Spinal cord injury (SCI) is an acquired physical disability through traumatic injuries such as car accidents and shooting incidents, and non-traumatic injury such as a tumour on the spinal cord, amongst others. Unlike other parts of the body, the spinal cord does not have the ability to repair itself if it is damaged. Consequently, a person who has acquired an SCI will have a physical disability and will be either a paraplegic – paralysis of the lower part of the body, including the legs, or a quadriplegic, which is paralysis of all four limbs. Acquiring a spinal cord injury (SCI) has devastating long-term negative outcomes for the injured person as well as his/her cohabiting partner on a physical, psychological, psychosocial and socio-economical level. Exposure to such prolonged adversity and resulting negative outcomes calls for resilience, namely the ability to positively adapt despite the adversity being exposed to. Not all individuals have the natural ability to “bounce back”, and consequently resilience promotion is imperative. In South Africa, the focus of service delivery in rehabilitation centres is mainly centred on the injured person and consequently the well-being of the spinal cord injured person’s partner (SCIPP) is neglected. Little information is available on resilience-promoting programmes for SCIPPs; thus the main aim of this study was to design and develop a group resilience-promoting programme (GRPP) for SCIPPs. The researcher mainly followed a qualitative research approach and included a small quantitative component. In the context of applied research, an intervention research model comprising six phases was employed. Phase 1, Problem analysis and project planning, was reported on in section A. Manuscript 1 reports on phase 2 (information gathering and synthesis), and consists of a qualitative research synthesis, and mainly aimed at organizing and synthesizing previous research on resilience-promoting processes in order to inform the design and development of a group resilience-promoting programme (GRPP) for SCIPPs. After a systematic review and quality appraisal a total of 74 papers were selected to be quality appraised after abstracts and titles were assessed for relevance. Twenty-one studies were included and synthesized where after an outline for the content of a GRPP for SCIPPs was formulated. Conclusions and recommendations highlight that the formulated GRPP for SCIPPs needs to be further developed into an intervention that could be implemented with SCIPPs. As such, the researcher therefore proceeded with the study (see manuscript 2), aiming in developing small-group programme content and activities (using knowledge gathered from pre-existing interventions; resilience literature; consultations with experts; people living with spinal cord injury (SCI) and personal experience) to promote resilience in SCIPPs. By means of purposive sampling six advisory panel members from a diverse background were interviewed before and after the pilot study with two SCIPPs and one observer to contribute towards the further development of the GRPP for SCIPPs. A six-session GRPP for SCIPPs was formulated, including the following: (1) Information on SCI and resilience; (2) Help SCIPPs understand that their reactions to/emotions regarding these huge changes are normal; (3) Caretaking and support; (4) My dual role; (5) Own caretaking by SCIPPs; and (6) Termination and way forward. The newly developed GRPP for SCIPPs however had to be formally evaluated. Recommendations were made by professionals in the field that the GRPP for SCIPPs should first be subjected to peer review prior to implementing it with the target population. Therefore in manuscript 3 (reporting on phase 5 – evaluation ) the evaluation purpose was to subject the GRPP for SCIPPs to peer review by means of an empirical study with professional role-players (social workers and psychologists) in the field of spinal cord injury, prior to exhibiting it to the target population. The six group sessions were presented to professional role-players (n=12) working within the field of SCI during two 2-day workshops, whereby they were requested to evaluate the content and procedural elements of the GRPP for SCIPPs mainly by means of qualitative research, with a small numerical (quantitative) component. Thematic content analysis and basic descriptive statistics were employed. Overall positive feedback regarding the newly developed intervention was received, with suggested adjustments that needed to be made to the GRPP for SCIPPs prior to formal evaluation with the target group. The GRPP for SCIPPs will further be subjected to expert review in other provinces in South Africa, as the current participants were all from Gauteng. Furthermore, postgraduate students will be recruited to test the programme with the target-population in South Africa for possible further improvement and suggestions, as well as possible expansion to adjust this intervention to meet the needs of male SCIPPs; SCIPs themselves; children of a parent/s living with SCI; and also for post-injury cohabiting relationships, as this intervention might be a starting point for above-mentioned research-opportunities.

