Current treatments for spinal cord injury (SCI) are extremely limited due to the fact that the central nervous system lacks the intrinsic ability to regenerate, and constitutes a poor environment for regenerative axon growth. Nerve tissue engineering is an emerging field with the aim of repairing or creating new nerve tissues to promote functional recovery by using artificial tissue repair scaffolds. The design of a stable and consistent animal model of SCI is essential to study the effectiveness of scaffolds in promoting nervous system repair. In this study, a partial transection animal model was created with a three dimensional lesion at T8-T9 that disrupts axonal pathways unilaterally in the dorsal columns of the rat spinal cord. Alginate hydrogel scaffolds incorporating living Schwann cells were fabricated to evaluate the abilities of those scaffolds to foster axonal regeneration. The surgical technique was improved to provide better outcomes related to bleeding during surgery, weight control, neurological function and surgery duration. The survival rate of animals during the surgical procedure and post-surgery period was ultimately increased to 100%. Histology and immunohistochemistry results indicated that implanted alginate scaffolds may induce larger cavities and extenuate harmful inflammation responses, but that effect was ameliorated by inclusion of Schwann cells in the scaffold. However, neither plain alginate scaffolds nor scaffolds containing living Schwann cells were able to improve regeneration of identified axon tracts in the spinal dorsal columns. This research also employed a synchrotron based x-ray phase contrast imaging technique coupled with computed-tomography to visualize the low optical density structural features of scaffolds and spinal cord tissues in formaldehyde fixed specimens. The imaging results suggest that this is a promising method for analyzing the structure of tissue repair scaffolds within the spinal cord. This degree of structural characterization, potentially applicable to living tissue, is not afforded by other conventional image analysis techniques.

published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Master of Medical Sciences

Spinal cord injury is a devastating source of suffering in the spectrum of human pathophysiology; advancement for clinical therapy in this area has been stagnant in comparison to modern medical development. Current treatments are palliative, and functional recovery is minimal. During the first two weeks after injury, dense glial scar forms that is impenetrable by regenerating axons. Intervention is imperative to minimize scar formation and provide a supportive environment for axonal regeneration. Oligodendrocytes are critical to maintain the health of growing axons during development and after injury. Obtaining these cells through differentiation of neural progenitor cells (NPCs) is a viable option, but current clinical trials involving stem cells are plagued by poor cell survival and undirected differentiation. Research indicates that local extracellular matrix (ECM) is vital to progenitor differentiation and tissue regeneration. During development, spinal cord ECM is comprised of high concentrations of laminin and hyaluronic acid (HA), which provide essential cues to direct NPC migration and differentiation. The purpose of this research is to create a biomaterial optimized to direct NPC differentiation to oligodendrocytes. Natural biomaterials were optimized from distinct combinations of collagen I, HA, and laminin I to model the native ECM signals found during oligodendrocyte maturation. Four material combinations (collagen, collagen-HA-laminin, collagen-HA, and collagen-laminin) were fabricated into injectable hydrogels to mimic the range of compressive and shear mechanical properties present in neonatal central nervous system (CNS) tissue. Differentiation was assessed by culturing rodent fetal NPCs in these materials without specific soluble factors to direct cellular behavior. The three-component hydrogel performed optimally and achieved a 66% oligodendrocyte differentiation rate compared to approximately 15% in the collagen alone hydrogel. An in vivo study was then conducted using a rat contusion model of spinal cord injury with intervention using the injectable, three-component hydrogel seeded with rat NPCs. Functional recovery was assessed using six behavioral tests. Significant recovery was observed using two behavioral tests six weeks post-treatment. Lesion size was measured and correlated well with behavioral outcomes. The data obtained in this research indicate that a multi-component hydrogel mimicking native, developmental CNS tissue may address problems associated with current clinical practice. / text

