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A treatment for SCI: From regeneration and plasticity to rehabilitative training Open Access


Other title
reticulospinal tract
skin-derived precursor Schwann cells
propriospinal interneurons
Spinal cord injury
hyaluronan methylcellulose hydrogel
Type of item
Degree grantor
University of Alberta
Author or creator
May, Zacnicte
Supervisor and department
Fouad, Karim (Faculty of Rehabilitation Medicine)
Examining committee member and department
Bennett, David (Faculty of Rehabilitation Medicine)
Kerr, Bradley (Pharmacology)
Centre for Neuroscience

Date accepted
Graduation date
2017-11:Fall 2017
Doctor of Philosophy
Degree level
Spinal cord injury (SCI) is an extremely debilitating condition, leading to sensory and motor dysfunction below the level of the injury. Presently, there are few effective treatments for SCI. This is in part due to the immense complexity of SCI pathophysiology. Thus, combined research approaches are required, but translating individual approaches, let alone combined ones poses a great challenge. In my thesis, I study different aspects of SCI that should be considered for combined treatments, including cell grafting to promote regeneration of injured spinal axons (Chapters 1 and 2), plasticity of injured and spared systems (Chapter 3), and rehabilitation treatment strategies (Chapter 4 and Appendices). Chapters 1 and 2 address cell grafting and an associated challenge, i.e. tumour formation. This is a risk especially when grafting stem cell and stem cell-derived cells and can possibly be eliminated given modifications in cell culture protocols. Meticulous research is urgently needed to define the exact parameters that will reduce this risk. Chapter 3 shows that descending reticulospinal axons form new connections with propriospinal interneurons, adding to the multiplicity of known recovery mechanisms post-SCI. The multiplicity of known recovery mechanisms provides opportunity for numerous possible targets to promote recovery. Chapter 4 demonstrated that pre-injury task-specific training impacts post-SCI recovery, advising that pre-injury variables deserve careful consideration in experimental design, clinical application, and reusing the same animals in multiple scientific studies. Understanding these different aspects of SCI will inform future combinatory treatments. For example, a combinatory treatment can be envisioned where cells are injected in the cavity commonly formed in the spinal cord after injury, creating a bridge for growing axons. Then, to promote neuronal rewiring, soma of descending systems could be infused with growth factors and drawn to appropriate synaptic targets with chemoattractants. Lastly, these plastic mechanisms could be consolidated through rehabilitative training.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
May, Z., Fouad, K., Shum-Siu, A., & Magnuson, D. S. K. (2015). Challenges of animal models in SCI research: Effects of pre-injury task-specific training in adult rats before lesion. Behavioural Brain Research, 291, 26–35.
, K. K., May, Z., Hurd, C., Boychuk, C. E., Kowalczewski, J., Bennett, D. J., ... Fouad, K. (2015). Improved single pellet grasping using automated ad libitum full-time training robot. Behavioural Brain Research, 281, 137–148.
, K. K., May, Z., Torres-Espín, A., Forero, J., Bennett, D. J., & Fouad, K. (2016). Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot. Behavioural Brain Research, 299, 59–71.

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