Stroke is a leading cause of death and morbidity worldwide, and leaves stroke survivors with chronic disabilities. One of the key mechanisms that the brain triggers during stroke recovery is the sprouting of new axons and the formation of new neuronal connections.
Meanwhile, studies have evidenced this phenomenon with methods using unspecific cell/axon
markers.
The dopamine (DA) system is thought to be implicated in stroke recovery. However, the
specific contribution and remodeling of this system to enhance stroke recovery, and whether D1-
class receptors play a role in this process, remain unclear. Using a mouse photothrombosis stroke
model, immunohistochemical methods, imaging analysis of axonal fiber density and branching in
the motor cortex, we demonstrated a specific dopaminergic axon remodeling in the periinfarct
region, with or without DA agonist administration. Axonal remodeling of noradrenergic fibers
was subtle. In mice subjected to saline IP injection and physical rehabilitation (running wheels),
we observed an increase of only DA fiber density in the periinfarct area as compared to the
contralateral (intact) side. However, mice treated with DHX for 7 days followed by physical
rehabilitation did not show difference between the two hemispheres. Our results suggest a
modulatory effect of DHX on axonal remodeling mainly in the contralateral side. Interestingly,
treatment of naïve mice with DHX had no effect of DA axon remodeling suggesting that D1-
mediated axonal remodeling is stroke-dependent. We also established the temporal profile of
post-stroke DA axon remodeling in the absence of DHX and physical rehabilitation. At 4 days poststroke, there was a significant decrease in DA fiber density and a significant recovery was measured after 28 days relative to the contralateral side. Altogether, our data highlight a major
remodeling of DA axons in motor cortex following stroke, and a potential role for D1-class
receptors in improving post-stroke recovery. Understanding adaptations of the DA system
following stroke will have a great impact on stroke recovery research.
Aida Said
Thesis submitted to the
Faculty of Graduate and Postdoctoral Studies
in partial fulfillment of the requirements
for the Master of Science degree in Neuroscience
Department of Cellular and Molecular Medicine
Faculty of Medicine
University of Ottawa
August 30, 2019
© Aida Said, Ottawa, Canada, 2019
Abstract
Stroke is a leading cause of death and morbidity worldwide, and leaves stroke survivors with chronic disabilities. One of the key mechanisms that the brain triggers during stroke recovery is the sprouting of new axons and the formation of new neuronal connections. Meanwhile, studies have evidenced this phenomenon with methods using unspecific cell/axon markers.
The dopamine (DA) system is thought to be implicated in stroke recovery. However, the specific contribution and remodeling of this system to enhance stroke recovery, and whether D1-class receptors play a role in this process, remain unclear. Using a mouse photothrombosis stroke model, immunohistochemical methods, imaging analysis of axonal fiber density and branching in the motor cortex, we demonstrated a specific dopaminergic axon remodeling in the periinfarct region, with or without DA agonist administration. Axonal remodeling of noradrenergic fibers was subtle. In mice subjected to saline IP injection and physical rehabilitation (running wheels), we observed an increase of only DA fiber density in the periinfarct area as compared to the contralateral (intact) side. However, mice treated with DHX for 7 days followed by physical rehabilitation did not show difference between the two hemispheres. Our results suggest a modulatory effect of DHX on axonal remodeling mainly in the contralateral side. Interestingly, treatment of naïve mice with DHX had no effect of DA axon remodeling suggesting that D1-mediated axonal remodeling is stroke-dependent. We also established the temporal profile of post-stroke DA axon remodeling in the absence of DHX and physical rehabilitation. At 4 days post-stroke, there was a significant decrease in DA fiber density and a significant recovery was measured after 28 days relative to the contralateral side. Altogether, our data highlight a major remodeling of DA axons in motor cortex following stroke, and a potential role for D1-class receptors in improving post-stroke recovery. Understanding adaptations of the DA system following stroke will have a great impact on stroke recovery research.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/40046 |
| Date | 09 January 2020 |
| Creators | Said, Aida |
| Contributors | Tiberi, Mario |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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