Late motor decline after accomplished remyelination: Impact for progressive multiple sclerosis
Bibliographic record
Abstract
OBJECTIVE: To investigate the impact of single or repeated episodes of reversible demyelination on long-term locomotor performance and neuroaxonal integrity, and to analyze the myelin proteome after remyelination and during aging. METHODS: Long-term locomotor performance of previously cuprizone-treated animals was monitored using the motor skill sequence (MOSS). Quantitative analysis of myelin proteome and histopathological analysis of neuronal/axonal integrity was performed after successful remyelination. Histopathological findings observed in experimental chronic remyelinated lesions were verified in chronic remyelinated lesions from multiple sclerosis (MS) patients. RESULTS: Following cessation of cuprizone treatment, animals showed an initial recovery of locomotor performance. However, long after remyelination was completed (approximately 6 months after the last demyelinating episode), locomotor performance again declined in remyelinated animals as compared to age-matched controls. This functional decline was accompanied by brain atrophy and callosal axonal loss. Furthermore, the number of acutely damaged amyloid precursor protein-positive (APP+) axons was still significantly elevated in long-term remyelinated animals as compared to age-matched controls. Confocal analysis revealed that a substantial proportion of these APP+ spheroids were ensheathed by myelin, a finding that was confirmed in the chronic remyelinated lesions of MS patients. Moreover, quantitative analysis of myelin proteome revealed that remyelinated myelin displays alterations in composition that are in some aspects similar to the myelin of older animals. INTERPRETATION: We propose that even after completed remyelination, axonal degeneration continues to progress at a low level, accumulating over time, and that once a threshold is passed axonal degeneration can become functionally apparent in the long-term. The presented model thus mimics some of the aspects of axonal degeneration in chronic progressive MS.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".