A hydrogen sulfide‐releasing cyclooxygenase inhibitor markedly accelerates recovery from experimental spinal cord injury
Bibliographic record
Abstract
Spinal cord trauma causes loss of motor function that is in part due to the ensuing inflammatory response. Hydrogen sulfide (H2S) is a potent, endogenous anti-inflammatory and neuroprotective substance that has been explored for use in the design of novel nonsteroidal anti-inflammatory drugs. In the current study, we evaluated the potential beneficial effects of ATB-346 [2-(6-methoxynapthalen- 2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester], an H2S-releasing derivative of naproxen, in a murine model of spinal cord injury (SCI). SCI was induced in mice by spinal cord compression, produced through the application of vascular clips to the dura via a T5 to T8 laminectomy. ATB-346, naproxen (both at 30 μmol/kg), or vehicle was orally administered to the mice 1 and 6 h after SCI and once daily thereafter for 10 d. Motor function [Basso Mouse Scale (BMS) of locomotion] improved gradually in the mice treated with naproxen. However, those treated with ATB-346 exhibited a significantly more rapid and sustained recovery of motor function, achieving greater than double the increase in locomotion score of the naproxen group by the 10th day of treatment. ATB-346 also significantly reduced the severity of inflammation (proinflammatory cytokines, apoptosis of neural tissue, and nitrosative stress) that characterized the secondary effects of SCI. Again, the effects of ATB-346 were superior to those of naproxen for several parameters. These results showed marked beneficial effects of an H2S-releasing derivative of naproxen in an animal model of SCI, significantly enhancing recovery of motor function, possibly by reducing the secondary inflammation and tissue injury that characterizes this model. The combination of inhibition of cyclooxygenase and delivery of H2S may offer a promising alternative to existing therapies for traumatic injury.
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".