Après un traumatisme de la moelle épinière (TM), l’ischémieest un facteur d’aggravation des lésions. Cette ischémie peut être aggravée par l’augmentation depression du liquide cérébro-spinal (LCS) par le biais d’un effet tamponnade. Or chez l’homme,après un TM avec préservation de l’intégrité de la dure-mère, la pression de LCS augmentesignificativement. On suppose donc que le maintien d’une pression de LCS à des valeursphysiologique pourrait être une méthode de limitation de l’ischémie post-traumatique et doncd’amélioration du pronostic fonctionnel. Afin de pouvoir réaliser une étude expérimentale de cesphénomènes, nous avons consacré la première partie expérimentale de cette thèse à la mise au pointd’un modèle de TM à dure-mère intacte chez le rat permettant la mesure simultanée de la pressionde LCS et de la perfusion médullaire. Nous avons confirmé expérimentalement que la pression deLCS augmente après TM. Dans la seconde partie expérimentale, nous avons mis au point unetechnique expérimentale de quantification spatiale et temporelle de la perfusion médullaire grâce àl’échographie de contraste. Cette technique permettait aussi un suivi en temps réel de l’évolution dusaignement intra-parenchymateux induit par le TM. Dans la troisième partie expérimentale, nousavons utilisé notre modèle couplé avec l’échographie de contraste et le laser Doppler pour évaluerles effets de la noradrénaline injectée à la phase aigüe d’un TM sur la perfusion médullaire et lesaignement intra-parenchymateux. Nous avons montré que la noradrénaline augmentait trèslégèrement le flux sanguin superficiel mais pas le flux sanguin profond et qu’elle augmentait lataille du saignement. / After spinal cord injury (SCI), ischaemia aggravates lesions.Increase in cerebrospinal fluid (CSF) pressure can worsens ischaemia through a tamponnade effect.In humans, it has been shown that after SCI with intact dura mater, CSF pressure significantlyincreases. Therefore, preserving CSF pressure within a physiological range may limit post-traumaischaemia and improve neurological outcome. In order to experimentally study these phenomenon,we have dedicated the first part of that work to create a model of SCI in rats preserving dura’sintegrity and allowing simultaneous measurement of spinal cord blood flow (SCBF) and CSFpressure. We have confirmed that CSF pressure increases after SCI with intact dura. In the secondexperimental part, we have developed a technique allowing to perform spatial and temporalmeasurement of SCBF thanks to contrast enhanced ultrasonography (CEU). Moreover, thistechnique allows real-time measurement of the size of the parenchymal hemorrhage. In the thirdexperimental part, we have used our experimental model in association with CEU and LaserDoppler to assess the effects of early injection of norepinephrine on SCBF and parenchymalhemorrhage. We found that norepinephrine induces a slight increase in superficial SCBF while itdoesn’t modify deep SCBF and significantly increases the size of parenchymal hemorrhage.

Medir a espessura da parede vesical (EPV) através da ultrassonografia, correlacioná-la com os parâmetros urodinâmicos e avaliar o papel destes parâmetros para lesão do trato urinário superior. Avaliar também o papel das alterações da forma da bexiga nos resultados de injeção de toxina botulínica tipo-A (BTX-A) no detrusor em pacientes com lesão medular traumática (LMT). Trata-se de dois estudos. O primeiro é um estudo transversal de 272 pacientes com LMT submetidos à ultrassonografia renal e de bexiga e estudo urodinâmico. A parede anterior da bexiga foi medida e comparada com os dados urodinâmicos. A cistografia foi realizada em 57 pacientes. O segundo foi um estudo prospectivo avaliando os resultados da injeção de BTX-A no detrusor em 27 pacientes considerando