O estudo foi realizado com pessoas do sexo masculino e que viveram a experiência de sofrer um trauma que acarretou a lesão da medula espinal. Teve como objetivos: - compreender os significados que a pessoa atribui a sua experiência de ser lesado medular; - compreender a maneira como a dimensão atribuída ao significado de ser lesado medular se manifesta nas ações da pessoa; - desenvolver um modelo teórico representativo da experiência da pessoa que sofreu uma lesão traumática na medula espinal. Utilizou-se como referencial teórico o Interacionismo Simbólico e como referencial metodológico, a Teoria Fundamentada nos Dados. A estratégia para a obtenção dos dados foi a entrevista. Dos resultados emergiram dois fenômenos - Sobrevivendo ao Acidente e Vivendo uma Nova Realidade. Destes, identificou-se a categoria central - Re dimensionando limitações e possibilidades. A compreensão da experiência da pessoa que adquire uma lesão da medula espinal possibilitou reconhecer como as vivências, que ocorrem após a constatação da deficiência física, são percebidas por esses indivíduos, e como redimensionam os significados que vão atribuindo às situações diferentes que passam a vivenciar. O modelo teórico mostra que a experiência de ter se tornado um paraplégico ou um tetraplégico, é permeada pela vivência de limitações, e dependências, sentimentos e reações que vão sendo dimensionados e redimensionados à medida que vai re elaborando significados e valores, e desenvolvendo ações que lhe apontam possibilidades, as quais toma posse mediante as escolhas que faz para dar continuidade ou sentido à vida preservada, porém modificada / A study conducted with adult males who had undergone the experience of suffering trauma causing spinal cord injury (SCI). The aim was to: - understand the meaning patients gave to their experience of being an SCI bearer; - understand how the dimensions attributed to being a SCI bearer manifested itself in the person\'s behavior; - develop a theoretical model representative of the experience of the person who suffered SCI. The study used as a theoretical reference Symbolic Interactionism and used the Grounded Theory methodology. Data was collected through interviews. Two phenomena emerged from the findings: \"Surviving the Accident\" and \"Living a New Reality\". Of these the central category was identified as Re defining limits and possibilities. Understanding of the experience of SCI bearers made it possible to recognize how the events that occurred after the diagnosis of the physical deficiency is perceived by the persons and how they redefine the meaning attributed to the different situations they came to experience after suffering the acquired physical deficiency. The theoretical model reveals that the experience of having become a paraplegic or tetraplegic involved a lot of coping with limitations and dependency, emotions and reactions that go on being defined and redefined as the individual restructured values and developed actions that led to possibilities of overcoming, which were adopted through the choices made, so as to give continuity of meaning to the life that remained, although in its modified state

A regeneração de danos às células nervosas do sistema nervoso central (SNC) é limitada devido aos fatores intrínsecos ao próprio nicho celular. A cicatriz glial, a liberação de inibidores de crescimento axonal, e a ação fagocítica dos astrócitos são fatores que limitam essa regeneração, coibindo os processos de reestruturação axonal. As lesões medulares causam um grande impacto na vida de seus portadores e de seus familiares. O uso das células tronco surgiu como uma alternativa viável ao tratamento das lesões medulares em humanos e animais. No entanto, apesar das tentativas terapêuticas em animais apresentarem resultados animadores, os ensaios clínicos realizados em humanos carecem de estudos mais aprofundados, e ainda não apresentaram resultados satisfatórios. O presente trabalho propôs a avaliação clínica do uso de células tronco da polpa dentária humana em cães com lesão medular crônica, e o uso das células tronco do epitélio olfatório de coelhos em coelhos com lesão medular induzida por hemissecção medular dorsal. Três cães foram submetidos à intervenção cirúrgica e avaliados através de teste comportamental e de ressonância magnética por imagem. Seis coelhos foram submetidos à técnica cirúrgica de hemissecção medular dorsal, e foram transplantados com células tronco do epitélio olfatório de coelhos e avaliados através de histologia e imunohistoquímica. As células-tronco do epitélio olfatório de coelhos foram rastreadas na medula espinhal dos animais 20 dias após a realização da terapia celular, confirmando o sucesso do transplante. A expressão da proteína fluorescente verde (GFP) através da imunohistoquímica comprovam o sucesso do transplante celular. O caso clínico canino um apresentou uma melhora clínica acentuada, pulando de um escore 4 para um escore de 8 em um curto espaço de tempo, mas não apresentou melhora