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TARGETING MALADAPTIVE PLASTICITY AFTER SPINAL CORD INJURY TO PREVENT THE DEVELOPMENT OF AUTONOMIC DYSREFLEXIAEldahan, Khalid C. 01 January 2019 (has links)
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.
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Facilitators and Barriers to Physical Activity Among People With Spinal Cord InjuryRichardson-Smith, Laura Nicole 01 January 2016 (has links)
Research has shown that people with physical disabilities are at risk for developing secondary health conditions. Many of these secondary health conditions may be reduced by engaging in physical activity, yet people with physical disabilities are less likely to participate in physical activity. Information gaps remain regarding facilitators and barriers to physical activity. The purpose of this phenomenological study was to understand the experiences with physical activity among adults with a spinal cord injury (SCI). Research questions asked were about exercise experiences, barriers and facilitators, and the role of the natural and social environment. The theoretical framework used was the theory of planned behavior, in which attitudes and perceived advantages and disadvantages to performing a behavior are considered. In-depth interviews were conducted with 10 adults, 18 years of age and older, who have an SCI that requires the use of a wheelchair. Interviews were transcribed verbatim and analyzed thematically by identifying key phrases, determining recurring phrases, and grouping codes into themes. NVivo, a qualitative software, aided in the analysis. The participants in this study faced many obstacles, including physical and social barriers. Despite these barriers, participants recognized the importance of physical activity and identified factors that encouraged exercise. The implications for positive social change from this research include a better understanding among healthcare professionals working with people with disabilities and disability advocates of the experiences people with an SCI have when exercising and the potential to minimize the barriers to physical activity in an effort to reduce related secondary health conditions.
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Understanding the Lived Experiences of Women with Spinal Cord Injury who Undergo Urinary Diversion SurgeryDhillon, Sukhpinder K. 01 January 2015 (has links)
Following spinal cord injury (SCI), bladder management is of primary importance. As an activity of daily living (ADL), it affects community integration and quality of life (QOL). Women with SCI have neurogenic bladders that require self-catheterization, but they are unable to catheterize the native urethra, thus making bladder management physically and emotionally challenging. The purpose of this study was to understand the experiences of women with SCI who undergo urinary diversion surgery for bladder management. Qualitative data were collected using semistructured interviews from 10 women with SCI after urinary diversion surgery for bladder management. Qualitative Nvivo analysis of interview data was based on cognitive adaptation theory, which emphasizes adaptation to life-threatening events. Analysis showed improved quality of life among these 10 women, with improvements in independence, convenience, aesthetics, confidence, and sexuality. The women's lived experiences also showed enhanced privacy, dignity, normalcy, and safety. The lack of awareness in health care workers to offer this procedure was universally highlighted by participants. The social change implications include the need to advocate for women with SCI with bladder management needs who are unaware of this surgery option. Understanding the bladder management needs of women with SCI may help this population make choices for a better quality of life.
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A theory of calcium dynamics in generating force and low-frequency fatigue in paralyzed human soleusConaway, Matthew James 01 July 2010 (has links)
Paralyzed muscle fatigues more quickly than intact muscle. The reason for this difference is currently unknown. This work will bridge this gap in knowledge by evaluating the predictive abilities of higher-resolution closed-form mathematical models of muscle force and fatigue. Knowledge garnered from this effort will suggest possible mechanisms for the differences in fatiguability of muscle in different states of health.
The hypothesis to be tested is that the concept missing from present models, and thus the present understanding of the physiology, is the dynamic behavior of divalent calcium (Ca2+) during induced muscle contraction. If the behavior of Ca2+ can be understood as a Riccati-Bass diffusion process, muscle force and low-frequency fatigue in paralyzed muscle can be more accurately predicted over the time course of response to neuromuscular electrical stimulation. The abilities of existing mathematical models to predict force and low-frequency fatigue are compared to the predictive abilities of new models that include the Riccati-Bass equation.
There are several major findings of this study. First, it was found that the structure of the Conaway models better predicts force and low-frequency fatigue than do the Ding models. Second, the cross-bridge friction is the most influential factor in generating force in fresh muscle at frequencies greater than 5 pps. Finally, the calcium leak current is most influential in low-frequency fatigue in paralyzed muscle. It is concluded that the process of muscle fatigue occurs as calcium channel remodeling and inactivation of excitation-contraction coupling from ionic crowding accelerate with every additional contraction.