Spinal cord injury (SCI) is an acquired physical disability through traumatic injuries such as car accidents and shooting incidents, and non-traumatic injury such as a tumour on the spinal cord, amongst others. Unlike other parts of the body, the spinal cord does not have the ability to repair itself if it is damaged. Consequently, a person who has acquired an SCI will have a physical disability and will be either a paraplegic – paralysis of the lower part of the body, including the legs, or a quadriplegic, which is paralysis of all four limbs. Acquiring a spinal cord injury (SCI) has devastating long-term negative outcomes for the injured person as well as his/her cohabiting partner on a physical, psychological, psychosocial and socio-economical level. Exposure to such prolonged adversity and resulting negative outcomes calls for resilience, namely the ability to positively adapt despite the adversity being exposed to. Not all individuals have the natural ability to “bounce back”, and consequently resilience promotion is imperative. In South Africa, the focus of service delivery in rehabilitation centres is mainly centred on the injured person and consequently the well-being of the spinal cord injured person’s partner (SCIPP) is neglected. Little information is available on resilience-promoting programmes for SCIPPs; thus the main aim of this study was to design and develop a group resilience-promoting programme (GRPP) for SCIPPs. The researcher mainly followed a qualitative research approach and included a small quantitative component. In the context of applied research, an intervention research model comprising six phases was employed. Phase 1, Problem analysis and project planning, was reported on in section A. Manuscript 1 reports on phase 2 (information gathering and synthesis), and consists of a qualitative research synthesis, and mainly aimed at organizing and synthesizing previous research on resilience-promoting processes in order to inform the design and development of a group resilience-promoting programme (GRPP) for SCIPPs. After a systematic review and quality appraisal a total of 74 papers were selected to be quality appraised after abstracts and titles were assessed for relevance. Twenty-one studies were included and synthesized where after an outline for the content of a GRPP for SCIPPs was formulated. Conclusions and recommendations highlight that the formulated GRPP for SCIPPs needs to be further developed into an intervention that could be implemented with SCIPPs. As such, the researcher therefore proceeded with the study (see manuscript 2), aiming in developing small-group programme content and activities (using knowledge gathered from pre-existing interventions; resilience literature; consultations with experts; people living with spinal cord injury (SCI) and personal experience) to promote resilience in SCIPPs. By means of purposive sampling six advisory panel members from a diverse background were interviewed before and after the pilot study with two SCIPPs and one observer to contribute towards the further development of the GRPP for SCIPPs. A six-session GRPP for SCIPPs was formulated, including the following: (1) Information on SCI and resilience; (2) Help SCIPPs understand that their reactions to/emotions regarding these huge changes are normal; (3) Caretaking and support; (4) My dual role; (5) Own caretaking by SCIPPs; and (6) Termination and way forward. The newly developed GRPP for SCIPPs however had to be formally evaluated. Recommendations were made by professionals in the field that the GRPP for SCIPPs should first be subjected to peer review prior to implementing it with the target population. Therefore in manuscript 3 (reporting on phase 5 – evaluation ) the evaluation purpose was to subject the GRPP for SCIPPs to peer review by means of an empirical study with professional role-players (social workers and psychologists) in the field of spinal cord injury, prior to exhibiting it to the target population. The six group sessions were presented to professional role-players (n=12) working within the field of SCI during two 2-day workshops, whereby they were requested to evaluate the content and procedural elements of the GRPP for SCIPPs mainly by means of qualitative research, with a small numerical (quantitative) component. Thematic content analysis and basic descriptive statistics were employed. Overall positive feedback regarding the newly developed intervention was received, with suggested adjustments that needed to be made to the GRPP for SCIPPs prior to formal evaluation with the target group. The GRPP for SCIPPs will further be subjected to expert review in other provinces in South Africa, as the current participants were all from Gauteng. Furthermore, postgraduate students will be recruited to test the programme with the target-population in South Africa for possible further improvement and suggestions, as well as possible expansion to adjust this intervention to meet the needs of male SCIPPs; SCIPs themselves; children of a parent/s living with SCI; and also for post-injury cohabiting relationships, as this intervention might be a starting point for above-mentioned research-opportunities.

A lesão medular (LM) é uma patologia incapacitante que resulta em déficits sensoriais e motores. No Brasil, a incidência anual é de 30 novos casos de lesão medular a cada 1 milhão de indivíduos e, infelizmente, a LM permanece sem um tratamento eficaz. Células-tronco derivadas do dente decíduo humano estão entre as potenciais fontes de células-tronco para transplante após a lesão medular, cujo objetivo é de promover a proteção ou a recuperação da lesão na medula espinal. Buscou-se nesta tese avaliar os efeitos do transplante, uma hora após a lesão, das células tronco de dente decíduo humano (SHED) no período agudo, subagudo e crônico sobre a neuroproteção, proteção tecidual e recuperação funcional em ratos Wistar submetidos à lesão medular por contusão. Os principais objetivos foram: a) investigar os efeitos do transplante das SHED sobre a recuperação funcional, volume da lesão e morte neuronal; b) verificar os efeitos do transplante sobre as células progenitoras, formação da cicatriz glial e modificações astrocitárias após o modelo de contusão medular Observou-se a melhora na recuperação funcional, redução do volume da lesão e morte neuronal na medula espinal dos animais que receberam o transplante de SHED após a lesão medular. As SHED aumentam o número de células precursoras na medula espinal, no período subagudo, reduzem a expressão da proteína fibrilar glial ácida (GFAP) e aumentam a expressão do canal retificador de influxo de potássio 4.1, ambas proteínas astrocitárias. Concluímos que o transplante de células-tronco derivadas do dente decíduo humano após a lesão medular promove a recuperação funcional a partir do efeito neuroprotetor iniciado na fase aguda, confirmado pelo maior número de neurônios motores presentes seis semanas após a contusão. As SHED são capazes de aumentar o número de células precursoras e de produzir modificações astrocitárias na medula espinal de ratos lesados na fase subaguda, reduzindo a formação da cicatriz glial. / Spinal cord injury (SCI) is a disabling condition that results in sensory and motor deficits. The estimated annual incidence in Brazil is of 30 new cases of spinal cord injury per 1 million of individuals; unfortunately SCI remains without an effective treatment. Stem cells from human exfoliated deciduous teeth (SHED) are one among potential sources of stem cells for transplantation after spinal cord injury in order to promote protection or tissue and functional recovery after spinal cord injury. The aim of this Thesis was to evaluate the effects of stem cells from human exfoliated deciduous teeth (SHED) transplantation, one hour after lesion, in the acute, subacute and chronic phases on neuroprotection, tissue protection and functional recovery in Wistar rats submitted to spinal cord injury by contusion The main goals were: a) to investigate the effects of SHED transplantation on functional recovery, lesion volume, and neuronal death; b) to verify the effects of the transplantation on the progenitor cells number, glial scar formation and astrocytic modifications after spinal cord contusion. Improvement of functional recovery, reduction of lesion volume and neuronal death were observed in the spinal cord of animals submitted to spinal cord injury and SHED transplantation. SHEDs increased the number of precursor cells in the spinal cord in the subacute period, reduced the expression of glial fibrillary acidic protein (GFAP) and increased the expression of the potassium influx rectifier channel 4.1, both astrocyte proteins. We conclude that transplantation of stem cells from human exfoliated deciduous teeth after spinal cord injury promotes functional recovery from the neuroprotection effect, which starts in the acute phase and is confirmed six weeks after the contusion with a higher number of motor neurons in the ventral horn of spinal cord. SHEDs are able to increase the number of precursor cells and produce astrocyte modifications in the spinal cord of injured rats in the subacute phase, reducing glial scar formation.

