Differences in the Phagocytic Response of Microglia and Peripheral Macrophages after Spinal Cord Injury and Its Effects on Cell Death
Bibliographic record
Abstract
Macrophages in the injured spinal cord arise from resident microglia and infiltrating, peripherally derived monocytes. It is still not clear if macrophages derived from these two populations differ in their roles after CNS injury. The aims of this study are to investigate the phagocytic response and clearance of damaged axons and tissue debris by these distinct subsets of macrophages and assess their viability after spinal cord injury (SCI). The lysozyme M EGFP-knockin mouse tags hematogenous macrophages, but not microglia. Using a combination of immunofluorescence, flow cytometry, and neuronal tracing techniques, we show that microglia contact damaged axons early (24 h) after SCI and are the main type of macrophage to contain phagocytic material at 3 d. Thereafter, infiltrating macrophages become the predominant cell in contact with degenerating axons and contain more phagocytic material, which in contrast to microglia, persists for up to 42 d. Furthermore, after phagocytosis of myelin in vitro, bone marrow-derived macrophages are much more susceptible to apoptotic and necrotic cell death than CNS microglia, which is mirrored in vivo with apoptotic TUNEL-positive cells of infiltrating macrophage origin. This work suggests that microglia play a major role in the early response to SCI, by phagocytosing damaged and degenerating tissue, processing phagocytic material efficiently, and remaining viable. Later, macrophages of peripheral origin contribute predominantly to phagocytosis but are less efficient at processing CNS debris, and their death, in situ, may contribute to the secondary damage after CNS 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 | 0.001 | 0.001 |
| 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".