nos exames de ressonância magnética. O caso clínico canino dois apresentou melhora clínica, embora a ressonância magnética mostrasse uma piora na situação da medula espinhal. E nosso caso clínico canino três apresentou mínima melhora clínica, sem alteração na imagem pré e pós operatória. Os dados obtidos com este estudo comprovam que a terapia celular com células tronco na lesão medular podem ser benéficas, no entanto ainda não representam uma cura para as lesões medulares crônicas. / The regeneration of damaged nerve cells of the central nervous system (CNS) is limited due to factors intrinsic to the own cell niche. The glial scar, the release of axonal growth inhibitors, and the phagocytic action of astrocytes are factors that limit this regeneration, deterring axonal restructuring. The spinal cord injuries cause a great impact on the lives of sufferers and their families. The use of stem cells has emerged as a viable alternative to the treatment of spinal cord injuries in humans and animals. However, despite attempts therapies in animals show encouraging results, clinical trials performed in humans require further study, and have not had satisfactory results. This paper proposed the clinical use of stem cells from human dental pulp in dogs with chronic spinal cord injury, and the use of stem cells from the rabbit olfactory epithelium in rabbits with spinal cord injury induced by dorsal hemisection. Three dogs underwent surgery and evaluated by behavioral test and magnetic resonance imaging. Six rabbits underwent surgical technique for spinal cord dorsal hemisection and were transplanted with stem cells from the olfactory epithelium of rabbits and evaluated by histology and immunohistochemistry. Stem cells of the olfactory epithelium of rabbits were traced in the spinal cord of animals 20 days after the completion of cell therapy, confirming the success of transplantation. Green fluorescent protein (GFP) tracked by immunohistochemical evidence the success of cell transplantation. The canine clinical case one presented a marked clinical improvement, jumping from a score of 4 to a score of 8 in a short time, but there was no improvement in magnetic resonance imaging. The canine clinical case two showed clinical improvement, although the MRI showed a worsening situation in the spinal cord. And our canine clinical case 3 showed minimal clinical improvement, no change in image pre-and postoperatively. The data obtained from this study show that cell therapy with stem cells in spinal cord injury may be beneficial, but still not a cure for chronic spinal cord injuries.

Lesões na medula espinhal atingem um grande número de pessoas, devido a traumas, doenças congênitas ou adquiridas. Para estes tipos de lesões não há cura e os indivíduos lesados medulares dependem de tratamento através de fisioterapia ou órteses que auxiliem na recuperação de possíveis funções perdidas. A Estimulação Elétrica Neuromuscular (EENM) tem sido pesquisada com essa proposta: reabilitar pessoas portadoras de lesão medular ou disfunções do aparelho locomotor. Muitos estudos já foram desenvolvidos na área de estimulação elétrica neuromuscular, avaliando a marcha, o ato de levantar-se ou outros movimentos. Um ponto em comum entre estes estudos é a preocupação com os efeitos fisiológicos da EENM, como por exemplo o gasto energético. Diante disto, o objetivo deste projeto foi avaliar os efeitos da EENM sobre o gasto energético de lesados medulares. Foi observado o consumo de oxigênio durante o repouso, a marcha e a recuperação. A avaliação proposta foi realizada por método indireto e as análises estatísticas foram realizadas através do teste ANOVA ONE WAY. Os resultados sugerem os voluntários tiveram recuperação fisiológica. Entretanto novas pesquisas são necessárias, com outras variáveis sendo avaliadas. / Lesions in the spinal cord affect a great number of individuals, either due to traumas or to congenital or acquired diseases. Such lesions are incurable, and the injured patients depend on physiotherapy or orthosis to aid in the recovery of lost functions. The Neuromuscular Electrical Stimulation (NMES) has been researched with this purpose: rehabilitating spinal cord injured patients, or those with motor system dysfunction. Several studies have already been developed in the field of neuromuscular electrical stimulation, assessing gait, the act of getting up or other everyday movements. All these studies bear something in common: the concern with the physiologic effects of NMES, such as the energy consumption. Hence, the objective of this project was to evaluate the effects of NMES on the energy cost of spinal injured patients. The consumption of oxygen was assessed during rest, gait and the recovery period. The proposed evaluation was made through indirect method, and the statistical analyses through the ANOVA ONE WAY test. The results to suggest that the volunteers had phisyological recovery. However, news reserchs there are needs, with others variable to be estimated.