Σκοπός: Η προσέγγιση και η αντιμετώπιση των κακώσεων της Αυχενικής Μοίρας της Σπονδυλικής Στήλης (ΑΜΣΣ) εξακολουθεί και σήμερα να παρουσιάζει διαφορές μεταξύ των διαφόρων κέντρων. Κατά καιρούς μάλιστα έχουν προταθεί πλείστοι τρόποι αντιμετώπισης: από συντηρητική με κρανιακή έλξη μέχρι πολύ επιθετική χειρουργική αντιμετώπιση με συνδυασμένες πρόσθιες και οπίσθιες προσπελάσεις. Στόχος της διατριβής ήταν η παρουσίαση της χειρουργικής εμπειρίας της Ορθοπαιδικής Κλινικής του Πανεπιστημίου Πατρών στην αντιμετώπιση των ασθενών αυτών και η ανάλυση των επιπλοκών των διαφόρων μεθόδων σταθεροποίησης. Έγινε προσπάθεια να απαντηθούν τα ακόλουθα ερωτήματα: 1) Ποια πρέπει να είναι σήμερα η διαγνωστική προσέγγιση των ασθενών με κάκωση στην ΑΜΣΣ; 2) Ποιοι ασθενείς χρειάζονται σταθεροποίηση; 3) Τι είδους σταθεροποίηση και ποιες είναι οι επιπλοκές αυτής; Ακολούθως, ποιος πρέπει να είναι ο σύγχρονος αλγόριθμος προσέγγισης των ασθενών με κακώσεις στην ΑΜΣΣ; 4) Ποιες είναι οι μακροχρόνιες επιπτώσεις της σταθεροποίησης; Μεθοδολογία: Εκατόν-δώδεκα ασθενείς με ασταθείς κακώσεις στην ΑΜΣΣ υποβλήθηκαν στην Κλινική μας σε πρόσθια, οπίσθια σταθεροποίηση ή και στις δύο. Ένας ασθενής θεωρούνταν ότι είχε ασταθή κάκωση της ΑΜΣΣ εάν είχε 5 ή παραπάνω βαθμούς με βάση τα κριτήρια αστάθειας των White & Panjabi. Τουλάχιστον ένας χρόνος παρακολούθησης (follow-up) ήταν αναγκαίος για να ενταχθεί ένας ασθενής στη μελέτη, με αποτέλεσμα να επιλεγούν τελικά 97 ασθενείς. Εβδομηντατέσσερις ασθενείς υποβλήθηκαν σε αριστερή προσθιοπλάγια προσπέλαση [Ομάδα Α]. Σε 65 ασθενείς έγινε πρόσθια αποσυμπίεση και τοποθέτηση φλοιοσπογγώδους λαγονίου αυτομοσχεύματος και σταθεροποίηση με πλάκα και βίδες, είτε με πλάκα της AO/ASIF ή με πλάκα CSLP. Στους υπόλοιπους 9 ασθενείς, η αποκατάσταση της σπονδυλικής στήλης περιελάμβανε τη χρήση κλωβού πλέγματος τιτανίου στο οποίο τοποθετούνταν σπογγώδη αυτομοσχεύματα από την περιοχή της σωματεκτομής. Εικοσιτρείς ασθενείς υποβλήθηκαν σε οπίσθια σταθεροποίηση είτε με πλάκες πλαγίων ογκωμάτων (πλάκες Roy-Camille) (19 ασθενείς), ή με πολυαξονικές βίδες (4 ασθενείς) [Ομάδα Β]. Αποτελέσματα – Συμπεράσματα: 1) Εφόσον η κλινική εικόνα ενός ασθενούς με κάκωση στην ΑΜΣΣ επιβάλλει τη διενέργεια αξονικής τομογραφίας, η διερεύνηση μπορεί να γίνει με ασφάλεια με τη χρήση ενός σύγχρονου πολυτομικού αξονικού τομογράφου (MDCT) και μόνο, παραλείποντας τις απλές ακτινογραφίες. 2) Τα κριτήρια αστάθειας των White και Panjabi υπαγορεύουν μια ασταθή κάκωση στην ΑΜΣΣ, η οποία θα πρέπει να αντιμετωπίζεται κατά προτίμηση με χειρουργικό τρόπο. 3) Η στατιστική ανάλυση των αποτελεσμάτων δεν ανέδειξε στατιστικά σημαντικές διαφορές μεταξύ των 2 ομάδων σταθεροποίησης όσον αφορά τις κλινικά σημαντικές επιπλοκές (p=0.26). Ομοίως, οι κλινικά μη σημαντικές επιπλοκές, καθώς και το ποσοστό επανεγχειρήσεων δε διέφεραν στατιστικά μεταξύ των δύο ομάδων (p=0.245 και p=0.475 αντίστοιχα). Ωστόσο, η πρόσθια σταθεροποίηση παρουσιάζει σημαντικά πλεονεκτήματα, μπορεί να αντιμετωπίσει το σύνολο σχεδόν των κακώσεων της ΑΜΣΣ συμπεριλαμβανομένου των εξαρθρημάτων, και μόνο κατ’ εξαίρεση απαιτείται συμπληρωματική σταθεροποίηση. Επιπλέον, η εξέλιξη της μεθόδου βοήθησε στην εξάλειψη επιπλοκών που παρατηρούνταν με τα παλαιότερης τεχνολογίας υλικά. Ως εκ τούτου, οι τρέχουσες ενδείξεις για οπίσθια σταθεροποίηση είναι τα μη ανατασσόμενα εξαρθρήματα, οι κακώσεις πολλαπλών επιπέδων και οι ασθενείς με τραχειοστομία. 