os achados urodinâmicos (pré e pós procedimento) e as deformidades da bexiga (cistografia). A média da EPV foi de 3,94 mm e foi estatisticamente maior em pacientes com hiperatividade detrusora neurogênica associada à dissinergia vesicoesfincteriana (HDN/DVE), em comparação com aqueles sem DVE (p<0,001). Essa média também foi maior em pacientes com complacência < 20 mL/cmH2O, comparada aos pacientes com complacência &#8805; 20 mL/cmH2O (p<0,001). A média da pressão detrusora máxima (Pdet Max) foi estatisticamente maior nos pacientes com refluxo vesicoureteral (RVU) em comparação com aqueles sem RVU (100,7 vs 61,2 cmH2O respectivamente, p=0,022). Pacientes com complacência < 20 mL/cmH2O apresentaram prevalência de hidronefrose 4,2 vezes maior, comparada aos pacientes com complacência &#8805; 20 mL/cmH2O. Não houve associação estatística entre EPV e hidronefrose ou RVU. Vinte e sete pacientes foram submetidos à injeção de BTX-A no detrusor. A média de tempo de continência urinária foi de 8 meses. Nove pacientes (33,3%) tinham forma vesical alterada e 8 casos (29,6%) tinham divertículos. A capacidade cistométrica máxima, Pdet max, volume reflexo e complacência não apresentaram diferença significativa na presença de divertículos ou alteração da forma. O aumento da EPV está associado à complacência < 20 mL/cmH2O e HDN/DVE em pacientes com LMT. No entanto, não houve relação entre a EPV e hidronefrose ou RVU. Baixa complacência e HDN/DVE são os principais fatores de risco para dano ao trato urinário superior. A presença de divertículos ou alteração da forma vesical não influenciou nos resultados após injeção de BTX-A no detrusor. / To investigate the ultrasonographic bladder wall thickness (BWT), urodynamic parameters and evaluate the role of such measurements for the upper and lower urinary tract deterioration and also assess the role of changes in bladder shape in the outcome of botulinum toxin type A (BTX-A) into the detrusor in patients with spinal cord injury (SCI). There are two studies. First study was a cross-sectional study involving two hundred and seventy two patients with SCI who underwent renal and bladder ultrasonography and urodynamic evaluation. The anterior bladder wall was measured and compared to urodynamic data. Cystography was done in 57 patients. The second was a prospective study about injection of BTX-A into the detrusor performed in 27 patients considering urodynamic parameters and cystography findings. Mean BWT was 3.94 mm. BWT was statistically higher in patients with neurogenic detrusor overactivity associated to detrusor sphincter dyssynergia (NDO/DSD) and in those with compliance < 20 mL/cmH2O. Patients with low compliance (< 20 mL/cmH2O), had 4.2 times higher prevalence of hydronephrosis, compared to patients with compliance &#8805; 20 mL/cmH2O. Mean of Pdet max was statistically higher in patients with vesicoureteral reflux (VUR) compared to those without (100.7 vs 61.2 cmH2O respectively, p=0.022). There was no statistical association between BWT and hydronephrosis or VUR. Twenty seven patients underwent injection of BTX-A into the detrusor. The average time of urinary continence was 8 months. Nine patients (33.3%) had altered bladder shape and 8 cases (29.6%) had diverticula. The maximum cystometric capacity, NDO, reflex volume and compliance showed no statistically significant difference in the presence of diverticula or altered bladder shape. Increased BWT is associated with low compliance and NDO/DSD in patients with SCI. However, there was no relationship between BWT and hydronephrosis or VUR. Low compliance and NDO/DSD are the main risk factors for the upper urinary tract damage. The presence of diverticula or changes in bladder shape did not influence the results after injection of BTX-A into the detrusor.