Abstract Purpose: To characterize physical activity of people using manual wheelchairs with spinal cord injury in Manitoba. Methods: An observational study of manual wheelchairs users with spinal cord injury. Participants completed surveys related to self-efficacy for exercise, physical activity participation, and shoulder pain. Accelerometers were worn for 7 days on the wrist and trunk (GT3X, 100 Hz, 5 s epochs) and completed an activity log concurrently. Individual specific thresholds were determined for moderate intensity during a pace graded wheeling trial. Physical activity and sedentary time were characterized using various derived variables. Results: Twenty five participants (12 tetra:13 para, 21M:4F) demonstrated excellent accelerometer adherence achieving an average of 6.2 days worn for over 13 hours per day. A total of 74.6 min (all activity) and 115 min (contiguous bouts of activity) were achieved over time worn (6.2 days), corresponding to 11.8 and 18.5 min/day respectively. The participants substantially exceeded the published SCI guidelines (40 min/week, P<0.01) but were under the able bodied threshold of 150 min/week (P<0.01). No relationships were observed between surveys and objectively measured PA. Characterization of PA bouts revealed few participants (n=7) exhibiting single bout durations greater than 10 minutes, with an average contiguous bout duration of 30 s. A new functional classification scheme revealed positive correlations to PA variables and wheeling performance. Sedentary times ranged from 6.25 to 8.4 hours per day depending upon accelerometer placement. Conclusion: Arm based accelerometry can be used to determine PA and sedentary characteristics of manual wheelchair users with individual specific moderate intensity thresholds. Participants exceeded the SCI specific activity guidelines in terms of time per week, and failed to reach bout durations of 20 min. This study supports the use of able-bodied PA guidelines as a target. A new functional classification scheme was derived based upon wheeling dependent muscle innervation that had enhanced prediction of PA relative to standard anatomical classification / October 2015

Individuals with spinal cord injury (SCI) demonstrate reduced limb blood flow and muscle spasticity. It is plausible that the accumulation of metabolites, resulting from reduced perfusion, could exacerbate spasticity via activation of fusimotor neurons by Group III and IV afferents. PURPOSE: To determine the association between peripheral blood flow and muscle spasticity in persons with SCI. METHODS: A total of 16 individuals with SCI were classified into high (N=6), low (N=5), and no (N=5) spasticity groups according to their spasticity levels indicated by the modified Ashworth scale scores. Blood flow was measured in femoral and brachial arteries using duplex Doppler ultrasound and was normalized to limb lean mass obtained with dual energy X-ray absorptiometry. RESULTS: There were no significant group differences in age (30.5±4.15, 38.48±4.61, 32.6±4.89 years), time post SCI (8.5±4.2, 12.6±4.74, 6.8±1.66 years), American SCI Association motor scores (39.2±7.78, 59±12.34, 53.4±1.08), or sensory scores (96±22.1, 144.4±13.97, 130±13.8). Femoral artery blood flow, adjusted for limb lean mass, was significantly different (p=0.002) across the three leg spasticity groups (high 76.03±6.44, low 95.12±15.49, no 142.53±10.86 ml/min/kg).Total leg muscle spasticity scores were significantly and negatively correlated with femoral artery blood flow (r=-0.60, p=0.014). There was no significant difference in brachial artery blood flow between the three groups, indicating that the reduction in blood flow was confined to injured limbs and not due to systemic cardiovascular disorder. CONCLUSION: Among SCI patients, whole-leg blood flow is progressively lower in individuals with greater spasticity scores. These results suggest that a reduction in lower limb perfusion, among other factors, plays a significant role in the pathogenesis leading to muscle spasticity after SCI. / text