4) Η οστεοποίηση των παρακειμένων διαστημάτων στις κακώσεις της ΑΜΣΣ φαίνεται ότι έχει διαφορετική αιτιολογία από αυτή της αυχενικής σπονδύλωσης, μπορεί να εμφανιστεί πολύ πρώιμα στην μετεγχειρητική περίοδο και, ακόμα και όταν είναι εμφανής ακτινολογικά, σπανίως προκαλεί συμπτώματα. / Aim: The diagnostic approach and management of patients with cervical spine injuries differs among various centers. Conservative management with skeletal traction to aggressive surgical treatment with combined anterior and prosterior stabilization are within the possible alternatives. We aimed at presenting the experience from the surgical treatment of these patients gathered in the Department of Orthopaedic Surgery in the University Hospital of Patras. We further analyzed the complications associated with each approach and we tried to answer the following questions: 1) Which is the current diagnostic approach of patients with cervical spine injuries? 2) Which patients should be stabilized? 3) What type the stabilization should be and which are its complications? Moreover, which is the appropriate algorithm in the treatment of these patients? 4) Which are the long-term consequences of the stabilization? Materials & Methods: One hundred and twelve patients with unstable cervical spine injuries underwent anterior, posterior stabilization or both. A patient was considered to have an unstable injury if he had ≥ 5 points in the White and Panjabi checklist. At least one year of follow-up was necessary for a patient to be included in the study, which yielded a total of 97 patients. Seventy-four patients underwent a left-sided anterolateral approach [Group A]. Sixty-five of them had anterior decompression and iliac bone grafting. The remaining 9 patients underwent corpectomy and cervical spine reconstruction with titanium mesh cage, filled with morselized autograft from the corpectomy site. All these patients were instrumented using an anterior cervical plate. Twenty-three patients underwent posterior stabilization, either with lateral mass plates of Roy-Camille (19 patients), or polyaxial screws and rods (4 patients) [Group B], along with concomitant iliac bone autografting. Results – Conclusions: 1) If there is a need for computed tomography (CT) in a patient with cervical spine injury, the diagnostic work-up can be done with safety using only a modern multi-detector CT, obviating the need for plain radiographs. 2) The White and Panjabi criteria imply an unstable injury which should be preferentially stabilized by surgical means. 3) Statistical analysis of the clinically significant complications did not reveal significant difference between the posterior procedures and the anterior ones (p=0.26). Likewise, insignificant complications, as well as reoperation rates did not differ significantly among the two groups (p=0.245 and p=0.475 respectively). However, anterior stabilization for cervical spine injuries presents several advantages, can deal with almost all types of injuries and it only exceptionally requires supplemental stabilization. It should be also stressed that the advances in technology and metallurgy have eliminated the complications observed with older implants. Current indications for posterior stabilization are the irreducible dislocations, multilevel injuries and patients with tracheostomy. 4) Adjacent-level ossification in cervical spine injuries appears to be of different etiology than in cervical spondylosis, it may appear very early in the postoperative period and, even when it is evident radiographically, it very rarely (if ever) produces any symptoms.