This study explores potential therapeutic needs of people who have recently incurred a Spinal Cord Injury (SCI) and consequently live with an acquired disability. There are currently more people living with SCI than ever, yet there is still apparently little awareness or understanding of the complexity of the many potential psychological challenges caused by the injury. Despite disability being an inevitable part of existence, it is not consistently theoretically conceptualized other than to involve issues of power and vulnerability, and therapeutic literature relating to physical disability is scant. An inductive approach to the study was taken in order to focus on personal experiences of SCI, and more than one epistemological framework is mobilized in order to more comprehensively understand issues relating to disability and SCI. Using the (apparently conflicting) works of Foucault and Merleau-Ponty to inform a discourse analysis, both the cultural and historical social constructions, and the phenomenologically embodied aspects of disability are balanced to create a more holistic understanding of the experiences of acquired disability as a result of SCI. Seven participants were recruited for the study from an NHS specialist Spinal Injury Unit. Semi-structured interviews were conducted twice - once whilst participants were in-patients of the Unit, and once soon after they had been discharged. The main body of analysis is divided into three thematic sections: the Ecological - focusing on the roles of power relationships, institutions and culture through language and behavior, The Phenomenological - identifying the body as the primary site of 'knowing-in-the-world' and the implications to the sense of self of altered bodily experiences as a result of a new physicality, and The Existential - exploring how SCI can force a reconsideration of the possible significance or purpose(meaning) to be found in living. Trauma is acknowledged but not addressed as a primary focus, while the temporal element to the experience of SCI is identified. Focusing on the recently injured person's perspective at two significant points post-injury, this study aims to challenge the static concept of disability, and reconceptualise it as something experienced as fluid and context-dependent. The importance and affect of reflexivity in the study is also explored, as well as issues/implications of researcher positioning. The inter-relatedness of identified dominant themes is discussed in an attempt to illustrate the complex fluid interactions between SCI/acquired disability and individual life contexts. Identified themes are developed using critical disability theory, feminist literature, disability studies and Buddhist thought in order to advance understanding and conceptualisation of disability and the psychological experience of SCI. Education and reflexive awareness particularly regarding the machinations of widespread and embedded power relations relating to disability, as well as their consequences, are indicated as ethically necessary requirements (as an issue of social justice) for counselling psychologists to be able to practice appropriately, Ultimately, it is hoped that by investigating accounts of what affected individuals feel the dominant psychological challenges and difficulties are within their first year of injury, it may be possible for therapeutic services to become more effectively tailored to their specific needs.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O Traumatismo Raquimedular (TRM) à uma das principais causas de seqÃelas graves em paciente politraumatizado. ApÃs qualquer tipo de lesÃo raquimedular, a pessoa precisa enfrentar um processo de reabilitaÃÃo detalhado para que possa readquirir a capacidade de realizar suas atividades de vida, e viver de maneira independente. Este estudo teve como objetivo analisar a eficÃcia do cuidado de enfermagem fundamentado no Modelo de Enfermagem Roper-Logan-Tierney prestado a pessoas com lesÃo medular, bem como, conhecer a contribuiÃÃo da utilizaÃÃo de um modelo teÃrico para o cuidado direcionado a pessoas com lesÃo medular no domicÃlio. Trata-se de um estudo com abordagem qualitativa do tipo pesquisa de campo convergente-assistencial. Participaram do estudo trÃs pessoas (duas mulheres e um homem) com lesÃo raquimedular do tipo paraplegia, que estÃo incluÃdos no cadastro feito com os participantes das pesquisas realizadas pelo NÃcleo de Pesquisa e ExtensÃo