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Permanent link (DOI): https://doi.org/10.7939/R35H7C49X

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Promoting Neuroplasticity To Repair The Injured Spinal Cord Open Access

Descriptions

Other title
Subject/Keyword
NT-3
neurotrophins
BDNF
reticulospinal tract
spinal cord injury
rehabilitative training
single pellet reaching
corticospinal tract
plasticity
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Weishaupt, Nina
Supervisor and department
Fouad, Karim (Rehabilitation Medicine)
Examining committee member and department
Hamilton, Trevor (Psychology at MacEwan)
Dickson, Clayton (Physiology)
Mushahwar, Vivian (Physical Medicine and Rehab)
Kerr, Bradley (Pharmacology)
Sofroniew, Michael (Neurobiology at University of California)
Department
Centre for Neuroscience
Specialization

Date accepted
2013-06-10T14:30:41Z
Graduation date
2013-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
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.
Language
English
DOI
doi:10.7939/R35H7C49X
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Weishaupt N., Hurd C., Wei D.Z., Fouad K. Reticculospinal plasticity after cervical spinal cord injury in the rat involves withdrawal of projections below the injury. Exp. Neurol. 2013; in press.Weishaupt N., Vavrek R., Fouad K. Training following unilateral cervical spinal cord injury in rats affects the contralesional forelimb. Neurosci. Lett. 2013; 539:77-81.Weishaupt N., Li S., Di Pardo A., Sipione S., Fouad K. Synergistic effects of BDNF and rehabilitative training on recovery after cervical spinal cord injury. Behav. Brain Res. 2013; 239:31-42.

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