A lesão medular (LM) é uma patologia incapacitante que resulta em déficits sensoriais e motores. No Brasil, a incidência anual é de 30 novos casos de lesão medular a cada 1 milhão de indivíduos e, infelizmente, a LM permanece sem um tratamento eficaz. Células-tronco derivadas do dente decíduo humano estão entre as potenciais fontes de células-tronco para transplante após a lesão medular, cujo objetivo é de promover a proteção ou a recuperação da lesão na medula espinal. Buscou-se nesta tese avaliar os efeitos do transplante, uma hora após a lesão, das células tronco de dente decíduo humano (SHED) no período agudo, subagudo e crônico sobre a neuroproteção, proteção tecidual e recuperação funcional em ratos Wistar submetidos à lesão medular por contusão. Os principais objetivos foram: a) investigar os efeitos do transplante das SHED sobre a recuperação funcional, volume da lesão e morte neuronal; b) verificar os efeitos do transplante sobre as células progenitoras, formação da cicatriz glial e modificações astrocitárias após o modelo de contusão medular Observou-se a melhora na recuperação funcional, redução do volume da lesão e morte neuronal na medula espinal dos animais que receberam o transplante de SHED após a lesão medular. As SHED aumentam o número de células precursoras na medula espinal, no período subagudo, reduzem a expressão da proteína fibrilar glial ácida (GFAP) e aumentam a expressão do canal retificador de influxo de potássio 4.1, ambas proteínas astrocitárias. Concluímos que o transplante de células-tronco derivadas do dente decíduo humano após a lesão medular promove a recuperação funcional a partir do efeito neuroprotetor iniciado na fase aguda, confirmado pelo maior número de neurônios motores presentes seis semanas após a contusão. As SHED são capazes de aumentar o número de células precursoras e de produzir modificações astrocitárias na medula espinal de ratos lesados na fase subaguda, reduzindo a formação da cicatriz glial. / Spinal cord injury (SCI) is a disabling condition that results in sensory and motor deficits. The estimated annual incidence in Brazil is of 30 new cases of spinal cord injury per 1 million of individuals; unfortunately SCI remains without an effective treatment. Stem cells from human exfoliated deciduous teeth (SHED) are one among potential sources of stem cells for transplantation after spinal cord injury in order to promote protection or tissue and functional recovery after spinal cord injury. The aim of this Thesis was to evaluate the effects of stem cells from human exfoliated deciduous teeth (SHED) transplantation, one hour after lesion, in the acute, subacute and chronic phases on neuroprotection, tissue protection and functional recovery in Wistar rats submitted to spinal cord injury by contusion The main goals were: a) to investigate the effects of SHED transplantation on functional recovery, lesion volume, and neuronal death; b) to verify the effects of the transplantation on the progenitor cells number, glial scar formation and astrocytic modifications after spinal cord contusion. Improvement of functional recovery, reduction of lesion volume and neuronal death were observed in the spinal cord of animals submitted to spinal cord injury and SHED transplantation. SHEDs increased the number of precursor cells in the spinal cord in the subacute period, reduced the expression of glial fibrillary acidic protein (GFAP) and increased the expression of the potassium influx rectifier channel 4.1, both astrocyte proteins. We conclude that transplantation of stem cells from human exfoliated deciduous teeth after spinal cord injury promotes functional recovery from the neuroprotection effect, which starts in the acute phase and is confirmed six weeks after the contusion with a higher number of motor neurons in the ventral horn of spinal cord. SHEDs are able to increase the number of precursor cells and produce astrocyte modifications in the spinal cord of injured rats in the subacute phase, reducing glial scar formation.

A lesão medular (LM) é uma patologia incapacitante que resulta em déficits sensoriais e motores. No Brasil, a incidência anual é de 30 novos casos de lesão medular a cada 1 milhão de indivíduos e, infelizmente, a LM permanece sem um tratamento eficaz. Células-tronco derivadas do dente decíduo humano estão entre as potenciais fontes de células-tronco para transplante após a lesão medular, cujo objetivo é de promover a proteção ou a recuperação da lesão na medula espinal. Buscou-se nesta tese avaliar os efeitos do transplante, uma hora após a lesão, das células tronco de dente decíduo humano (SHED) no período agudo, subagudo e crônico sobre a neuroproteção, proteção tecidual e recuperação funcional em ratos Wistar submetidos à lesão medular por contusão. Os principais objetivos foram: a) investigar os efeitos do transplante das SHED sobre a recuperação funcional, volume da lesão e morte neuronal; b) verificar os efeitos do transplante sobre as células progenitoras, formação da cicatriz glial e modificações astrocitárias após o modelo de contusão medular Observou-se a melhora na recuperação funcional, redução do volume da lesão e morte neuronal na medula espinal dos animais que receberam o transplante de SHED após a lesão medular. As SHED aumentam o número de células precursoras na medula espinal, no período subagudo, reduzem a expressão da proteína fibrilar glial ácida (GFAP) e aumentam a expressão do canal retificador de influxo de potássio 4.1, ambas proteínas astrocitárias. Concluímos que o transplante de células-tronco derivadas do dente decíduo humano após a lesão medular promove a recuperação funcional a partir do efeito neuroprotetor iniciado na fase aguda, confirmado pelo maior número de neurônios motores presentes seis semanas após a contusão. As SHED são capazes de aumentar o número de células precursoras e de produzir modificações astrocitárias na medula espinal de ratos lesados na fase subaguda, reduzindo a formação da cicatriz glial. / Spinal cord injury (SCI) is a disabling condition that results in sensory and motor deficits. The estimated annual incidence in Brazil is of 30 new cases of spinal cord injury per 1 million of individuals; unfortunately SCI remains without an effective treatment. Stem cells