em Enfermagem NeurolÃgica. O processo de investigar-cuidar se deu por meio de 10 visitas domiciliares (por sujeito), sendo os encontros fundamentados no Modelo de Enfermagem Roper-Logan-Tierney, utilizando o instrumento proposto pelas autoras, por meio do qual se abordou e identificou o desempenho das atividades de vida, destacando os problemas reais e potenciais, para ser traÃado o plano de cuidados e serem realizadas as intervenÃÃes necessÃrias, mantendo a constante avaliaÃÃo das respostas dos sujeitos. Para a obtenÃÃo das informaÃÃes foram utilizadas a observaÃÃo participante, a entrevista informal e a entrevista estruturada. No desenvolvimento dos processos assistenciais foram utilizados diagnÃsticos de enfermagem, NANDA, resultados de enfermagem, NOC, e intervenÃÃes de enfermagem, NIC. ApÃs detalhada sÃntese dos dados, foi dado significado a alguns achados provenientes do desempenho das atividades de vida pelos portadores de paraplegia, buscando contextualizÃ-los para uma ampliaÃÃo para a prÃtica assistencial dirigida a essa clientela. Com a anÃlise do comportamento dos trÃs sujeitos, o estudo mostra que a maior barreira para a efetividade do cuidado proposto à a dificuldade para mudanÃa de hÃbitos; entretanto, com a persistÃncia e a utilizaÃÃo de esclarecimentos e informaÃÃes necessÃrias obtÃm-se importantes resultados. Assim, ressalta-se a necessidade da promoÃÃo da auto-responsabilizaÃÃo da saÃde, para fortalecer a busca por mudanÃas de condutas. A utilizaÃÃo do modelo teÃrico Roper-Logan-Tierney no cuidado domiciliar, direcionado a esses portadores de paraplegia, contribuiu intensamente para a aquisiÃÃo do conhecimento sobre comportamentos e crenÃas em relaÃÃo a cada atividade de vida para que, diante disso, fosse feito o planejamento e implementado o cuidado. Com isso, o processo assistencial deixa de ser generalizado e passa a ser individualizado, trazendo melhores resultados. Foi possÃvel constatar a eficÃcia deste processo de investigar-cuidar, uma vez que foi notÃrio o benefÃcio resultante, por meio da conquista de maior independÃncia e capacidade de solucionar problemas pelos participantes do estudo e seus familiares. AlÃm disso, a utilizaÃÃo de um modelo teÃrico para o cuidado direcionado a pessoas com lesÃo medular no domicÃlio trouxe importantes contribuiÃÃes: proporcionou a sistematizaÃÃo da assistÃncia, facilitando a abordagem ao paraplÃgico e seu cotidiano e a eficÃcia do processo de cuidar proposto pela pesquisa; e promoveu uma fundamentaÃÃo teÃrica consistente para o desenvolvimento do cuidado. / The Spinal Cord Injury (SCI) is one of the main causes of serious sequels in trauma patient. After any type of spinal cord injury, the person will need to face a detailed process of rehabilitation, to reacquire the capacity to do its activities of life, and to live in independent way. The aim of this study was to analyze the effectiveness of the nursing care based on the Model of Nursing Roper-Logan-Tierney to people with spinal cord injury, as well as, knowing the contribution of the use of a theoretical model for the care directed to people with SCI in their home. It is a convergent-assistencial research. The participants of the study had been three people, two women and a man, with paraplegia, which are enclosed in a cadastre of participants of researches made by NUPEN. The process of investigating and taking care happened by means of 10 domiciliary visits (for each participant). The meetings were based on the Model of Nursing Roper-Logan-Tierney, using the instrument considered by the authors, in which it was approached and identified the performance of the activities of life, detaching the real and potential problems to be drawn the plan of cares up and to be done the necessary interventions, keeping the constant evaluation. The participant observation, the informal interview and the structuralized interview had been used for getting the information. In the development of the care process, it had been used nursing diagnosis, NANDA, nursing outcomes, NOC, and nursing interventions, NIC. After sum up in detail the data, I tried to give meaning to some information about the performance of the activities of life, trying to contextualize them for expanding for the care directed to people with spinal cord injury. When I was analyzing the behavior of the three participant of the study, I understood that the biggest barrier for the effectiveness of the considered care is the