Promoting Neuroplasticity To Repair The Injured Spinal Cord

• Author / Creator

  Weishaupt, Nina

• This thesis explores strategies to promote neuronal plasticity in a rat model of cervical spinal cord injury (SCI) in an effort to achieve improved recovery of skilled forelimb use. I focused on investigating how motor pathways disrupted by an SCI may connect to spared, lesion-bridging relay pathways to re-establish communication with target regions below the injury level. In chapter 2, I attempted to promote a detour for the cervically injured corticospinal tract (CST) via spared reticulospinal tract (RtST) axons with a combined treatment including the neurotrophins BDNF, NT-3 and rehabilitative training. Although anatomical evidence for the desired rewiring was not obtained, I found a synergistic effect of BDNF treatment and training on recovery of skilled forelimb reaching. No effect of NT-3 administered rostral to the SCI was evident. The experiment in chapter 3 was designed to answer the question whether NT-3-induced CST collateral growth rostral to an SCI can be facilitated by systemic immune activation. Results indicate that NT-3 expression can promote collateral growth from the injured CST, irrespective of immune activation. Since results from chapter 2 did not shed light on the previously suggested role of the RtST in recovery of hand/paw function after cervical SCI, I next examined whether the mostly spared RtST responds to SCI with changes in its anatomical projection pattern. While collateral projections were unchanged rostral to the SCI, I observed a marked withdrawal of collaterals from grey matter regions directly caudal to the SCI. Results from chapter 2 combined with previous reports indicate that task-specific training does often not translate into untrained tasks and may even result in undesired side effects. To elucidate the functional relationship between trained tasks further, I next investigated how training the primarily affected forelimb (PAF) and/or the less affected forelimb (LAF) after unilateral cervical SCI influences performance outcomes for each limb. Results point towards training tasks competitively recruiting available neuronal “hardware”. This work identifies promising leads for promoting plasticity of important motor tracts after SCI, and also points out targets for optimization of strategies employed. These new insights contribute to the exploration of urgently needed repair strategies for SCI.

• Subjects / Keywords

  • Reticulospinal tract
  • NT-3
  • Neurotrophins
  • Plasticity
  • Spinal cord injury
  • Corticospinal tract
  • Rehabilitative training
  • Single pellet reaching
  • BDNF

• Graduation date

  Fall 2013

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R35H7C49X

• 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.