from human exfoliated deciduous teeth (SHED) are one among potential sources of stem cells for transplantation after spinal cord injury in order to promote protection or tissue and functional recovery after spinal cord injury. The aim of this Thesis was to evaluate the effects of stem cells from human exfoliated deciduous teeth (SHED) transplantation, one hour after lesion, in the acute, subacute and chronic phases on neuroprotection, tissue protection and functional recovery in Wistar rats submitted to spinal cord injury by contusion The main goals were: a) to investigate the effects of SHED transplantation on functional recovery, lesion volume, and neuronal death; b) to verify the effects of the transplantation on the progenitor cells number, glial scar formation and astrocytic modifications after spinal cord contusion. Improvement of functional recovery, reduction of lesion volume and neuronal death were observed in the spinal cord of animals submitted to spinal cord injury and SHED transplantation. SHEDs increased the number of precursor cells in the spinal cord in the subacute period, reduced the expression of glial fibrillary acidic protein (GFAP) and increased the expression of the potassium influx rectifier channel 4.1, both astrocyte proteins. We conclude that transplantation of stem cells from human exfoliated deciduous teeth after spinal cord injury promotes functional recovery from the neuroprotection effect, which starts in the acute phase and is confirmed six weeks after the contusion with a higher number of motor neurons in the ventral horn of spinal cord. SHEDs are able to increase the number of precursor cells and produce astrocyte modifications in the spinal cord of injured rats in the subacute phase, reducing glial scar formation.

Acute spinal cord injury is often caused by collisions with motor vehicles, falls or violence. This injury could potentially lead to paraplegia or tetraplegia, causing great economic and personal loss. The patophysiology is biphasic, with primary and secondary mechanisms. Regarding secondary spinal cord injury, glutamate and interleukin-1 beta (IL-1<img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Cbeta" data-classname="equation" data-title="" />) activates N-methyl-d-aspartate (NMDA)-receptors leading to prolonged excitotoxity, causing neuronal death and subsequently glial scarring. Cross-linked-hyaluronic acid gel and interleukin-1 receptor antagonist (IL-1RA) are believed to have a neuroprotective effect. The major aim of this study was to evaluate neuroprotection in the central neural system. Briefly, spinal cord slice cultures from mice (p9-12) were chemically injured with NMDA and treated with two hyaluronic acid-based gels with integrated, or added, IL1RA. RNA was extracted and transcripted to cDNA. The gene expression of Neuronal nuclear protein, <img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Cbeta" data-classname="equation" data-title="" />-aktin and IL-1<img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?%5Cbeta" data-classname="equation" data-title="" /> were studies with RT-qPCR. Results showed that gel integrated with IL1RA had significant therapeutic effect, resembling undamaged cultures. Furthermore, axonal outgrowth was investigated in dorsal root ganglion (DRG) in which two preparations of the method were evaluated. Results demonstrated that changing medium every other day was more preferred, compared to adding 20 µl medium every day.  In conclusion, gels integrated with IL1RA have neuroprotective properties and in DRG preparations, medium should be changed every other day for optimal results.

Indiana University-Purdue University Indianapolis (IUPUI) / Human traumatic spinal cord injuries (SCI) are primarily incomplete contusion or compression injuries at the cervical spinal level, causing immediate local tissue damage and a range of potential functional deficits. Secondary damage exacerbates initial mechanical trauma and contributes to function loss through delayed cell death mechanisms such as apoptosis and autophagy. As such, understanding the dynamics of cervical SCI and related intracellular signaling and death mechanisms is essential. Through behavior, Western blot, and histological analyses, alterations in phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K) signaling and the neuroprotective, functional, and mechanistic effects of administering the protein tyrosine phosphatase (PTP) inhibitor, potassium bisperoxo (picolinato) vanadium ([bpV[pic]) were analyzed following cervical spinal cord injury in rats. Furthermore, these studies investigated the combination of subacute Schwann cell transplantation with acute bpV(pic) treatment to identify any potential additive or synergistic benefits. Although spinal SC transplantation is well-studied, its use in combination with other therapies is necessary to complement its known protective and growth promoting characteristics. v The results showed 400 μg/kg/day bpV(pic) promoted significant tissue sparing, lesion reduction, and recovery of forelimb function post-SCI. To further clarify the mechanism of action of bpV(pic) on spinal neurons, we treated injured spinal neurons in vitro with 100 nM bpV(pic) and confirmed its neurprotection and action through inhibition of PTEN and promotion of PI3K/Akt/mammalian target of rapamycin (mTOR) signaling. Following bpV(pic) treatment and green fluorescent protein (GFP)-SC transplantation, similar results in neuroprotective benefits were observed. GFP-SCs alone exhibited less robust effects in this regard, but promoted significant ingrowth of axons, as well as vasculature, over 10 weeks post-transplantation. All treatments showed similar effects in forelimb function recovery, although the bpV and combination treatments were the only to show statistical significance over non-treated injury. In the following chapters, the research presented contributes further understanding of cellular responses following cervical hemi-contusion SCI, and the beneficial effects of bpV(pic) and SC transplantation therapies alone and in combination. In conclusion, this work provides a thorough overview of pathology and cell- and signal-specific mechanisms of survival and repair in a clinically relevant rodent SCI model.

