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Regeneration and plasticity of descending motor pathways following spinal cord injury Hilton, Brett Jason
Abstract
Spinal cord injury (SCI) results in paralysis due in part to the inability of central nervous system (CNS) axons to regenerate following their transection. However, after anatomically incomplete SCI, partial spontaneous recovery can often occur. I studied the regeneration and plasticity of descending pathways involved in forelimb motor function following SCI to better understand the mechanisms underlying axon regeneration failure and spontaneous motor recovery. In Chapter 2, I developed an injury model in adult mice that results in complete axotomy of the rubrospinal tract and sustained deficits in forelimb motor function. I found that when a left dorsolateral funiculus crush injury was instigated at vertebral level C4, there were sustained deficits in left forelimb function while when the same injury was instigated at vertebral level C6, there was spontaneous recovery in left forelimb function to baseline levels. In Chapter 3, I used the injury model developed in Chapter 2 in conditional PTEN KO mice to test the hypotheses that 1) PTEN deletion promotes rubrospinal axonal regeneration following SCI and 2) Aging significantly diminishes the regenerative capacity of PTEN deleted rubrospinal neurons. I found that when PTEN was deleted within rubrospinal neurons in 4 week old mice, there was significant rostral axon growth and regeneration past the lesion site to ~1 mm relative to controls. However, when PTEN was deleted within rubrospinal neurons in 7-8 month old mice, while rostral axon growth occurred, there was no caudal regeneration. Thus, there is an age-dependent decline in regeneration of CNS neurons. In Chapter 4, I used optogenetic and chemogenetic tools to assess motor cortical plasticity in adult mice. I found that following ablation of the dorsal corticospinal tract, the motor cortex is able to re-establish output to the limbs and the minor dorsolateral corticospinal tract representing 3% of direct spinal cord transmission is able to partially mediate spontaneous recovery. Taken together, these data demonstrate an age-related decline in axon regeneration in the adult mammalian CNS and show that a minor corticospinal pathway is necessary for spontaneous recovery following SCI.
Item Metadata
Title |
Regeneration and plasticity of descending motor pathways following spinal cord injury
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2016
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Description |
Spinal cord injury (SCI) results in paralysis due in part to the inability of central nervous system
(CNS) axons to regenerate following their transection. However, after anatomically incomplete
SCI, partial spontaneous recovery can often occur. I studied the regeneration and plasticity of
descending pathways involved in forelimb motor function following SCI to better understand the
mechanisms underlying axon regeneration failure and spontaneous motor recovery.
In Chapter 2, I developed an injury model in adult mice that results in complete axotomy of the
rubrospinal tract and sustained deficits in forelimb motor function. I found that when a left
dorsolateral funiculus crush injury was instigated at vertebral level C4, there were sustained
deficits in left forelimb function while when the same injury was instigated at vertebral level C6,
there was spontaneous recovery in left forelimb function to baseline levels.
In Chapter 3, I used the injury model developed in Chapter 2 in conditional PTEN KO mice to
test the hypotheses that 1) PTEN deletion promotes rubrospinal axonal regeneration following
SCI and 2) Aging significantly diminishes the regenerative capacity of PTEN deleted rubrospinal
neurons. I found that when PTEN was deleted within rubrospinal neurons in 4 week old mice,
there was significant rostral axon growth and regeneration past the lesion site to ~1 mm relative
to controls. However, when PTEN was deleted within rubrospinal neurons in 7-8 month old
mice, while rostral axon growth occurred, there was no caudal regeneration. Thus, there is an
age-dependent decline in regeneration of CNS neurons.
In Chapter 4, I used optogenetic and chemogenetic tools to assess motor cortical plasticity in
adult mice. I found that following ablation of the dorsal corticospinal tract, the motor cortex is
able to re-establish output to the limbs and the minor dorsolateral corticospinal tract representing
3% of direct spinal cord transmission is able to partially mediate spontaneous recovery.
Taken together, these data demonstrate an age-related decline in axon regeneration in the adult
mammalian CNS and show that a minor corticospinal pathway is necessary for spontaneous
recovery following SCI.
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Genre | |
Type | |
Language |
eng
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Date Available |
2017-05-31
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0340069
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2017-02
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International