The effects of cold preservation and subimmunosuppressive doses of FK506 on axonal regeneration in murine peripheral nerve isografts
Bibliographic record
Abstract
BACKGROUND: FK506 is a frequently used immunosuppressant with neuroregenerative effects. The neuroregenerative and immunosuppressive mechanisms of FK506, however, are distinct, suggesting that FK506 may stimulate nerve regeneration at lower doses than are needed to induce immunosuppression. The effects of cold preservation, a technique known to improve axonal regeneration through nerve allografts, are not well studied in nerve isografts and are also reported here. OBJECTIVES: To determine the effects of subimmunosuppressive doses of FK506 and cold preservation on nerve regeneration in isografts. METHODS: The neuroregenerative properties of immunosuppressive and subimmunosuppressive doses of FK506 were compared in a murine model receiving either fresh or cold preserved nerve isografts. Sixty female BALB/cJ mice were randomized into six groups. Animals in groups I, III and V received fresh nerve isografts. Animals in groups II, IV and VI received cold-preserved nerve isografts. Mice in groups I and II received no medical therapy, while those in groups III and IV received subimmunosuppressive doses of FK506, and those in groups V and VI received immunosuppressive doses as confirmed by mixed lymphocyte reactivity assays. Nerve regeneration was evaluated with histomorphometry and functional recovery was evaluated with walking track analysis. RESULTS: Pretreatment with cold preservation did not significantly affect neural regeneration. The potent neuroregenerative effect of immunosuppressive doses of FK506 was confirmed, and the ability of subimmunosuppressive doses of FK506 to stimulate axonal regeneration in murine nerve isografts is reported. CONCLUSIONS: Less toxic subimmunosuppressive doses of FK506 retaining some neuroregenerative properties may have a clinical role in treating extensive nerve injuries.
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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 | 0.007 |
| 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".