difficulty for change habits; however, with the persistence and the use of clarifications and necessary information important results are gotten. Therefore, I point out the importance of the promotion of the self-responsibility for health, to fortify the search for changes in behaviors. The use of the theoretical model Roper-Logan-Tierney in the domiciliary care directed to these clients contributed intensely for the acquisition of the knowledge about behaviors and beliefs related to each activity of life and up against this, planning and implementing the care. So, the care process leaves of being generalized and becomes individualized, causing better results. It was possible to detect the effectiveness of this process of investigating and taking care, once it was well-known the resultant benefit, by means of the conquest of more independence and more ability to solve problems for the participants of the study and its family. Moreover, the use of a theoretical model for the care directed to people with spinal cord injury in home brought important contributions: it provided the systematization for the assistance, facilitating the approach to the person with paraplegia and its daily and effectiveness of the process of taking care considered for the research; and promoted a consistent theoretical basis for the development of the care.

Made available in DSpace on 2015-04-22T22:14:17Z (GMT). No. of bitstreams: 1 Lionela Correa.pdf: 1636607 bytes, checksum: 83e46a87bd7d311464876eb93bb8b37d (MD5) Previous issue date: 2011-10-31 / Fundação de Amparo à Pesquisa do Estado do Amazonas / Quality of life theme is gaining interest in health in last decades. Because has proved a powerful tool for investigating and assessing patients, therapeutic interventions, and services in health. This study aimed to evaluate the quality of life of people with traumatic spinal cord injury based on the perception of the injured spinal cord. The subjects were individuals with SCI living in the Manaus city, which were affected by the injury in the period 2000 to 2010 and received at the Getulio Vargas University Hospital - HUGV. The instrument used to measure quality of life was the subject of the Portuguese version of the World Health Organization Quality of Life - Bref. A questionnaire was also applied to characterize socio-demographic subjects as well as knowing the causes of trauma and time of injury. It was examined the level of functional independence of the subjects through the Functional Independence Measure - FIM. Data analysis was performed using descriptive statistics and correlate the variables, age, gender, functional independence, socioeconomic status, time of injury, the sequel to the quality of life of individuals we used the Spearman correlation coefficient. The results showed a level of quality of life mean, and between the domains of quality of life those who had lower satisfaction among its facets were areas: social and environmental. In general the domain with the lowest score was the environmental field. When I checked whether there was correlation between the presenters that the only correlation was the age, the younger the better the assessment of quality of life perhaps better social integration on the part of the newest. We conclude that the factors that lead to an assessment of quality of life to a negative level are external factors, in other words, something that is not inherent in disability or deficit but inherent to environmental conditions. Keywords: quality of life, spinal cord injury, personal satisfaction. / O tema qualidade de vida vem ganhando interesse na área da saúde nas últimas décadas. Por se mostrar um ótimo indicador de satisfação em vários aspectos da vida para investigar e avaliar pacientes, intervenções terapêuticas, e serviços na área da saúde. Esse estudo teve por objetivo avaliar a qualidade de vida de pessoas com lesão medular traumática com base na percepção do lesado medular. Os sujeitos da pesquisa foram indivíduos com lesão medular traumática, residentes na cidade de Manaus, que foram acometidos pela lesão no período de 2000 a 2010 e que deram entrada no Hospital Universitário Getúlio Vargas - HUGV. O instrumento utilizado para mensurar a qualidade de vida dos sujeitos foi a versão em português do World Health Organization Quality of Life Bref. Também foi aplicado um questionário sócio demográfico para caracterizar os sujeitos bem como conhecer as causas do trauma e tempo de