increased aggrecan gene expression; NMDAR antagonism with MK-801 attenuates the deleterious effect on cell viability but had no effect on the changes in matrix gene expression. Bias, confounding and other reasons for caution: The observational histological work was limited by the control tissue. Some control tissue was not age matched, while some of the pain-free control tendons were post-surgical intervention. Confounding factors include tendon structure, length of symptoms and previous treatments. Caution must be applied when discussing the in vivo implications of the in vitro work.

Les tendinopathies sont la première cause de maladie professionnelle en France. Elles sont devenues une préoccupation majeure de santé publique. Cependant, leurs mécanismes physiopathologiques restent encore mal définis. Au cours de cette thèse, nous nous sommes intéressés aux phases précoces de la tendinopathie engendrées par une sur-utilisation du tendon supra-épineux (tSE) de la coiffe de rotateurs de l’épaule chez le rat. Nous avons tenté de comprendre les mécanismes à l’origine de cette pathologie afin de pouvoir agir et la traiter en amont de l’apparition des symptômes.Nous montrons que le profil d’évolution moléculaire des collagènes, des protéoglycanes et des glycosaminoglycanes (GAGs) associé aux phases précoces de la sur-utilisation, témoigne d’un profond remaniement matriciel et d’une différenciation chondroïde des fibroblastes tendineux. Nous avons identifié les métalloprotéinases (MMPs) majeures et leurs inhibiteurs (TIMPs) susceptibles d’être impliqués dans ce remaniement. Nos résultats suggèrent que le mécanisme lésionnel initial et les changements matriciels observés sont dus à un processus induit par des médiateurs locaux libérés par les ténocytes et non à une réaction inflammatoire. Enfin, nous avons cherché à établir une corrélation entre les changements moléculaires observés et le degré de sévérité d’une tendinopathie diagnostiquée chez l’Homme. Nous avons montré, sur des échantillons de tendon patellaire humain une relation entre la quantité des GAGs et le score (VISA score) reflétant le degré pathologique du tendon.Cette étude nous a donc permis d’améliorer nos connaissances des phases précoces du processus d’altération du tSE. Cependant, d’importants efforts restent néanmoins à accomplir dans la caractérisation de la pathogenèse précoce notamment pour préciser le contexte biomécanique qui la génère. / Tendinopathies are the first cause of professional diseases in France. They are a major public health concern. However, their physiopathological mechanisms remain poorly understood. This project aimed at investigating the early stages of supraspinatus tendinopathy caused by overuse. Using a rat animal model, we attempted to understand the mechanisms behind this disease in order to act and treat the symptoms upstream of their onset.We have shown that the molecular changes of collagens, proteoglycans and glycosaminoglycans (GAGs) associated with the early events of overuse attest a major matrix remodeling and chondrogenic differentiation of tendon cells. We identified the main metalloproteinases (MMPs) and their inhibitors (TIMPs) that may be involved in this remodeling. Our results further suggest that the initial mechanisms linked to the observed matrix changes are due to local mediators release by tenocytes rather than an inflammatory process. Finally, we attempted to correlate molecular changes observed during overuse with the severity of the tendinopathy diagnosed in humans. We have shown a relationship between the amount of GAGs and the pathological score (VISA score) on human patellar tendons.This study improved our knowledge of the early pathological events of the supraspinatus tendon. However, more remains to be done for characterizing the early stages of tendinopathy especially to clarify the biomechanical context up-stream.

