Spinal cord injuries can cause the catastrophic loss of motor and sensory function. The neurological deficits that result are the consequence of not only the primary injury to the spinal cord, but also a complex milieu of secondary pathological processes that are now beginning to be understood. The major mechanisms that underlie this secondary pathology include vascular disruption, ischemia, oxidative stress, excitotoxicity, and inflammation. In light of this, the fact that this secondary pathology occurs after the initial impact makes it potentially amenable to therapeutic intervention. Pharmacotherapies may attenuate some of these processes and minimize secondary damage. Some of the promising treatments that are emerging for acute spinal cord injury are drugs that are already used by physicians for the treatment of unrelated diseases. These drugs, which have already been established to be safe for humans, offer the unique advantage over other novel therapeutic interventions that have yet to be tested in humans. This would save a tremendous amount of time and money needed for human safety studies, if considered as a treatment for spinal cord injury. Examples of such drugs include minocycline (an antibiotic), erythropoietin (a recombinant hormone used to treat anemia), and statins (a popular class of blood cholesterol reducers), all of which have demonstrated the ability to attenuate the various pathophysiological processes initiated after trauma to the central nervous system. In a series of studies, erythropoietin, darbepoetin, atorvastatin, simvastatin, and minocycline were all evaluated for their ability to improve neurologic recovery in a clinically relevant model of spinal cord injury. My experiments revealed that erythropoietin, darbepoetin, atorvastatin and minocycline did not significantly improve neurological recovery. These negative results were in stark contrast to the positive findings which had been published in the literature suggesting that differences in experimental models and methodology influence the neuroprotective efficacy of these drugs. Simvastatin, on the other hand, demonstrated significant improvements in locomotor and histological outcomes. Although this is indeed exciting, the results were modest at best. My results highlight the need for further preclinical work on the above treatments to refine and optimize them prior to proposing them for human testing.

Research has shown that exposure to just 6 minutes of uncontrollable shock 24 hours following contusion injury impairs locomotor recovery and leads to greater tissue loss at the injury epicenter. Uncontrollable shock is known to elevate corticosterone levels in intact rats and corticosterone exacerbates cell death in the hippocampus following injury, suggesting the effects may be related to a stress-induced release of corticosterone. Uncontrollable shock also affects other indices of stress including, spleen weight and norepinephrine, and has been shown to elevate pro-inflammatory cytokines. The present experiments were designed to assess whether uncontrollable shock has similar effects after contusion injury. Experiment 1 examined whether injury itself produced a stress response. Subjects received anesthesia alone, a laminectomy, or a contusion injury. Twenty-four hours later, they were restrained for 6 minutes and blood was collected from the leg. They were sacrificed 24 hours later and spleens were weighed, and plasma corticosterone and norepinephrine were assessed using ELISAs. IL-1! and IL-6 levels at the injury site were also measured using an ELISA. Contusion injury had no impact on any of the biological outcomes. For Experiment 2, subjects received 6 minutes of uncontrollable tailshock or an equivalent amount of restraint. Subjects were sacrificed 6, 24, 72, or 168 hours later. Uncontrollable shock caused a decrease in spleen weight and increased plasma corticosterone within 24 hours. Increases in IL-1! and IL-6 were also seen. Morphine was used in Experiment 3 to block the “psychological” component of uncontrollable shock. Subjects received morphine (20 mg/kg; i.p.) or saline 30 minutes prior to uncontrollable shock and were sacrificed 24 hours later. Morphine did not prevent the consequences of uncontrollable shock and, in some cases, potentiated its effects. The effect of controllability was examined in Experiment 4. After receiving a contusion injury, subjects received either controllable (master) or uncontrollable (yoked) legshock over the course of 2 days. A third group served as unshocked controls. Master subjects did not differ from yoked subjects on any of the biological outcomes measured. Unshocked subjects, however, exhibited an increase in corticosterone, IL-6, and blood monocytes.

Spinal cord injuries can cause the catastrophic loss of motor and sensory function. The neurological deficits that result are the consequence of not only the primary injury to the spinal cord, but also a complex milieu of secondary pathological processes that are now beginning to be understood. The major mechanisms that underlie this secondary pathology include vascular disruption, ischemia, oxidative stress, excitotoxicity, and inflammation. In light of this, the fact that this secondary pathology occurs after the initial impact makes it potentially amenable to therapeutic intervention. Pharmacotherapies may attenuate some of these processes and minimize secondary damage. Some of the promising treatments that are emerging for acute spinal cord injury are drugs that are already used by physicians for the treatment of unrelated diseases. These drugs, which have already been established to be safe for humans, offer the unique advantage over other novel therapeutic interventions that have yet to be tested in humans. This would save a tremendous amount of time and money needed for human safety studies, if considered as a treatment for spinal cord injury. Examples of such drugs include minocycline (an antibiotic), erythropoietin (a recombinant hormone used to treat anemia), and statins (a popular class of blood cholesterol reducers), all of which have demonstrated the ability to attenuate the various pathophysiological processes initiated after trauma to the central nervous system. In a series of studies, erythropoietin, darbepoetin, atorvastatin, simvastatin, and minocycline were all evaluated for their ability to improve neurologic recovery in a clinically relevant model of spinal cord injury. My experiments revealed that erythropoietin, darbepoetin, atorvastatin and minocycline did not significantly improve neurological recovery. These negative results were in stark contrast to the positive findings which had been published in the literature suggesting that differences in experimental models and methodology influence the neuroprotective efficacy of these drugs. Simvastatin, on the other hand, demonstrated significant improvements in locomotor and histological outcomes. Although this is indeed exciting, the results were modest at best. My results highlight the need for further preclinical work on the above treatments to refine and optimize them prior to proposing them for human testing.