Les lésions traumatiques de la moelle épinière entraînent de graves conséquences d’un point de vue personnel, physique et social chez les individus qui en sont victimes. La prise en charge médicale et chirurgicale de ces patients évolue au fil de l’amélioration des connaissances sur ce qui favorise la récupération neurologique et la qualité de vie à long terme. Pour le chirurgien du rachis, les facteurs modifiables qui influencent de façon significative l’issue neurologique à long terme chez les blessés médullaires thoraco-lombaires sont peu explorés dans la littérature. Le délai entre le trauma et l’exécution du geste chirurgical est un de ces facteurs, mais la définition de chirurgie précoce chez cette population spécifique demeure à être objectivée. De plus, il n’y a pas de paramètres sur le scan préopératoire ayant été décrit pour aider la prise en charge en fonction de l’issue neurologique à long-terme. L’objectif général de ces travaux est de préciser ce qui influence la récupération neurologique chez les patients paraplégiques ayant subi une fracture dans la région thoraco-lombaire et évaluer l’impact de la morphologie de la fracture sur l’effet du délai entre le traumatisme et la chirurgie de décompression et de stabilisation de la colonne vertébrale. Le premier volet de ce mémoire concerne l’étude du seuil de délai chirurgical associé à une récupération neurologique optimale. Pour ce faire, une étude clinique rétrospective a été menée en évaluant plusieurs issues neurologiques à long terme chez une cohorte prospective de 35 patients blessés médullaires secondairement à un traumatisme vertébral de la région thoraco-lombaire. Déterminer de façon objective le seuil de délai optimal pour la récupération neurologique a été possible en utilisant une méthode statistique faisant intervenir des modèles de prédiction sous la forme d’arbres décisionnels élaborés par partition objective récursive. Cette méthode a démontré que la chirurgie de décompression et de stabilisation entreprise dans les 21 heures suivant le moment du traumatisme augmente la probabilité d’améliorer l’état neurologique 12 mois après le traumatisme, en termes de sévérité (grade) de la lésion et du niveau neurologique. Le deuxième volet du mémoire concerne l’étude de la morphologie de la fracture la plus commune de la région thoraco-lombaire, la fracture de type « burst ». De nombreux paramètres radiologiques sont connus et définissent ce type de fracture mais aucun n’a été bien évalué en fonction de la récupération neurologique à long terme. Une deuxième étude clinique rétrospective implique l’étude du scan préopératoire à la recherche de paramètres reliés à l’issue neurologique chez les blessés médullaires avec atteinte motrice sévère. Trois caractéristiques morphologiques fortement associées à la récupération ont été identifiées : la présence d’une fracture complète de la lame, le recul de plus de 4 mm de la portion inférieure du mur postérieur du corps vertébral et la présence de comminution du fragment de corps vertébral rétropulsé dans le canal spinal. Ces paramètres sont des facteurs de pronostic défavorable de récupération neurologique plus importants que l’atteinte neurologique initiale ou l’estimation du degré d’énergie impliquée durant le traumatisme. Puisque ces paramètres décrivent la géométrie du canal spinal endommagé lors d’une fracture de type « burst », ils offrent un reflet de l’énergie locale dissipée dans le canal spinal et transmise aux éléments neuraux. Le troisième volet du mémoire implique l’intégration des nouvelles connaissances issues des deux articles présentés, à la recherche de l’influence de certains paramètres morphologiques sur l’effet de la chirurgie précoce sur la récupération neurologique. Les analyses complémentaires effectuées sur la cohorte de patients atteints de fracture de type « burst » n’ont pas démontré que l’avantage procuré par une chirurgie de décompression et stabilisation précoce était modifié ou altéré par la présence d’un des paramètres démontrés comme importants d’un point de vue neurologique. Ces travaux permettent de mieux guider le chirurgien du rachis dans la planification du geste chirurgical de par une meilleure compréhension des facteurs prédictifs de l’issue neurologique à long terme. En déterminant un seuil de délai objectif optimal de 21 heures, ils permettent d’établir une recommandation pour la définition même de la chirurgie précoce chez le blessé médullaire thoraco-lombaire. Ils proposent également une base pour l’étude subséquente de nouveaux paramètres clés quantifiables sur le scan préopératoire, un examen essentiel et disponible chez tous les patients, et de leur relation potentielle avec le choix de l’approche chirurgicale idéale ainsi qu’avec de multiples issues neurologiques et non-neurologiques. / Traumatic spinal cord injury (TSCI) is a debilitating condition that leads to many adverse consequences on a personal, physical and social standpoint for the injured victim. Medical and surgical care evolved along with the progression of understanding regarding what factors lead to better neurological recovery and overall quality of life in paralyzed patients. With respect to surgical care, modifiable factors significantly related to neurological recovery in thoracolumbar TSCI are not well known. In this regard, the optimal timing threshold for surgical spinal decompression and stabilization has not been demonstrated objectively. Moreover, there are no radiological parameter on the pre-operative computed tomography scan (CT scan) that have been shown to predict long term neurological outcome. The main goal of the presented work is to provide precise identification of such factors, and therefore evaluate the impact of the spine fracture specific morphological features on the effect of early surgical care. The first part involves the assessment of the optimal surgical timing threshold for neurological recovery. A retrospective clinical study was conducted to evaluate several neurological outcome