The Vasomotor Response to Dopamine Is Altered in the Rat Model of <scp>l</scp>‐dopa‐Induced Dyskinesia
Bibliographic record
Abstract
ABSTRACT Background Levodopa ( l ‐dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of l ‐dopa results in a motor complication known as levodopa‐induced dyskinesia (LID) in ~50% of patients over 5 years. Objectives We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine‐dependent vessel diameter changes. Methods Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6‐OHDA lesion) treated with 2 doses of l ‐dopa (saline, 2, and 10 mg/kg/day subcutaneous l ‐dopa treatment for 22 days) by 5‐bromo‐2'‐deoxyuridine (BrdU)‐RECA1 co‐immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2‐photon laser scanning microscopy and Dodt gradient imaging. Results We found that the 10 mg/kg l ‐dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22‐day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non‐LID animals. Dopamine‐induced vasodilatory responses were exaggerated only in rats that show LID‐like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA‐induced vasodilation is preceded by increased Ca 2+ release in the adjacent astrocytes. Conclusion This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".