Les lésions spinales conduisent à des altérations majeures des fonctions sensorimotrices. Les récupérations fonctionnelles consécutives à ces atteintes sont très limitées, notamment en raison des capacités réduites de réparation des tissus endommagés dans le SNC. En outre, ces récupérations dépendent notamment de plusieurs processus cellulaires tels que l'activation astrogliale qui conduit à la formation de la cicatrice gliale, ou encore l'inflammation dont les cellules microgliales et les mastocytes sont les effecteurs les plus précoces. Cette inflammation est connue pour exacerber les dommages tissulaires et restreindre les possibilités de récupération. Cependant, des études récentes chez l'animal et chez l'Homme montrent que l'inflammation pourrait également avoir des effets favorisant les processus de récupération. Le but de cette thèse était de mieux comprendre les liens qui existent entre neuroinflammation, neuroplasticité et récupérations fonctionnelles après lésion spinale. L’objectif expérimental visait à examiner les réactivités microgliales, mastocytaires et astrocytaires post-lésionnelles, en parallèle avec des restaurations fonctionnelles. Dans ce contexte nous nous sommes plus particulièrement intéressés à l'influence d'une cytokine pro-inflammatoire, le Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) sur ces processus inflammatoires et la plasticité fonctionnelle après une hémisection C4-C5 chez le rat adulte. L’ensemble de nos travaux suggère que le GM-CSF pourrait agir par l’intermédiaire de plusieurs événements cellulaires et moléculaires, en favorisant des phénomènes de plasticité adaptatifs et la récupération partielle de fonctions altérées. / Spinal cord injuries are mostly of traumatic origin and result in major sensorimotor deficits. Postlesion functional recovery is limited, especially because of the reduced capacity of repairing damaged tissues. Moreover, this recovery depends specifically on several cellular processes such as astroglial activation conducting to glial scar formation, or inflammation for which microglial and mast cells are the earliest effectors. This inflammation is known to exacerbate tissue damages and restrain the capacity to recover. However, recent studies in animals and humans show that inflammation may also have beneficial aeffects on recovery processes. The studies conducted during my doctoral research were intended to better understand the links between neuroinflammation, neuroplasticity and functional recovery following spinal cord injury. We aimed at examining microglial, mast cells and astroglial reactivities after the injury, in relation with functional recovery of somatosensory and motor functions. In this context, we were particularly interested in the influence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) on inflammatory and plasticity mechanisms after a C4-C5 hemisection in the adult rat. Our doctoral research suggests that GM-CSF could act through several cellular and molecular events promoting adaptive plasticity phenomena underlying partial recovery of impaired functions.

A lesão medular traumática é uma patologia incapacitante, ainda sem tratamento eficaz. As terapias celulares representam uma nova estratégia para o tratamento destas lesões. As células-tronco adultas são fontes potenciais para o transplante celular com o objetivo de minimizar a lesão e promover a recuperação de tecidos lesados, como a medula espinhal. O objetivo desta tese foi avaliar a eficácia do transplante de células-tronco adultas na recuperação funcional e regeneração da lesão medular traumática em modelo experimental de lesão medular contusa em ratas fêmeas Wistar. Os principais objetivos foram: a) comparar os efeitos do transplante da fração mononuclear de sangue de cordão umbilical humano e de células-tronco mesenquimais dos vasos da parede do cordão umbilical humano; b) determinar a janela terapêutica deste tipo de intervenção, comparando os implantes de células- tronco realizados 1 hora, 24 horas e 9 dias após a lesão; c) demonstrar a possível diferenciação das células-tronco implantadas, bem como sua integração no tecido lesado. Os resultados obtidos demonstraram que o transplante de células foi mais eficaz para a recuperação funcional da lesão medular em ratas Wistar quando realizado pela via de administração local 1h após a lesão, quando comparado com a administração na cisterna magna e a aplicação 9 dias a lesão. O tratamento com a fração de células mononucleares ou com as células-tronco mesenquimais do sangue do cordão umbilical 24h após a lesão, não apresentou resultado funcional significativo.Observou-se a neuroproteção do tecido medular quando foi realizado o transplante de células-tronco mesenquimais 1h após a lesão medular. As células humanas transplantadas migraram e sobreviveram no local da lesão quando administradas