Spinal cord injuries can cause the catastrophic loss of motor and sensory function. The neurological deficits that result are the consequence of not only the primary injury to the spinal cord, but also a complex milieu of secondary pathological processes that are now beginning to be understood. The major mechanisms that underlie this secondary pathology include vascular disruption, ischemia, oxidative stress, excitotoxicity, and inflammation. In light of this, the fact that this secondary pathology occurs after the initial impact makes it potentially amenable to therapeutic intervention. Pharmacotherapies may attenuate some of these processes and minimize secondary damage. Some of the promising treatments that are emerging for acute spinal cord injury are drugs that are already used by physicians for the treatment of unrelated diseases. These drugs, which have already been established to be safe for humans, offer the unique advantage over other novel therapeutic interventions that have yet to be tested in humans. This would save a tremendous amount of time and money needed for human safety studies, if considered as a treatment for spinal cord injury. Examples of such drugs include minocycline (an antibiotic), erythropoietin (a recombinant hormone used to treat anemia), and statins (a popular class of blood cholesterol reducers), all of which have demonstrated the ability to attenuate the various pathophysiological processes initiated after trauma to the central nervous system. In a series of studies, erythropoietin, darbepoetin, atorvastatin, simvastatin, and minocycline were all evaluated for their ability to improve neurologic recovery in a clinically relevant model of spinal cord injury. My experiments revealed that erythropoietin, darbepoetin, atorvastatin and minocycline did not significantly improve neurological recovery. These negative results were in stark contrast to the positive findings which had been published in the literature suggesting that differences in experimental models and methodology influence the neuroprotective efficacy of these drugs. Simvastatin, on the other hand, demonstrated significant improvements in locomotor and histological outcomes. Although this is indeed exciting, the results were modest at best. My results highlight the need for further preclinical work on the above treatments to refine and optimize them prior to proposing them for human testing. / Science, Faculty of / Zoology, Department of / Graduate

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Magister Scientiae (Physiotherapy) - MSc(Physio) / The distressing event of Spinal Cord Injury (SCI) leads to complete or incomplete injury, and results in many complications such as such as neurogenic shock, cardiovascular disease, temperature regulatory problems, respiratory complications, dysphagia, thromboembolism, and pressure ulcers amongst others. These complications limit the individual’s functioning and participation. Participation is fruitful and meaningful when you are actively involved in a specific activity. To understand the lack of participation within a specific setting, it is important to know what the limitations in activities are, and what causes these limitations. The goal of rehabilitation should be to reintegrate patients back into the community so that they can fulfil their roles. Aim: The aim of the study was (1) To determine included participants’ socio-demographic and injury characteristics; (2) To describe healthcare services received by people living with long-term Traumatic Spinal Cord Injury (TCSI) over the past 12 months; (3) To determine the point prevalence of common activity limitations of survivors of TSCI four years after injury; (4) To determine the point prevalence of participation restrictions of survivors of TSCI four years after injury; and (5) To determine factors associated with activity limitations and selected participation restrictions four years after injury.

Thesis (MSc. (Clinical Psychology)) -- University of Limpopo (Medunsa Campus), 2012 / Spinal cord injury (SCI) is believed to place the individual at a high risk of psychological turmoil. This study explored the subjective experiences of SCI persons, by exploring the psychological effects of SCI at Dr. George Mukhari Hospital. To achieve this, the primary objectives of the study were to; explore the psychological effects faced by SCI individuals; and explore the impact of these effects in their lives and well-being. Participants included eight SCI persons who were in the rehabilitation programme. A qualitative exploratory enquiry approach was utilised, by conducting semi-structured interviews. Data was analysed using a thematic analysis. Two main themes emerged: the psychological effects of SCI and impact of these effects on the well-being of the person. The psychological effects faced by SCI persons were linked to diminished independence, intrapersonal changes, altered interpersonal relationships and emotional disturbance. The psychological effects seemed to be devastating to the optimal functioning of the participants. The impact of these effects was perceived as life changing. The impact of the psychological effects of SCI was linked to psychological adjustment. Psychological adjustment referred to the variety coping strategies adopted by participants and their perceptions post injury. The coping strategies included effective and ineffective coping strategies. Most participants struggled as they attempted to make sense of the effect of SCI. Life post- injury was perceived with mixed emotions that of being hopeful and on other hand fearful; hopeful that their (participants) condition would change for the better, yet fearful as to what if it does not. As to deal with the devastating impact of SCI, participants engaged in a process of reconstructing the self, coming to terms with disability, and striving for maintaining a positive outlook post-SCI. v In conclusion, understanding how SCI persons view themselves post-injury is a prerequisite to the development of appropriate SCI psychological strategies to facilitate optimal functioning. Thus psychological adjustment remains critical in determining the rehabilitation process post injury.