lesão. E foi averiguado o nível de independência funcional dos sujeitos através do questionário de medida de independência funcional MIF. A análise dos dados foi realizada por meio da estatística descritiva e para correlacionar as variáveis, idade, gênero, independência funcional, condição socioeconômica, tempo de lesão, sequela com a qualidade de vida dos sujeitos foi utilizado o coeficiente de correlação de Spearman. Os resultados apontaram para um nível de qualidade de vida médio, e entre os domínios de qualidade de vida os que apresentaram menor satisfação entre suas facetas foram os domínios: social e ambiental. De um modo geral o domínio que apresentou menor escore foi o domínio ambiental. Ao verificarmos se existia correlação entre as variáveis a única que apresentou correlação foi a idade, quanto menor a idade melhor a avaliação de qualidade de vida talvez por uma melhor inserção social por parte dos mais novos. Concluímos que os fatores que levam a uma avaliação de qualidade de vida para um nível negativo são fatores externos, ou seja, algo que não é inerente a deficiência ou déficit, mas inerente às condições ambientais

As doenças de disco intervertebrais (DDIV) representam a maior parte de atendimentos neurológicos e são responsáveis pela maioria dos casos de paralisia em cães. Os tratamentos utilizados atualmente não demonstram resultados satisfatórios em pacientes com manifestações neurológicas mais graves. A fim de promover recuperação nervosa e motora, além de melhora na qualidade de vida, o presente trabalho objetivou criar um protocolo, através de um ensaio duplo cego, associando cirurgia descompressiva e transplante alogênico de células-tronco (CT) derivadas da membrana amniótica em cães com DDIV crônica. As mesmas células já foram caracterizadas anteriormente como mesenquimais fetais e apresentaram-se seguras para aplicação. Foram selecionados oito cães, onde quatro já passaram por cirurgia e receberam três aplicações epidurais de células-tronco. Os outros quatro animais foram submetidos à cirurgia descompressiva e divididos aleatoriamente (teste duplo cego) em dois grupos: \"cirurgia + placebo\", o qual recebeu apenas solução fisiológica; e \"cirurgia + CT\", que recebeu a terapia celular. Durante o procedimento cirúrgico, foi realizado a aplicação por gotejamento sobre a lesão, e após quinze e quarenta e cinco dias foram realizadas outras duas aplicações, via epidural. Os animais passaram por acompanhamento quinzenal e foram reavaliados três meses após o procedimento cirúrgico, através de exames funcionais e ressonância magnética. Alguns animais apresentaram melhora neurológica significativa, como a recuperação da nocicepção e capacidade de se manter em estação. Apesar da necessidade de mais estudos, até o presente momento, a terapia celular apresentou-se factível e sem efeitos prejudiciais aos animais. / Intervertebral disc (IVD) diseases represent the majority of neurological attendance and are responsible for the most cases of paralysis in dogs. Treatments currently used do not show satisfactory results in patients with more severe neurological manifestations. In order to promote nerve and motor recovery, as well as improve quality of life, the present study aims to create a protocol, using double-blind test method, associating spinal decompression surgery and allogeneic transplantation of amniotic membrane-derived stem cells (AMSCs) in dogs with chronic IVD diseases. Those were previously characterized as fetal mesenchymal cells and were safe for application. Eight dogs were selected, where four have already gone through surgery and received 3 epidural applications of stem cells. The other four animals were submitted to spinal decompression surgery and randomly divided into two groups (double blind test): \"surgery + placebo\", which received only physiological solution; and \"surgery + AMSCs\", which receive cell therapy. During the surgical procedure, a drip application was performed on the lesion and after fifteen and forty five days another two applications were made via epidural. Animals were monitored biweekly and were reassessed three months after surgery, by functional tests and magnetic resonance exams. Some animals presented significant neurological improvement, such as the recovery of nociception and ability to remain on station. Despites the need further studies, until the present moment, cell therapy has been feasible and has no harmful effects on animals.