na cisterna magna ou quando administradas diretamente no local da lesão, porém não se diferenciaram em células gliais ou neurônios. Concluímos que o transplante de células-tronco adultas promoveu a recuperação funcional após a lesão medular contusa, principalmente quando realizado 1h após a lesão diretamente no local da lesão. Apesar das células transplantadas sobreviverem na área da lesão, não foi evidenciada diferenciação celular. / Spinal cord injury is a debilitating disease and yet no effective treatment is available. In this framework cell therapy represents a new strategy to treat this condition. Adult stem cells are potential sources for cell transplantation in order to minimize injury and promote the recovery of damaged tissues, such as the spinal cord. The purpose of this Thesis was to evaluate the action of adult stem cells in the regeneration and functional recovery of spinal cord injury in experimental contusion spinal cord injury in female Wistar rats. Main goals were: a) to compare the effects of transplantation of the mononuclear cells of human umbilical cord blood and mesenchymal stem cells of the vessel wall of human umbilical cord; b) to determine the therapeutic window of this type of intervention, comparing the stem cell implants performed 1 hour, 24 hours and 9 days after injury; c) to demonstrate the possible differentiation of cells implanted, as well as their integration into the damaged tissue. Results reported demonstrate that the transplantation of stem cells was more effective for functional recovery of spinal cord injury when performed into the site of the lesion 1 h after injury, as compared with administration in the cisterna magna 9 days after injury. Treatment with mononuclear cells and mesenchymal cells from umbilical cord blood 24 hours after injury, not showed functional outcome. Neuroprotection was observed when mesenchymal stem cells were transplanted 1 hour after spinal cord injury. The transplanted human cells survived and migrated to the site of injury either when administered in the cisterna magna or directly onto the injury site, but did not differentiated into glial cells or neurons. It is suggested that the transplantation of adult stem cells promotes functional recovery after spinal cord injury when performed 1 hour after injury directly at the injury site, however differentiation of transplanted cells was not detected.

No description available.

The capacity of the olfactory neuraxis to undergo neuronal replacement and axon targeting following injury, has led to scrutiny concerning the molecular and physical determinants of this growth capacity. This is because injury to the central nervous system, in contrast, leads to permanent disconnection of neurons with targets. Olfactory ensheathing cells (OECs), a specialized glial cell, may contribute to olfactory repair, and have been used to promote recovery from spinal cord injury. However, there mechanisms underlying OEC-induced regeneration are poorly appreciated. To understand these mechanisms, OECs from the lamina propria (LP OECs) or olfactory bulb (OB OECs) were transplanted into a lesion of the dorsolateral funiculus. While both cells demonstrated reparative capacities, LP and OB OECs differentially promoted spinal fibre growth; large-diameter neurofilament-positive, CGRP-positive, and serotonergic fibres sprouted in response to both LP and OB OEC transplantation, whereas substance-P and tyrosine hydroxylase-positive neurons grew more extensively following OB or LP OEC transplantation, respectively. To further understand the growth of spinal cord neurons in response to OECs, a proteomic analysis of OEC secreted factors was performed, identifying secreted protein acidic and rich in cysteines (SPARC) as a mediator of OEC-induced outgrowth in vitro. To test the contributions of SPARC to spinal cord repair after OEC transplantation, cultures of LP OECs from SPARC null and wildtype (WT) mice were transplanted into a crush of the dorsolateral funiculus. Substance P and tyrosine hydroxylase positive axon sprouting was significantly reduced in SPARC null OEC-treated animals, suggesting that individual factors may contribute to OEC-promoted regeneration. To investigate the effect of OECs on corticospinal (CST) neurons, an in vitro assay was developed using postnatal day 8 CST neurons. Coculture of CST neurons with OB OECs produced extensive axon elongation. Application of OB OEC secreted factors increased CST neurite branching, but did not increase axon elongation. In contrast, plating of CST neurons on OB OEC plasma membrane resulted in extensive axon elongation. Furthermore, the OB OEC plasma membrane could overcome CST neurite outgrowth inhibition induced by an outgrowth inhibitor. Together these findings provide insight into OEC mechanisms of neurite outgrowth and axon regeneration.

