Catecholaminergic Axonal Remodeling in Motor Cortex of Mice Following Stroke
Bibliographic record
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 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".