The loss of physical activity after a spinal cord injury results in musculoskeletal deterioration and metabolic dysfunction. Rehabilitation often overlooks the importance of physical activity in the paralyzed limbs for systemic metabolic health. There is a need for safe, feasible exercise interventions to increase physical activity levels in the paralyzed limbs of people with chronic paralysis that have severe musculoskeletal loss. The goal of this work is to 1) develop a gene expression signature after a single dose and long term training using a high force exercise in people with an acute spinal cord injury; 2) develop a novel low force exercise intervention using electrical muscle stimulation to limit force production and increase routine physical activity for chronically paralyzed human skeletal muscle; 3) determine the gene expression signature after a single dose of this novel low force exercise in people with long term paralysis; 4) develop a dose estimate of this low force exercise needed to initiate a phenotype transformation of chronically paralyzed skeletal muscle. The major findings of this research are 1) a single dose of high force exercise increases the expression of key regulatory genes needed for the transformation of paralyzed skeletal muscle observed after long term training; 2) our novel low force exercise intervention challenges chronically paralyzed muscle but not non-paralyzed muscle; 3) a single dose of low force exercise increases the expression of key regulatory genes needed to improve skeletal muscle health; 4) a dose of at least 4 days per week of our low force exercise is needed to initiate a phenotype transformation of chronically paralyzed skeletal muscle. Together, this work supports the use of a low force exercise intervention for people with long term spinal cord injury and establish the need for future work assessing effects of our low force exercise on the systemic health and quality of life of people with long term spinal cord injury.

The corticospinal tract (CST), which carries commands from the cerebral cortex to the spinal cord, is vital to fine motor control. Spinal cord injury (SCI) often damages CST axons, causing loss of motor function, most notably in the hands and legs. Our preliminary work in rats suggests that CST circuitry is complex: neurons whose axons project to the lower cervical spinal cord, which directly controls hand function, also send axon collaterals to other locations in the nervous system and may engage parallel motor systems. To inform research into repair of SCI, we therefore aimed to map the entire projection pattern, or “connectome,” of such cervically-projecting CST axons. In this study, we mapped the corticospinal connectome of the Rhesus macaque - an animal model more similar to humans, and therefore more clinically relevant for examining SCI. Comparison of the Rhesus macaque and rat CST connectome, and extrapolation to the human CST connectome, may improve targeting of treatments and rehabilitation after human SCI. To selectively trace cervically-projecting CST motor axons, a virus encoding a Cre-recombinase-dependent tracer (AAV-DIO-gCOMET) was injected into the hand motor cortex, and a virus encoding Cre-recombinase (AAV-Cre) was injected into the C8 level of the spinal cord. In this intersectional approach, the gCOMET virus infects many neurons in the cortex, but gCOMET expression is not turned on unless the nucleus also contains Cre-recombinase, which must be retrogradely transported from axon terminals in the C8 spinal cord. Thus, gCOMET is only expressed in neurons that project to the C8 spinal cord, and it proceeds to fill the entire neuron, including all axon collaterals. Any gCOMET-labeled axon segments observed in other regions of the nervous system are therefore collaterals of cervically-projecting axons. gCOMET-positive axons were immunohistochemically labeled, and axon density was quantified using a fluorescence microscope and Fiji/ImageJ software. Specific regions of interest were chosen for analysis because of their known relevance in motor function in humans, and for comparison to results of a similar study in rats. Results in the first monkey have revealed both similarities and differences between the monkey and rodent CST connectome. Analyses of additional monkeys are ongoing. The final results will provide detailed information about differences between rodent and primate CST, will serve as a baseline for examining changes in the CST connectome after SCI, and will provide guidance for studies targeting treatment and functional recovery after SCI.

