Hereditary spastic paraplegia type 54 is a rare autosomal recessive neurological gait disorder characterized by paraplegia, muscle spasticity, and intellectual disability. This length-dependent distal axonopathy is caused by mutations in the DDHD2 gene, which encodes the intracellular phospholipase A1 DDHD2. Little is known about the molecular function of the DDHD2 protein, especially in the context of HSP54. Thus, there is a need to further investigate its molecular functions and investigate the impact of DDHD2 deficiency in disease-relevant cells. Here, lipidomic profiling of dermal fibroblasts derived from three unrelated patients has revealed 19 glycerophosphoethanolamine species at differential levels in patients relative to unaffected controls. However, patient cells appear to have an unaffected Golgi apparatus morphology and lipid droplet formation, despite DDHD2’s proposed roles in these processes. To study the gene function in neuronal cells, I transdifferentiated the fibroblasts into induced neuronal precursor cells and found all the patient cells arrested in the G0/G1 phase of upon conversion. Given that these cell lines are unsustainable, I generated a stable knockdown cell line in the highly proliferative HEK293A to study the molecular biology of DDHD2. The knockdown cells had a reduced growth, were delayed in the G2/M phase of the cell cycle, and became multinucleated. I then treated the cells with antineoplastic compounds paclitaxel and nocodazole and found more knockdown cells in G0/G1 than controls, suggesting the possible occurrence of mitotic slippage. Lastly, I report a novel subcellular localization for DDHD2 at the microtubule organization center.

Les mutations du gène des protéolipoprotéines, PLP1, codant des protéines structurales majeures de la myéline du système nerveux central : PLP et DM20, sont responsables d'un sous-groupe de leucodystrophies dysmyélinisantes liées à l'X. La forme la plus sévère, la maladie de Pelizaeus-Merzbacher (PMD), induite principalement par des duplications du gène conduit à une hypomyélinisation majeure ; tandis que la forme la plus modérée, la paraplégie spastique de type 2 (SPG2), induite par des mutations non-sens ou des délétions du gène conduit à une myéline mal compactée et une dégénérescence axonale tardive. Ce travail de thèse porte sur la caractérisation phénotypique de souris transgéniques mâles présentant une invalidation du gène Plp1 (souris Plp null), ainsi que des femelles hétérozygotes pour cette mutation et surexprimant le gène Plp1 (souris PLOA), modèles des mères transmettrices de ces maladies. Une étude longitudinale du comportement de ces souris a été réalisée et a permis de mettre en évidence chez les souris mâles Plp null l'apparition de troubles moteurs, sensitifs et cognitifs, qui ont pu ensuite être reliés à des anomalies d'expression (1) de marqueurs astrocytaires ou microgliaux et de neuropeptides impliqués dans la douleur au niveau de la moelle épinière, (2) de marqueurs ayant un rôle dans les processus cognitifs dans le cerveau et notamment dans certaines régions de l'hippocampe et (3) à des altérations des vitesses de conduction nerveuse. Chez les femelles mutées Plp1, les anomalies comportementales semblent liées au génotype, avec le développement de symptômes uniquement chez les mères porteuses de mutation modérée. Depuis quelques années, un ensemble de données évoquent un rôle de la substance blanche, et notamment la myéline, dans les fonctions comportementales et cognitives. Les résultats obtenus au cours de ce travail confirment l'intérêt des souris Plp null pour mieux comprendre ce rôle. De plus, les nombreuses similarités identifiées entre les modèles animaux et la pathologie humaine permettent d'envisager l'utilisation de ces modèles pour l'évaluation de nouvelles stratégies thérapeutiques. Nous avons ainsi évalué l'efficacité d'un neuroleptique atypique sur les troubles comportementaux des souris mâles Plp null. / Mutations of the proteolipoprotein gene, PLP1, coding the major structural proteins of the central nervous system, PLP and DM20, are responsible of some X-linked dysmyelinating leukodystrophies. The most severe form, the Pelizaeus-Merzbacher disease (PMD), due to gene duplications, causes a major hypomyelination ; while the moderate form, the spastic paraplegia type 2 (SPG2), due to non-sense mutations or gene deletions, leads leading to unpacked myelin and late axonal degeneration. This thesis work focuses on phenotypic characterization of transgenic male mice with Plp1 invalidation (Plp null mice), together with heterozygous females for this mutation and overexpressing Plp1 (PLOA mice), models of carrier mothers of these diseases. A longitudinal study on mice behavior was performed and allowed to highlight in Plp null male mice, the onset of motor, sensitive and cognitive defects, then linked to expression abnormalities of (1) astrocytic or microglial markers and neuropeptides involved in painful processes in spinal dorsal horn, (2) markers implied in cognitive processes in brain and especially some hippocampus regions, (3) alterations of nerve conduction velocities. In Plp1-mutated females, behavior abnormalities seem to be related to genotype, with development of symptoms only in females carrying moderate mutation. Since few years, data suggest a role of white matter, and particularly myelin, in cognitive and behavioral functions. Results of this study confirm the interest of Plp null mice to better understand this role. Further, similarities identied between animal models and human pathology, allow to consider these models to assess new therapeutic perspectives. We thus assessed the efficiency of a typical neuroleptic on Plp null mice behavioral alterations.