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Behavioural and protective factors contributing to the risk and vulnerability to HIV/AIDS among individuals with spinal cord injuries in South AfricaLloyd, Jacobus January 2019 (has links)
Philosophiae Doctor - PhD / HIV/AIDS has made a huge impact on human development and sexual reproductive habits in this century in the world and especially in sub-Saharan Africa. It has only recently been acknowledged that HIV/AIDS has an equal if not greater effect on or threat to people with disabilities. Survivors of traumatic spinal cord injury (TSCI) with resultant disability are incorrectly believed to be sexually inactive, unlikely to use drugs or alcohol and at less risk of violence or rape than their non-disabled peers. This group can thus be described as economically, educationally and socially disadvantaged, which in itself, suggest that they are a high-risk group for HIV infection. The overall aim of this study is to examine the factors that could contribute to the risk and vulnerability to HIV/AIDS among individuals with spinal cord injuries in South Africa. The specific objectives of the study are to assess the behavioral and protective factors that could contribute to risk and vulnerability to HIV infection among individuals and spinal cord injuries; and to explore the socio-cultural issues that might increase individuals with spinal cord injuries’ vulnerability to HIV/AIDS. The design of this study was a mixed methods design, particularly the sequential explanatory strategy was used will used in this study. The study was conducted in four (4) conveniently selected provinces (highest prevalence of SCI). The Quad-Para Association of South Africa’s (QASA) provincial databases was used to invite individuals with SCI to participate in the study. Data for quantitative part of the study was collected by means of self-administered questionnaires. The questionnaire consisted of various sections requesting for information on: Demographics; HIV-Knowledge (HIV- KQ-18); Sexual behaviours; Sexual communication and negotiation skills; Self-efficacy to refuse sex. Separate binary logistics analysis was done to assess which of the selected factors are associated with risky sexual behaviour. The forced entry method approach was used to determine which of these factors have the greatest productive power to predict sexual risk behaviour. No “a priori” sample size was developed for the qualitative part, but participants were recruited until saturation has been reached of all the categories. Consenting participants were visited by the researcher for data collection in the environment indicated by the participant. Permission to conduct the study was obtained from the Research Ethics Committee at the University of the Western Cape (UWC). The study was conducted according to ethical practices pertaining to the study of human subjects as specified by the UWC and Faculty of Community and Health Sciences Research Ethics Committee of the UWC.
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The Development of an Adaptive Driving SimulatorTudor, Sarah Marie 12 March 2015 (has links)
The ability to drive a car is an important skill for individuals with a spinal cord injury to maintain a high quality of life, particularly their freedom and independence. However, driving with a physical disability often requires the installation of an adaptive driving system to control steering, gas, and braking. The two main types of adaptive driving controls are mechanical and electrical, also known as drive by wire (DBW). DBW controls work by converting electric signals to mechanical actuators. Driving simulators are useful tools for adaptive driving systems because they allow users to test different control devices, to practice driving without the dangers of being on the road, and can be used as a safe way to evaluate disabled drivers. This study focused on the development of a dynamic driving simulator using DBW controls because many studies focus on mechanical controls and not DBW controls and often use static simulators.
The simulator was developed using the Computer Assisted Rehabilitation Environment (CAREN) virtual reality system. The CAREN system (Motek Medical, Amsterdam, Netherlands) includes a six degree of freedom (DOF) motion base, an optical motion capture system, a sound system, and a 180-degree projection screen. The two DBW controls, a lever device to control the gas and brake and a small wheel device to control steering, sent an electric signal to a Phidget microcontroller board, which interfaced with the CAREN system. Several different driving scenarios were created and imported into CAREN's D-Flow software. A program was developed in D-Flow to control the scene and motion of the platform appropriately based on the DBW controls via the Phidget. The CAREN system dynamically controlled the motion platform based on the user's input. For example, if the user applied the brake suddenly, the user felt a deceleration from the motion platform moving backwards. Human testing was performed and through the use of a survey, feedback about the system was obtained. Changes were made to the simulator using the feedback obtained and further testing showed that those changes improved the simulator. The driving simulator showed the capability to provide dynamic feedback and, therefore, may be more realistic and beneficial than current static adaptive driving simulators. The dynamic adaptive driving simulator developed may improve driving training and performance of persons with spinal cord injuries. Future work will include more human testing. The dynamic feedback provided through the system's moving platform and virtual camera movement will be optimized in order to perform similarly to a real car. Testing will also be completed with and without the dynamics from the moving platform to see how this type of feedback affects the user's driving ability in the virtual environment.