This dissertation presents the prediction of quality of life (QoL), composed of by life satisfaction and self-perceived health status, across 5 years post a spinal cord injury (SCI) hospital discharge. Predictor variables of functional independence, pain, and family satisfaction, as mediated by environmental accessibility are examined. Environmental accessibility is conceptualized as being composed of mobility and social integration. Data are a subset from a longitudinal study of adjustment following disability. Two models were examined in order to predict QoL, Model 1 (Life Satisfaction) and Model 2 (Self-Perceived Health Status). Results from this study were obtained by testing models using path modeling. Evaluation indices suggest good to adequate model fit, CFI, RMSEA, and SRMR for Model 1 and Model 2. In Model 1, results indicated that mobility and social integration, components of environmental accessibility, mediated the relationship between functional independence and life satisfaction (beta = 0.243, p = 0.009 and beta = 0.120, p = 0.038, respectively). In Model 2, the component of mobility of environmental accessibility mediated the relationship between functional independence and self-perceived health status (beta = 0.288, p = 0.002). Results indicate that access to the environment is an important predictor of life satisfaction and perceived health status five years after medical discharge for a traumatically-acquired SCI. These factors of environmental access ? mobility and social integration ? appear to be more important determinants of quality of life post-SCI than functional impairment or the presence of pain. Programs that enhance mobility and social integration following return to the community following SCI may be indicated. Furthermore, given that the construct of environmental accessibility is relatively new, studies that examine this construct are needed in order to better understand how it is best conceptualized.

Spinal Cord Injury (SCI) often causes cell death, demyelination, axonal degeneration and cavitation, resulting in functional motor and sensory loss below the site of injury. In an attempt to overcome SCI, the regenerating neurons require a permissive environment to promote their ability to reconnect. We report a novel thiolated hyaluronic acid (HA) hydrogel scaffold that can be used to repair the injured spinal cord. More specifically, thiolated hyaluronic acid hydrogels with varying thiol concentrations were successfully synthesized. The amount of thiol groups was measured spectrophotometrically using Ellman’s test. HA gels with different crosslinking densities were synthesized and the water content of the hydrogels was determined. The thermal behavior of the HA gels were studied by DSC. The strength of the hydrogels with varying thiol group content was evaluated by a rheometer. In addition, in vitro enzymatic degradation was performed through submerge the hydrogels in 200U/ml of hyaluronidase solution and incubate at 37°C. According to the result of the present study, this novel hydrogel shows great potential to serve as a 3D cell-patterning scaffold which can be inserted into a hollow fiber channel that could be used to promote regeneration after the SCI.

This work presents an alternative approach to the production of cellulose-based biomaterials. Instead of extracting, processing and regenerating plant and or bacteria-derived cellulose into a biomaterial, my work established a decellularization protocol to remove cellular plant content from plant tissue resulting in a scaffold composed of cellulose with the evolved architecture of the plant cell wall. Tracheophyte plants, including clubmosses, horsetails, and ferns, gymnosperms and angiosperms, have evolved distinct vascular structures that support the transport of water and nutrients in xylem and phloem that form the vascular bundles (VBs)1. This thesis took it’s inspiration from the dense, linearly arranged, parallel microchannels which include (VBs) in the stalks of Asparagus officinalis possess an architecture with striking similarities to biomaterial scaffolds intended to repair damaged tissue. My work demonstrated that the plant cell wall contains many of the ideal characteristics of a medical biomaterial. The scaffold is biocompatible with mammalian cells and maintains high viability even with cell densities comparable to commercially available scaffolds. The cellulose scaffold could be biochemically functionalized or cross-linked to control the scaffolds' surface biochemistry and mechanical properties. My in vivo model demonstrated that the lignocellulose scaffold did not elicit a foreign body response. The scaffold was permissive to host cell invasion, including active host fibroblast, leading to the deposition of host collagen extracellular matrix. Importantly, active blood vessels formed within the scaffold to support the population of host cells. The scaffold retained much of its original shape and provided an inert, pro-vascular long-term environment for host cells to invade. Taken together, this led to the hypothesis that the innate plant cell wall architecture could restore the function of injured tissue, specifically that the vascular bundles could be used to promote axonal regeneration in spinal cord injuries. Rats with complete spinal cord transection were implanted with cellulose scaffolds with vascular bundles. Animals that received plant-derived scaffolds demonstrated a significant improvement in motor function. This thesis defines a novel and parallel route for exploiting naturally occurring plant microarchitectures of the underlying crystalline cellulose scaffold.