Title: The evaluation of functional sitting stability of paraplegics Objectives: The aim of this work is to evaluate the functional stability of paraplegics sitting through tests. Another objective is to determine what is the effect of fourteen days rehabilitation intervention on the sitting patients. Methods: Designed experiment was processed by the form of quantitative research. There were 10 pacients with spinal cord injuries, especially paraplegics included - 5 men and 5 women. The history was detected with the main emphasis on assessment ASIA score. Measurement of unsupported upright sitting was done thanks to the Plantograf V09. It records the current pressure distribution and movement of the center of pressure (COP). Functional T - shirt test was evaluated by using a stopwatch. Probands responded two questions about their current condition after rehabilitation after the output measuring. The therapist rating was included in the results. All data were further processed in Microsoft Office Excel 2007. Results: Measurements confirmed the reliability of both used tests. The t-shirt test can be used as an objective method of assessing functional stability of sitting. Test of unsupported upright sitting measured by Plantografu is also usable. It would be appropriate to set the measuring apparatus...

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Problématique. L'utilisation d'un chien d'assistance à la mobilité (CAM) représente une option novatrice pour préserver l’intégrité des membres supérieurs (MSs) chez les utilisateurs de fauteuil roulant manuel (FRM). Aucune étude biomécanique n’a quantifié les effets du CAM sur les efforts aux MSs lors de la montée d’un plan incliné. Objectif. Cette étude quasi-expérimentale vise à comparer les efforts aux MSs lors de la montée d’un plan incliné avec et sans l’assistance d’un CAM. Méthodologie. Dix participants avec une lésion de la moelle épinière (LME) qui utilisent un FRM et possèdent un CAM ont monté un plan incliné à trois reprises avec et sans l’assistance du CAM. Les forces appliquées sur les cerceaux, mesurées avec des roues instrumentées, et les mouvements du FRM et des MSs, enregistrés avec un système d'analyse du mouvement, ont permis de mesurer les efforts mécaniques aux MSs. Simultanément, l'activité électromyographique (EMG) des muscles grand pectoral, deltoïde antérieur, biceps et triceps a été enregistrée et normalisée avec sa valeur maximale pour mesurer les efforts musculaires aux MSs. Résultats. En général, le CAM réduit significativement les valeurs moyennes et maximales de la force totale appliquée aux cerceaux et de sa composante tangentielle, des moments nets de flexion, de rotation interne et d’adduction aux épaules et des taux d’utilisation musculaire du deltoïde antérieur, du biceps et du triceps. Conclusion. L’assistance d’un CAM réduit les efforts aux MSs lors de la montée d’un plan incliné chez les utilisateurs d’un FRM ayant une LME. / Problematic. The use of a mobility assistance dog (ADMob) represents an innovative option to preserve upper limb (U/Ls) integrity in manual wheelchair (MWC) user population. No biomechanical studies have quantified the effects of ADMob on U/Ls efforts when climbing an incline. Objective. This quasi-experimental study compares the U/Ls efforts when climbing an incline with and without the assistance of an ADMob for MWC traction. Methodology. Ten participants with spinal cord injury (SCI) using a MWC and owning an ADMob climbed an incline 3 times with and without the use of an ADMob. The forces applied to the handrims, captured with instrumented wheel and movements of the MWC and the U/Ls, recorded with a three-dimensional motion analysis system, were used to measure the U/Ls mechanical efforts. Simultaneously, the electromyographic (EMG) activity of the pectoralis major muscle, anterior deltoid, biceps and triceps were recorded during the tasks and normalized with its maximum value to measure the U/Ls muscular efforts. Results. Typically, ADMob significantly reduces the mean and peak values of the total force applied to the rings and the tangential component, the mean and peak values of flexion, internal rotation and adduction net joint moments at the shoulder and the mean and peak values of muscular utilization ratio of anterior deltoid, pectoralis major, biceps and triceps. Conclusion. The assistance of an ADMob for MWC traction when climbing an incline reduces the effort to U/Ls among MWC users with a SCI.

No description available.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Text in Afrikaans / Indigenous literature about the experience of a couple, where one of the spouses experiences a spinal cord injury, is scarce in the frame of social work. The experience of 5 couples (10 participants), after a spinal cord injury of one of the spouses was researched in this qualitative study. The aim of this research study is: • to reconnoiter participants’ experience of a spinal cord injury of a spouse, through semi-structured interviews with a purposeful chosen sample • to subject the research findings to a literature control • to make recommendations about how spouses can support each other, as well as how professional people can support client systems, where one of the spouses experience a spinal cord injury From the data it was determined that a spinal cord injury had significantly influenced the couples: - emotions - needs - perceptions (origination of experiences) Recommendations to couples as well as to professional people have been made. / Social Work / Thesis (M. Diac.)

Text in Afrikaans / Indigenous literature about the experience of a couple, where one of the spouses experiences a spinal cord injury, is scarce in the frame of social work. The experience of 5 couples (10 participants), after a spinal cord injury of one of the spouses was researched in this qualitative study. The aim of this research study is: • to reconnoiter participants’ experience of a spinal cord injury of a spouse, through semi-structured interviews with a purposeful chosen sample • to subject the research findings to a literature control • to make recommendations about how spouses can support each other, as well as how professional people can support client systems, where one of the spouses experience a spinal cord injury From the data it was determined that a spinal cord injury had significantly influenced the couples: - emotions - needs - perceptions (origination of experiences) Recommendations to couples as well as to professional people have been made. / Social Work / Thesis (M. Diac.)