Motor cortex electrical stimulation in rats with a cervical spinal cord injury to promote axonal outgrowth

  • Author / Creator
    Jack, Andrew S
  • Objective Many treatment regimens for improving recovery after spinal cord injury (SCI) in humans have been trialed with limited success. Electrical stimulation (ES) to promote spinal cord repair has been more recently examined as a SCI treatment modality in animals, though remains under investigated. Here, we examined the role of motor cortex ES on axonal re-growth, plasticity, and functional recovery in a SCI rat model. Materials and Methods A dorsal lateral quadrant transection at C4 in 48 rats was performed after Montoya grasping stairwell training. Rats were divided into 4 groups: 1) ES333 (n=14; 333Hz, biphasic pulse, 0.2ms duration every 500ms with 30 pulses per train); 2) ES20 (n=14; 20Hz, biphasic pulse, 0.2ms duration every 1s with 60 pulses per train); 3) SCI only (n=10); 4) sham (n=10; electrode insertion without ES). ES of the forelimb motor cortex corresponding to the injured corticospinal tract (CST) for 30 minutes at the time of SCI surgery was performed. Post-injury grasping scores were recorded weekly for 4 weeks. Axonal collateralization and dieback at multiple points were quantified using bright-field microscopy after CST labeling. Behavioural outcomes and histological outcomes were found to be no different between SCI only and sham rats, and as such the two groups were combined into one ‘control’ group. Significance level for between-group comparisons (ANOVA or Kruskal-Wallis for non-parametric data with subsequent post-hoc testing) was set at p<0.05. Results Post-SCI grasping success and furthest well reached scores were significantly lower than baseline values (p<0.01, Tukey test) for all groups. ES20 animals had significantly lower grasping scores and lower furthest well reached scores post-SCI than controls (p=0.03 for both, Tukey test). Significantly more axonal collaterals (i.e., axonal sprouts rostral to the lesion) were found in the ES333 animals compared to control animals (p<0.01, Mann-Whitney test). No difference was found with respect to the number of collaterals between the two ES groups (p=0.10, Mann-Whitney test), nor between the ES20 and control groups (p-value 0.16, Mann-Whitney test). Beginning at 100μm rostral to the injury, ES20 rats had significantly more axonal dieback (axon count rostral to SCI) than the ES333 rats (p=0.03, Tukey test). At both 50μm rostral to injury and at the injury site, ES20 rats had significantly more axonal dieback than controls and ES333 rats (50μm mark: p=0.02 and 0.02, respectively, Tukey test; lesion site: p=0.01 and 0.02, respectively, Tukey test). Conclusion We have demonstrated that motor cortex ES of the injured CST results in greater axonal collateralization. The extent of axonal retraction rostral to SCI and behavioural outcomes also seem to vary with different ES parameters. Collectively, our data suggests that ES represents a potentially promising SCI therapy to promote axonal outgrowth, but further investigation is required.

  • Subjects / Keywords
  • Graduation date
    2016-06:Fall 2016
  • Type of Item
  • Degree
    Master of Science
  • 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.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Centre for Neuroscience
  • Supervisor / co-supervisor and their department(s)
    • Fouad, Karim (Faculty of Rehabilitation Medicine)
  • Examining committee members and their departments
    • Smith, Peter (Faculty of Medicine and Dentistry, Department of Pharmacology)
    • Nataraj, Andrew (Faculty of Medicine and Dentistry, Department of Surgery)
    • Colbourne, Fred (Department of Psychology)
    • Kerr, Brad (Faculty of Medicine and Dentisty, Department of Pharmacology)
    • Gorassini, Monica (Faculty of Medicine and Dentistry)