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Metformin Improves Functional Outcomes, Activates Neural Precursor Cells, and Modulates Microglia in a Sex-Dependent
Emily A B Gilbert1,2,3, Jessica Livingston1,2,3, Emilio Garcia-Flores1,2,3,4
1Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Canada.
Stem Cells Translational Medicine
|May 20, 2023
Summary
Metformin enhances functional recovery after spinal cord injury (SCI) by activating neural stem and progenitor cells (NSPCs) and oligodendrocyte precursor cells (OPCs). Acute administration shows promising therapeutic potential for SCI repair in both sexes.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pharmacology
Background:
- Spinal cord injury (SCI) leads to severe patient outcomes with limited treatment options.
- Endogenous neural stem and progenitor cells (NSPCs) and oligodendrocyte precursor cells (OPCs) activate after SCI but are insufficient for functional recovery.
- Metformin, an FDA-approved drug, promotes brain repair and NSPC activation post-injury.
Purpose of the Study:
- To investigate the efficacy of metformin in promoting functional recovery and neural repair following SCI in both male and female subjects.
- To determine the effects of acute versus delayed metformin administration on SCI outcomes.
- To explore sex-dependent effects of metformin on cellular repair mechanisms in the injured spinal cord.
Main Methods:
- Administration of metformin (acute or delayed) to subjects with SCI.
- Assessment of functional outcomes post-SCI.
- Analysis of NSPC and OPC activation and oligodendrogenesis.
- Evaluation of sex-specific cellular responses, including microglia activation.
Main Results:
- Acute metformin administration significantly improved functional outcomes in both sexes following SCI.
- Functional recovery was associated with increased OPC activation and oligodendrogenesis.
- Metformin exhibited sex-dependent effects: enhanced NSPC activation in females and reduced microglia activation in males.
Conclusions:
- Acute metformin administration represents a viable therapeutic strategy for improving functional outcomes after SCI.
- Metformin demonstrates pleiotropic effects in the spinal cord, influencing distinct cellular repair pathways.
- The findings highlight the potential of metformin in SCI treatment, with considerations for sex-specific responses.