La récupération optimale des amplitudes articulaires (AAs) et de la force musculaire est un objectif crucial de la réadaptation fonctionnelle intensive (RFI) à la suite d’une lésion médullaire (LM). Le but de la présente étude était de documenter les changements d’AAs des membres supérieurs durant la RFI chez des individus (n = 197) ayant subi une LM et d’établir le lien avec l’autonomie fonctionnelle. Les données (AA, force musculaire, spasticité, déficiences secondaires, autonomie fonctionnelle) ont été collectées à l’admission et au congé de la RFI. Des analyses descriptives, des tests d’association entre les changements d’AAs et des variables indépendantes (douleur, spasticité, déficiences secondaires, force) et des analyses multivariées ont été utilisées. Les individus ayant une paraplégie présentent peu de déficit d’AAs à l’épaule comparés à ceux ayant une tétraplégie. Parmi ces derniers, une majorité présente des AAs sous les valeurs de normalité en fin de RFI. Le groupe D, établi selon l’évaluation de l’American Spinal Injury Association (ASIA D) présente des pertes d’AAs plus importante qu’attendue. La douleur au niveau articulaire est un facteur influençant les changements d’AAs, particulièrement dans ce groupe. La force musculaire chez les personnes ayant une tétraplégie sévère (ASIA ABC) est plus faible que celle du groupe ayant une lésion moins sévère (ASIA D). Généralement, le gain de force corrèle avec le gain d’AA. La force musculaire, les AAs et le nombre de déficiences secondaires sont les principaux éléments influençant l’autonomie fonctionnelle. En conclusion, la perte d’AA est plus importante à l’articulation de l’épaule et, pour plusieurs individus, malgré un gain significatif, les AAs n’atteignent pas les valeurs de référence au congé de la RFI. La force musculaire et certaines déficiences secondaires sont des éléments à considérer pour expliquer les pertes d’AAs et d’autonomie fonctionnelle. Les études futures devront clarifier certains aspects dont l’atteinte de la rotation médiale qui semble montrer un patron différent de récupération en comparaison des autres mouvements de l’épaule. De plus, les études devront montrer si ces changements et résultats sont maintenus après le congé de la RFI. / Optimal recovery of range of motion (ROM) and strength are critical objectives of intensive rehabilitation following spinal cord injury (SCI). The aim of this study was to characterize the evolution of ROM and strength at the upper limb and analyze their relationship with functional independence during intensive rehabilitation. Data ROM, strength, spasticity, secondary impairments, functional independence) from 197 participants with SCI were collected at admission and discharge from intensive rehabilitation and were analyzed with descriptive statistics and multivariate analyses (regressions, ANOVA). Specific association analyses were used to determine the level of association between ROM, strength and independent variables such as pain, spasticity and secondary impairments. Lesser deficit in ROM was observed in participants with paraplegia compared to those with tetraplegia. The deficit in individuals with tetraplegia was larger to an extent that most of them did not reach normality in ROM at shoulder joint. Surprisingly, individuals with less severe injury according to the American Spinal Injury Association classification (ASIA D) showed larger deficit of ROM than expected. Joint pain was related to reduce ROM, particularly in participants with ASIA D lesion. Values of muscle strength in individuals with more severe tetraplegia (ASIA ABC) are lower than the ones observed in individuals with less severe injury (ASIA D). Overall, strength and ROM were correlated, except for medial rotation movement. ROM, strength, and secondary impairments are the major determinants of functional independence. In conclusion, shoulder joint was the most affected joint of the upper limb, and, despite of significant gains of ROM, abnormalities were greater than expected. Strength and some secondary impairment were related in loss of ROM and functional independence throughout rehabilitation. More study will be needed to understand the medial rotation movement at the shoulder that seems to evolve differently from other movements, and to determine whether or not changes observed during rehabilitation are maintained over time.

