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

  • Author / Creator
    May, Zacnicte
  • 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.

  • Subjects / Keywords
  • Graduation date
    Fall 2017
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. 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.