Vital autonomic and cardiovascular functions are susceptible to dysfunction after spinal cord injury (SCI), with cardiovascular dysregulation contributing to morbidity and mortality in the SCI population. Autonomic dysreflexia (AD) is a condition that develops after injury to the sixth thoracic spinal segment or higher and is characterized by potentially dangerous and volatile surges in arterial pressure often accompanied with irregular heart rate, headache, sweating, flushing of the skin, and nasal congestion. These symptoms occur in response to abnormal outflow of sympathetic activity from the decentralized spinal cord typically triggered by noxious, yet unperceived nociceptive stimulation beneath the level of lesion. Maladaptive plasticity of primary afferents and spinal interneurons influencing sympathetic preganglionic neurons is known to contribute to the development of AD. However, there are currently no treatments capable of targeting this underlying pathophysiology. The goal of this work was to test pharmacological agents for their potential to modify intraspinal plasticity associated with AD in order to prophylactically prevent the development of this condition altogether. We first tested whether the drug rapamycin (RAP), a well-studied inhibitor of the growth promoting kinase “mammalian target of rapamycin” (mTOR), could prevent aberrant sprouting of primary c-fiber afferents in association with reduced indices of AD severity. Naïve and T4-transected rats undergoing 24/7 cardiovascular monitoring were treated with rapamycin (i.p.) for 4 weeks before tissue collection. RAP attenuated intraspinal mTOR activity after injury, however it also caused toxic weight loss. RAP treated SCI rats developed abnormally high blood pressure both at rest and during colorectal distension (CRD) induced AD, as well as more frequent bouts of spontaneous AD (sAD). These cardiovascular alterations occurred without altered intraspinal c-fiber sprouting. Our finding that rapamycin exacerbates cardiovascular dysfunction after SCI underscores the importance of screening potential pharmacological agents for cardiovascular side effects and suggests that the mTOR pathway plays a limited or dispensable role in c-fiber sprouting after SCI. We next examined the effects of the antinociceptive drug gabapentin (GBP) on AD development. Our previous work demonstrated that a single acute administration of GBP can reduce the severity of AD. The mechanism of action, however, remains unclear. Emerging evidence suggests that GBP may act by blocking de novo synaptogenesis. We investigated whether continuous GBP treatment could attenuate the development of AD by modifying synaptic connectivity between primary afferents and ascending propriospinal neurons. SCI rats were treated with GBP every six hours for four weeks. We found that GBP reduced blood pressure during CRD stimulation and prevented bradycardia typically observed during AD. However, GBP treated rats also had a higher sAD frequency and failed to return to pre-injury body weight. Moreover, SCI reduced the density of putative excitatory (VGLUT2+) and inhibitory (VGAT+) synaptic puncta in the lumbosacral cord, although GBP did not alter these parameters. Our results suggest that continuous GBP treatment alters hemodynamic control after SCI and that decreased synaptic connectivity may contribute to the development of AD. These studies demonstrate the need for further research to better understand the cellular signaling driving maladaptive plasticity after SCI as well as the complex and dynamic changes in intraspinal synaptic connectivity contributing to the development of AD. Moreover, GBP treatment may offer clinical benefit by reducing blood pressure during AD, however the optimal dosage must be identified to avoid undesired side-effects.