INTRODUÇÃO: Na patogênese da rotura do manguito rotador, diminuição da síntese e aumento da degradação das fibras colágenas são encontradas, associadas ao aumento da atividade das metaloproteinases da matriz 1 e 3 (MMP-1 e MMP-3). Há evidências que fatores genéticos estão envolvidos na produção das metaloproteinases e na etiologia da rotura do manguito rotador. O objetivo deste estudo foi avaliar a associação entre o polimorfismo genético das MMP-1 e MMP-3 com a rotura de espessura completa do manguito rotador. Como objetivos secundários, tivemos avaliar a correlação dos haplótipos da MMP-1 e MMP-3 com a rotura de espessura completa do manguito rotador e comparar se indíviduos com rotura transfixante do manguito rotador têm maior proporção de familiares com a mesma doença, em relação aos indíviduos controles. MÉTODOS: Avaliamos 64 pacientes com rotura transfixante do manguito rotador e 64 controles assintomáticos. Foram incluídos apenas pacientes com idade inferior a 65 anos e rotura de espessura completa não traumática. A rotura ou integridade do manguito rotador foi avaliada por ressonância magnética ou ultrassonografia em todos indivíduos. Os pacientes e os controles foram pareados por idade. O ácido desoxirribonucleico (DNA) dos voluntários foi obtido a partir de células epiteliais da mucosa bucal. Os genótipos das MMP-1 e MMP-3 foram determinados utilizando as técnicas de Reação em Cadeia de Polimerase (PCR) e Polimorfismo no Comprimento de Fragmentos de Restrição (RFLP). RESULTADOS: Observamos uma presença de 77% do alelo 1G e 64% do genótipo 1G/1G no grupo controle. Os pacientes com rotura transfixante do manguito rotador apresentaram uma taxa de 48% do alelo 2G e 73% de genótipos 1G/2G ou 2G/2G (p < 0,001). Indivíduos com genótipo 1G/2G e 2G/2G tiveram maior chance de ter uma rotura do manguito rotador: razão de chances (RC) igual a 4,8 (Intervalo de confiança de 95% [IC 95%] 2,1 a 11,0) e 5,2 (IC 95% 1,8 a 14,9), respectivamente. Também observamos uma distribuição significativamente diferente nos alelos e genótipos da MMP-3 (p = 0,045, p = 0,021, respectivamente) entre os casos e controles. Indivíduos com genótipo 5A/5A tiveram maior chance de apresentarem uma rotura do manguito rotador (RC 5,5; IC 95% 1,4 a 20,9). Indíviduos com haplótipo 2G/5A tiveram maior possibilidade de ter uma rotura do manguito rotador, este haplótipo foi encontrado em 42 de 64 pacientes (66%) e em 17 de 64 controles (27%), com razão de chances de 5,3 (IC 95% 2,5 a 11,3). Pacientes com rotura do manguito rotador relataram, em maior número (19 de 64 pacientes, 30%), a existência de familiares que realizaram tratamento para rotura do manguito rotador em relação aos pacientes controles (quatro de 64 pacientes, 6%; p = 0,001). CONCLUSÃO: O polimorfismo genético das MMP-1 e MMP-3 foi associado à rotura do manguito rotador / INTRODUCTION: In the pathogenesis of rotator cuff tear, decreased synthesis and increased degradation of collagen fibers are found, associated with an increase in activity of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3). There is evidence that genetic factors may be involved in metalloproteinase production and the etiology of rotator cuff tear. The aim of this study was to evaluate the association between the genetic polymorphism of MMP-1 and MMP-3 and full-thickness rotator cuff tear. As secondary aims, we measured the correlation of MMP-1 and MMP-3 haplotypes with full-thickness rotator cuff tears and compared if individuals with full-thickness rotator cuff tears have a higher proportion of relatives with the same disease than the control subjects. METHODS: We evaluated 64 patients with full-thickness rotator cuff tear and 64 asymptomatic controls. Patients aged below 65 years, with non-traumatic full thickness tears, were included. The rotator cuff tear or integrity was evaluated by magnetic resonance or ultrasound in all individuals. The patients and controls were paired by age. The deoxyribonucleic acid (DNA) of the volunteers was obtained from oral mucosa epithelial cells. MMP-1 and MMP-3 genotypes were determined using the Polimerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) assays. RESULTS: We observed a 77% presence of allele 1G and 64% of genotypes 1G/1G in the control group. The patients with full-thickness rotator cuff tear presented 48% of allele 2G and 73% of genotypes 1G/2G or 2G/2G (p < 0.001). Individuals with genotypes 1G/2G and 2G/2G were more likely to have a rotator cuff tear: odds ratio equal to 4.8 (95% confidence interval [95% CI] 2.1 to 11.0) and 5.2 (95% CI 1.8 to 14.9), respectively. We also observed a significantly different distribution in the alleles and genotypes of MMP-3 (p = 0.045, p = 0.021, respectively) among the cases and controls. Individuals with the 5A/5A genotype were more likely to have a rotator cuff tear (OR 5.5; 95% CI 1.4 to 20.9). Individuals with the haplotype 2G/5A were more likely to have rotator cuff tears develop, this haplotype was found in 42 of 64 patients (66%) and in 17 of 64 controls (27%) with odds ratio 5.3 (95% CI 2.5 to 11.3). Patients with rotator cuff tears reported, in higher number (19 of 64 patients, 30%), the existence of relatives who previously had treatment for rotator cuff tears compared to control patients (four of 64 patients, 6%; p = 0,001). CONCLUSION: The genetic polymorphism of MMP-1 and MMP-3 was associated with rotator cuff tear