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

Bipeds and quadrupeds are inherently unstable and their bodies sway during quiet stance and require complex patterns of muscle activation to produce direction-specific forces to control the body’s center of mass. The relative strength of length and force feedback within and across muscles collectively regulates the mechanical properties of the limb as a whole during standing and locomotion (Bonasera and Nichols 1994; Ross and Nichols 2009). Loss of posture control following spinal cord injury (SCI) is a major clinical challenge. While much is known about intermuscular force feedback during crossed extension reflex (XER) and locomotion in decerebrate cats, these have not been well characterized in animals with spinal cord injury. In this study, we mapped the distribution of heterogenic force feedback in hindlimb ankle extensor muscles using muscle stretch (natural stimulation) in intercollicular, non-locomoting, decerebrate cats with chronic lateral spinal hemisection (LSH). We also, determined the time of onset of redistribution of heterogenic force feedback following LSH by collecting force feedback data from cats with acute sci. In addition we revisited heterogenic force feedback between ankle extensors in decerebrate non-locomoting cats during mid-stance to ascertain whether these cats with intact spinal cord depict a certain pattern of force feedback. The goal was to ascertain whether the patterns and strength of feedback was different between the two states (cats with intact spinal cord and cats with SCI). We found that heterogenic feedback pathways remained inhibitory in non-locomoting decerebrate cats in two states. The latencies of inhibition also corresponded to those observed for force feedback from Golgi tendon organs. We observed variable patterns of force feedback between ankle extensors in decerebrate/control cats. On the other hand we observed consistent results in cats with chronic LSH exhibiting very strong distal to proximal pattern of inhibition from 2 weeks to 20 weeks following chronic LSH. The same results were obtained in acute LSH cats suggest that the change in neuromuscular system appears immediately after SCI and persists even after the animal start walking following SCI. The observed altered pattern of force feedback after spinal cord injury suggests either presence of a pattern intrinsic to the spinal cord or a unique pattern exhibited by the damaged spinal cord. The results are important clinically because even with vigorous rehabilitation attempts patients do not regain posture control after SCI even though they regain ability to walk. Therefore, to effectively administer treatment and therapy for patients with compromised posture control, a complete understanding of the circuitry is required.

No description available.

The vocal folds are important for protection of the airway during swallowing, the regulation of breathing and for voice production. Unilateral vocal fold paralysis (UVP) is caused by damage to the recurrent laryngeal nerve (RLN). Although surgery is most often linked to onset of UVP, the cause remains unknown in 12-42% of those with this disorder [1, 2]. At the level of the aortic arch the RLN branches from the vagus nerve and courses around the arch to ascend back toward the larynx. I hypothesize that an aneurysm of the aorta or alternatively changes in aortic arch compliance could impose increased stress and strain on the RLN where it is adjacent to the aorta resulting in impaired nerve function. The purpose of this research is to develop a computational model based on the biomechanical properties of the left RLN. This model is important for formulating predictions of the typical ranges of stress and strain responses of RLN tissue to forces imposed by surrounding structures (aortic arch). These predictions may be important for future investigations using an animal model to determine the amount of stretch necessary to cause onset of UVP. The first aim of this work was to identify differences in the biomechanical properties in the RLN of piglets between its location within the neck and the portion of the left RLN within the thorax, including the aortic arch region. The distal right RLN segment showed higher maximum tangential modulus (MTM) than the left. With the left nerve the proximal segment (aortic arch region) exhibited higher values of MTM and the stiffness parameter β than the distal segment. This increased stiffness of the proximal region may be in response to the pulsatile forces near the region of the aortic arch. The second aim of this work was to identify difference in the biomechanical properties in adolescent and piglet RLN specimens, between age and between the proximal and distal segments. Additionally the collagen structure of the RLN was imaged with two-photon microscopy to compare the microstructure with the biomechanical response of the RLN tissue. The tangential modulus (TM) and full width half maximum of the collagen fiber distribution (FWHM) was larger in the proximal segments than the distal segments. The strain energy and stiffness parameter α were larger in the piglet than the adolescent pigs while the stiffness parameter β was larger in the adolescent pigs. The purpose of the third aim was to use the material constants from the second aim to create a parametric computational model of the left RLN and the aortic arch. Results indicated that the parameters with the greatest sensitivity to left RLN maximum principal stress and strain are the material properties of the aortic arch. The maximum value of strain found in the RLN region of interest was 16.1%, which may indicate that some combination of aortic arch and RLN properties can elicit damage in the RLN.