GR.6 Harnessing the endogenous regenerative potential of the injured spinal cord
Bibliographic record
Abstract
Background: The adult spinal cord contains a population of ependymal-derived neural stem/progenitor cells (epNSPCs) with the potential to enhance endogenous regeneration. However, little is known about the mechanisms that regulate the activation of these cells after injury. Recently, we discovered that glutamate excitotoxicity, a hallmark in the pathophysiology of acute SCI, promotes epNSPC proliferation/survival. Here, we characterize the downstream signaling pathways involved in this response and target this mechanism in vivo to enhance the endogenous regenerative capacity of these cells. Methods: epNSPCs were isolated from the central canal region of the adult spinal cord. In vitro pathway analysis was conducted using immunohistochemistry, RNAseq and Western Blot. In vivo, rats underwent SCI and at 1-week post-injury were randomized to receive CX546 (positive AMPAR modulator), or vehicle-control. Animals underwent behavioural testing and spinal cords were extracted for analysis. Results: Glutamate excitotoxicity leads to calcium influx in epNSPCs via AMPARs and together with Notch signaling drives proliferation and astrocytic differentiation. Positive modulation of AMPARs subacutely after SCI enhances epNSPC proliferation, astrogliogenesis, neurotrophin production, neuronal survival and functional recovery. Conclusions: We uncover an important mechanism by which AMPARs regulate the growth/phenotype of epNSPCs which can be targeted therapeutically to harness the regenerative potential of the injured spinal cord.
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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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".