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Applying Modeled Hemi-Ellipsoids to the Study of Pressure Distribution in Normal and Paraplegic Seated SubjectsBillington, Alicia 24 June 2014 (has links)
The three goals of this research were to investigate how normal subjects move while seated, how paraplegic patients move while seated, and whether seated movements can be modeled using a hemi-ellipsoid shape. Pressure readings were recorded at 11 Hz using a 36 by 36 sensor pressure map by XSENSOR. Subjects were instructed to move or perform pressure relief as they normally would while seated. Analysis was performed using Microsoft Excel with Solver and Matrix.xla add-ins and automated with VBA code. Major movements and time intervals between movements were calculated by locating the area of maximum pressure on each hemi-buttock for 20 normal and 6 paraplegic subjects. Statistical analysis revealed movements followed a normal distribution while time intervals followed a lognormal distribution. For both the normal (p=0.041) and paraplegic groups (p=0.007) the number of movements significantly increased from the first hour of recording to the second hour. The time interval between major movements decreased but not significantly for neither the normal subjects nor the paraplegics. No significant differences were identified between the normal and paraplegic groups over the first hour or second hour for number of movements or time intervals. Time series analysis with plotting, trend lines, ARIMA, and periodograms did not reveal patterns in the data. Preference for a side was shown. Next, all areas of identified major movements for one subject and one frame for each of the paraplegic patients were modeled as a hemi-ellispoid shape using minimization with Solver. Eigenvalues were calculated in order to obtain the lengths of the x, y, and z axis of the hemi-ellipsoid with an average error of 39.87% for the normal subject and an error range of 5.10% to 2701.81% for the paraplegic patients.
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You're pretending, you don't need a wheelchair' - children and adolescents with spinal cord injuryLeeds, Marilyn June January 2001 (has links)
This thesis examines the requirements of children and adolescents with severe spinal cord injuries. The requirements are expressed by the parents of the children and by adolescents and are in contrast to official views of their 'needs'. There is no literature on the needs of these children and adolescents. The thesis thus begins with a examination of the literature on the needs of people with disabilities and people with spinal cord injury. Proponents of the social model of disability, which is based on the experiences of people with disabilities, contend that the main requirements of people with disabilities is ending their social marginalisation, and it is hypothesised that the requirements of the children and adolescents will be related to ending social marginalisation. Open-ended unstructured interviews with parents, parents and adolescents and adolescents alone ( a total of 20 interviews) provided data for analysis. Analysis of the data shows that the requirements of the children and adolescents, like adults with spinal cord injuries, differ from those of people with disabilities in that there are important concerns in addition to marginalisation.
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Evidence-based interventions by hospital social workers for patients with spinal cord injuriesKusec Fredriksson, Ruth January 2005 (has links)
<p>Some 120 to 150 people per year, in Sweden, injure their spinal cord in an often traumatic accident. During the initial trimester in a university hospital there are several issues arising for the patients, not only the fact that they suddenly cannot walk. The aim of this undergraduate thesis is to provide a review of selected literature on evidence-based interventions by hospital social workers for spinal cord injured. The method used in the thesis is database searches. Fourteen articles were included in the review. These articles have been divided into the categories: coping and interventions. Research shows that spinal cord injured have an increased risk of anxiety and depression. The most important findings were that spinal cord injured in both Sweden and Finland are dissatisfied with the societal services, that a spinal cord injury does not necessarily lead to anxiety and depression and that there are even positive outcomes of a spinal cord injury. Social and societal services are important in the adjustment process for spinal cord injured. Psychological interventions based on cognitive-behaviour therapy have been proven effective in the care of spinal cord injured.</p>
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Motor unit recruitment by intraspinal microstimulation and long-term neuromuscular adaptationsBamford, Jeremy, Andrew 11 1900 (has links)
Spinal cord injury is a devastating neurological disorder partially characterized by a loss of motor function below the lesion. The dramatic loss of activity results in muscle atrophy and slow-to-fast transformation of contractile elements, producing smaller, weaker and more fatiguable muscles. Functional electrical stimulation (FES), has been proposed in order to induce muscular activity and reverse these changes. FES has primarily been applied in the periphery, either at the surface or implanted in or around a nerve or muscle. Although this can excite nervous tissue and produce muscular contractions, these systems often produce reversed recruitment of motor units leading to inappropriate force generation and increased fatigue.
We applied intraspinal microstimulation (ISMS) through fine microwires implanted into the spinal cord of rats. Electrical stimulation through these microwires caused contractions of the quadriceps muscles in both acute and chronically spinalized animals. We showed that muscle recruitment is significantly more gradual with ISMS in intact rats compared to that produced by a standard nerve cuff. Our results further showed that this was due to preferential activation of fatigue resistant muscle fibers.
Given this more orderly recruitment of motor units by ISMS, we tested the muscle phenotypes produced by ISMS or nerve cuffs after chronic stimulation. Surprisingly, over a 30 day stimulation period the quadriceps muscles chronically activated by either daily ISMS or nerve cuff stimulation underwent similar fast-to-slow transformations in fiber type and functional properties. This indicates that the recruitment order of motor units does not play the only role in determining the muscle phenotype. Other factors such as the total daily time of activity may be critically important to the phenotypic outcome of skeletal muscle.
Finally, we demonstrated that quadriceps force recruitment by ISMS was unchanged following the 30 day stimulation period. In addition, 30 days of chronic ISMS did not cause observable damage in the spinal cord beyond that incurred by the implantation of sham microwires. These studies advance our understanding of the force recruitment properties, neuromuscular plasticity and damage incurred by ISMS and move us closer to developing a clinically viable ISMS procedure.
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