An Examination of the Role of CX3CR1 in the Pathobiology of Degenerative Cervical Myelopathy: Evidence from Human and Mouse Tissue
Bibliographic record
Abstract
Background/Objectives: The molecular cascades involved in the induction and maintenance of neuroinflammation resulting from chronic compression of the cervical spinal cord in the setting of degenerative cervical myelopathy (DCM) have yet to be defined. Here, we determined the role of the fractalkine receptor, CX3CR1, during the neuroinflammatory response in a novel mouse model of DCM and demonstrated the relevance of this mechanism with human DCM tissue. Methods: Using our murine DCM model alongside the CX3CR1-knockout mice and a neutralizing antibody of CX3CR1 in wild-type mice, we examined protein, neurobehavioural and immunohistochemical readouts. The animal data were then complemented with immunohistochemical results from human post-mortem spinal cord tissue from individuals with DCM. Results: Humans and mice with DCM exhibited an up-regulation of CX3CR1 as well as markers of activated microglia/macrophages in the cervical spinal cord. Knockout and neutralization of CX3CR1 hindered microglia/macrophage activation and accumulation at the site of spinal cord compression. DCM mice exhibited decreased body speed and increased stance phase duration, which mirrors human DCM gait deficits. Strikingly, both CX3CR1 deficiency and CX3CR1 neutralization alleviated these gait deficits in DCM mice. Conclusions: Collectively, these data provide strong evidence that CX3CR1 plays a critical role in the secondary injury of neural structures in the setting of DCM. Further, targeting of CX3CR1 represents a promising therapeutic strategy to enhance neurological outcomes in DCM.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".