Metformin Activates Neural Stem and Progenitor Cells in the Spinal Cord and Improves Functional Outcomes Following Injury
Bibliographic record
Abstract
Across mammals, spinal cord injuries (SCI) result in devastating functional deficits with minimal treatment options. Neural stem and progenitor cells (NSPCs) exist within the spinal cord and are located in the periventricular region lining the central canal. Although normally relatively quiescent and non‐neurogenic, these NSPCs are activated in response to injury, however their response is not sufficient to support functional recovery. Enhancing the response of resident NSPCs is an innovative approach to improve structural and functional outcomes following SCI. The FDA‐approved drug metformin (MET) has demonstrated efficacy in promoting neural repair in the injured brain where it expands the size of the NSPC pool and promotes both oligogenesis and neurogenesis from NSPCs. Here, we seek to determine whether MET can influence NSPCs within the spinal cord prior to and following SCI. Using the in vitro colony‐forming assay (neurosphere assay) we examined the size of the neural stem cell (NSC) pool in the spinal cord following 7 days of in vivo MET treatment. Females, but not males, demonstrated a three‐fold increase in the size of the NSC pool in response to MET treatment. Conversely, the differentiation profile of male and female‐derived NSPCs was not sex dependent in the presence of MET. Our results show that MET exposure led to an increase in oligogenesis across both males and females, with no change in neurogenesis. Next, we evaluated whether MET administration would improve functional outcomes following SCI using a dorsal column lesion in the thoracic spinal cord. MET was delivered to animals immediately post‐SCI and treatment resulted in a significantly reduced impairment at 7 days post‐injury (DPI) on a skilled walking task, compared to vehicle‐treated SCI mice. Strikingly, MET‐treated mice recovered to baseline by 14 DPI. Our data reveals that MET has differential effects on spinal cord NSPCs across males and females and that MET administration reduces the severity of SCI and results in improves functional outcomes post‐injury. Taken together, our results support MET as a viable therapeutic strategy for enhancing neural repair and improving recovery following SCI. Support or Funding Information American Association of Anatomists Ontario Institute for Regeneration Medicine Krembil Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.002 | 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".