6. Surfen, a proteoglycan antagonist, reduces lysolecithin-induced demyelination with related effects on macrophage function
Bibliographic record
Abstract
Proteoglycans are components of the extracellular matrix and have roles in brain development and responses to injury. Connective tissue components are known to be major inhibitors of remyelination in mouse models of demyelination and are found at the border of active demyelinating lesions in Multiple Sclerosis. Surfen (bis 2-methyl, 4- amino, 6-quinolyl amide) is a small molecule antagonist previously shown to bind preferentially to heparan sulfate and related proteoglycans. We have previously reported that surfen reduces T cell proliferation in vivo and in vitro. Here we report the effects of surfen on an in vivo model of demyelination and its effects on macrophage function in vitro. Demyelination was induced by injecting the detergent lysolecithin into the spinal cord dorsal columns of adult C57Bl/6 mice. Relative to vehicle treated mice, co-injection of surfen (100 μM) with lysolecithin reduced total lesion area seven days post-injection. Because macrophages dominate these lesions and influence remyelination, murine bone marrow derived macrophages were assessed using assays of chemotaxis and phagocytosis. Macrophages chemotaxis was increased in response to surfen (10 μM) relative to vehicle by approximately 15% (p<0.05). Phagocytosis of E. coli was not affected by surfen. These effects of surfen on experimental demyelination and macrophage function suggest that proteoglycan binding may promote aspects of myelin repair relevant to Multiple Sclerosis.
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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 | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".