measures in a prospective cohort of 35 thoracolumbar TSCI patients. Thresholds were obtained from the elaboration of prediction models with the use of Classification And Regression Tree (CART) statistical analysis. The first article demonstrated that for optimal recovery of the neurological level of injury, a timing threshold of a maximum of 21 hours should ideally be respected between the traumatic event and the beginning of the surgical intervention. The second part encompasses the study of the morphology of the fractured vertebrae in thoracolumbar burst fractures. Many radiological descriptors are used to describe these severe spine compression injuries but few have been evaluated with regards to neurological recovery. A second retrospective clinical study was conducted and associated a thorough examination of the preoperative CT scan reconstructions to the assessment of long term neurological outcome. Three morphologic parameters were found to be linked to poor prognostic of neurological recovery: complete lamina fracture, comminution of the posteriorly retropulsed fragment and vertebral body postero-inferior corner translation of 4 mm or more. Such features, all three describing the disrupted anatomy of the spinal canal, could be potential indicators of the amount of energy locally dissipated to the neural elements. These parameters were found to be more important to predict neurological outcome than the initial neurologic examination and global trauma energy indicators. The third part integrates the notions derived from the two presented studies and aims to assess for the influence of the presence of specific fracture parameters on the effect of early surgery regarding neurological outcome. Additional analyses did not show that the advantage of early surgery, defined in the first article, was influenced by the presence of any of the relevant fracture features demonstrated in the second article. Therefore, this work emphasizes on the importance of early surgery for better neurological recovery and serves to guide the surgeon in planning the timing of the intervention. Defining the concept of early surgery is key in implementing future retrospective or prospective research protocols. It also highlights the importance of new morphological features of the most common type of thoracolumbar fracture. It sets standards for further research involving preoperative CT scan parameters and their potential relationship with surgical approach, neurological and non-neurological outcomes.

Lower-limb exoskeletons are an emerging technology to provide walking assistance to people who have a spinal cord injury (SCI). Until now, exoskeletons have primarily been used in a clinical setting for a range of applications in rehabilitation, and there is potential for exoskeletons to be used by people with SCI at home. Daily walking with an exoskeleton contributes significantly to physical and mental health of the user, but previous work has concluded that further development is required before exoskeletons are broadly adopted for this purpose. ABLE Human Motion is currently working to create a lightweight and intuitive exoskeleton for home use. To understand how this exoskeleton must be designed differently from clinical rehabilitation exoskeletons, it is necessary to understand the user requirements of the device in depth. This thesis explored: 1) what methodology is appropriate for evaluating home use exoskeletons, 2) what users want to use a personal exoskeleton for, and 3) what design changes distinguish an exoskeleton for home use instead of rehabilitation. This was done using a combination of literature review, hazard analysis, user observations (n=7), user interviews (n=7), and physiotherapist interviews (n=3) to derive a detailed set of user requirements and product specifications for a personal exoskeleton for home use. Interviews were conducted face-to-face and analyzed using thematic analysis. Results of the study show that users primarily want to use a personal exoskeleton for daily exercise and wellness activities, in outdoor environments, and around the theme of “like-everyone-else”. Therapists added an additional theme of user trust in the device. These insights have been translated into a set of prioritized user requirements and product specifications for a lower-limb exoskeleton for walking assistance after SCI, which can be used in the future design and development of such a device. Future work will be to develop testing setups to further explore the product specifications, and to conduct observation studies of the exoskeleton being used in a home-like environment. / Exoskelett för de nedre extremiteterna är en framväxande teknik för att ge gångassistans till personer som har en ryggmärgsskada. Hittills har exoskelett främst använts i en klinisk miljö för en rad tillämpningar inom rehabilitering, men det finns potential för exoskelett att användas av personer med ryggmärgsskada för personligt bruk i hemmet. För att förstå hur personliga exoskelett måste utformas annorlunda än kliniska exoskelett är det nödvändigt att på djupet förstå användarens krav på enheten. Detta projekt använde en kombination av litteraturgranskning, riskanalys, användarobservationer, användarintervjuer och fysioterapeutintervjuer för att härleda en detaljerad uppsättning användarkrav och produktspecifikationer för ett personligt exoskelett för hemmabruk. Intervjuer analyserades med hjälp av tematisk analys. Resultaten av studien visar att användarna i första hand vill använda ett personligt exoskelett för dagliga tränings- och hälsoaktiviteter, i utomhusmiljöer och på temat ”som alla andra”. Andra viktiga teman för framtida utveckling var kring användarnas förtroende för enheten och bibehållande av motivation för daglig träning. Dessa teman har översatts till en uppsättning prioriterade användarkrav och produktspecifikationer för ett nedre extremitetsskelett för gångassistans efter en ryggmärgsskada som kan användas i framtida design och utveckling av en sådan enhet.