L'évolution des soins médicaux auprès de la population ayant une lésion médullaire (LM) s'est traduite par une amélioration du profil fonctionnel des personnes atteintes. Ainsi une proportion importante retrouve une capacité à se tenir debout et à marcher qu'il convient d'évaluer adéquatement. Si quelques outils spécifiques à la population lésée médullaire existent pour évaluer leur ambulation, aucune évaluation de l'équilibre debout n'a été validée auprès de cette clientèle. L'échelle de Berg est un outil recommandé auprès de diverses populations, entre autres celles possédant des pathologies d'origine neurologique; et le score obtenu semble lié au niveau d'autonomie à la marche ainsi qu'aux aides techniques utilisées. L'objectif de ce projet de recherche était donc d'établir la validité concomitante de l'échelle de Berg auprès de la population LM et d'explorer les liens entre le score Berg et l'aide technique utilisée. Pour ce faire, trente-deux sujets BM ASIA D ont été recrutés parmi la clientèle hospitalisée de l'Institut de réadaptation Gingras-Lindsay de Montréal. L'évaluation de l'équilibre debout a été réalisée à l'aide de l'échelle de Berg ainsi que des tests statiques, dynamiques et des limites de stabilité du Balance Master. Le Walking Index for Spinal Cord Injury (WISCI), le Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), la vitesse de marche sur 10m et le Timed up and go ont été utilisés pour évaluer l'ambulation. Des analyses descriptives et corrélatives ont été effectuées sur les données obtenues. Une corrélation forte (0.714<Rs<0.816; p<0.01) a été observée entre l'échelle de Berg et les diverses évaluations de la marche. Des associations adéquates ont également été obtenues entre l'échelle de Berg et le test des limites de stabilité du Balance Master (-0.752<Rs<-0.463; p<0.01). Les épreuves statiques du Balance Master ont révélé de plus faibles corrélations avec les diverses mesures cliniques (-0.444<Rs<-0.414; p<0.01). Finalement, les épreuves dynamiques antéropostérieures et médiolatérales du Balance Master ont indiqué une relation équivoque avec l'échelle de Berg, n'étant reliées significativement qu'avec certaines épreuves en antéropostérieur (3 et 1s; -0.590<Rs<-0.524; p<0.01). Un effet plafond significatif est visible sur l'échelle de Berg, le WISCI et le SCI-FAI limitant leur utilité pour les personnes ayant une récupération supérieure. Les résultats ont aussi montré un profil différent des personnes tétraplégiques quant à la réussite des différentes épreuves du Berg par comparaison aux sujets paraplégiques. Pour les résultats reliés aux aides techniques, l’analyse des données descriptives révèlent que le score Berg permet généralement de faire la distinction entre les personnes indépendantes d'aides techniques, les utilisateurs de marchettes de béquilles ou de cannes, et ce, particulièrement pour les personnes paraplégiques. Cette étude a permis de documenter la validité concomitante de l'échelle de Berg auprès des personnes LM ayant une lésion incomplète (ASIA D) étant donné les relations élevées démontrées entre les paramètres de la marche et les résultats à certains tests du Balance Master. En somme, la présente étude permet de recommander l'utilisation de l'échelle de Berg pour évaluer l'équilibre debout des personnes LM. / The evolution of medical practices for people with spinal cord injury (SCI) has changed their functional profile with the result that a significant proportion recovers their ability to stand and walk. Implementing a validated scale to evaluate these aspects is therefore crucial during rehabilitation. Various walking scales have been developed specific to the SCI population, such as the Walking Index for Spinal Cord Injury (WISCI) and the Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI). However, no known balance evaluation has been recommended for this population. The Berg Balance Scale has been developed and validated for various populations presenting neurological disorders. An association has been shown between the Berg score and the level of independence as well as the walking assistive devices used. The purpose of this project was therefore to validate the Berg Balance Scale for the SCI population and to explore the relationship between the Berg score and the walking assistive devices used. Thirty-two subjects were recruited from the SCI population of the Institut de réadaptation Gingras-Lindsay de Montréal. Walking evaluation was performed using the WISCI, the SCI-FAI, the walking speed on 10m and the Timed Up and Go. The balance evaluation was carried out using the Berg Balance Scale (BBS) as well as the static, dynamic and limits-of-stability tests of the Balance Master. Descriptive and correlational analyses were performed on the sample. The results showed a strong correlation between the BBS and all walking evaluations (0.714<Rs<0.816; p<0.01). The BBS was also strongly related to the limits-of-stability test (-0.752<Rs<-0.463; p<0.01). The static tests of the Balance Master were weakly correlated with the various clinical evaluations (-0.444<Rs<-0.414; p<0.01) while the dynamic tests resulted in equivocal associations with BBS, being better for the anteroposterior test (3 and 1s conditions; -0.590<Rs<-0.524; p<0.01). A significant ceiling effect was present ion the BBS, the WISCI and the SCI-FAI scales. The results also showed that paraplegic and tetraplegic subjects differ in their performance in the various items of the BBS. Descriptive analysis reveals that the BBS score can help to discriminate between walker, crutches and cane users and individuals walking independently, especially in the case of people with paraplegia. This study revealed that the BBS is a valid balance evaluation for people with incomplete (ASIA D) spinal cord injury. Its use for evaluating standing balance in the clinical and laboratory setting is therefore recommended.

One of the most devastating effects of tetraplegia is the inability to grasp and manipulate everyday objects necessary to living an independent life. Currently surgery is widely accepted as the solution to improve hand functionality. However, surgery becomes difficult when the user has paralysed wrists as is the case with C5 tetraplegia. The aim of this research was to develop a solution which provided controlled wrist flexion and extension which, when combined with surgery, achieves a 'key pinch' grip. This particular grip is critically important for people with C5 tetraplegia as it is used for countless grasping activities, necessary on a day-to-day basis. A systematic design process was used to evolve the solution to provide controlled wrist flexion and extension. Concept brainstorming identified four alternative solutions which were evaluated to find the preferred concept. The chosen solution was called the Self Powered Wrist Extension Orthosis, more commonly referred to as the 'orthosis'. This concept contained a shoulder harness which provided both energy and control to the wrist harness, which in turn changed the wrist position. The orthosis was developed with the use of a mathematical model which theoretically predicted the functional performance by comparing the required force needed to move the wrist harness to the achievable force supplied by the user's shoulders. Using these parameters, the orthosis was optimized using the matlab Nelder-Mead algorithm which adjusted the wrist harness geometries to maximize the functional performance. A prototype was constructed and tested with the help of two participants who when combined, achieved an average of 18.5° of wrist rotation. The theoretical model however predicted an average range of motion of 28.4°. The discrepancy found between the theoretical and experimental result can be contributed to incorrect assumptions in the theoretical model. This included unaccounted friction and inaccurate modeling of the orthosis dynamics. The feedback from potential users of the orthosis was enthusiastic and encouraging especially towards the simplicity, usability and practicality of the design.

The capacity of the olfactory neuraxis to undergo neuronal replacement and axon targeting following injury, has led to scrutiny concerning the molecular and physical determinants of this growth capacity. This is because injury to the central nervous system, in contrast, leads to permanent disconnection of neurons with targets. Olfactory ensheathing cells (OECs), a specialized glial cell, may contribute to olfactory repair, and have been used to promote recovery from spinal cord injury. However, there mechanisms underlying OEC-induced regeneration are poorly appreciated. To understand these mechanisms, OECs from the lamina propria (LP OECs) or olfactory bulb (OB OECs) were transplanted into a lesion of the dorsolateral funiculus. While both cells demonstrated reparative capacities, LP and OB OECs differentially promoted spinal fibre growth; large-diameter neurofilament-positive, CGRP-positive, and serotonergic fibres sprouted in response to both LP and OB OEC transplantation, whereas substance-P and tyrosine hydroxylase-positive neurons grew more extensively following OB or LP OEC transplantation, respectively. To further understand the growth of spinal cord neurons in response to OECs, a proteomic analysis of OEC secreted factors was performed, identifying secreted protein acidic and rich in cysteines (SPARC) as a mediator of OEC-induced outgrowth in vitro. To test the contributions of SPARC to spinal cord repair after OEC transplantation, cultures of LP OECs from SPARC null and wildtype (WT) mice were transplanted into a crush of the dorsolateral funiculus. Substance P and tyrosine hydroxylase positive axon sprouting was significantly reduced in SPARC null OEC-treated animals, suggesting that individual factors may contribute to OEC-promoted regeneration. To investigate the effect of OECs on corticospinal (CST) neurons, an in vitro assay was developed using postnatal day 8 CST neurons. Coculture of CST neurons with OB OECs produced extensive axon elongation. Application of OB OEC secreted factors increased CST neurite branching, but did not increase axon elongation. In contrast, plating of CST neurons on OB OEC plasma membrane resulted in extensive axon elongation. Furthermore, the OB OEC plasma membrane could overcome CST neurite outgrowth inhibition induced by an outgrowth inhibitor. Together these findings provide insight into OEC mechanisms of neurite outgrowth and axon regeneration.