The eﬀect of metformin on ameliorating neurological function deﬁcits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis

Frontiers in Neuroscience, 2022 · DOI: 10.3389/fnins.2022.946879 · Published: August 11, 2022

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This systematic review and meta-analysis investigates the potential of metformin, a common diabetes drug, to treat spinal cord injuries (SCI) in rats. The review analyzes multiple studies to determine if metformin can improve neurological function and reduce tissue damage after SCI. The researchers searched several databases for controlled studies that evaluated the effects of metformin on rats with SCI. They extracted data from these studies and assessed the quality of the methods and evidence. The review suggests that metformin has a protective effect on SCI in rats and demonstrates a rational mechanism of action, making it a promising candidate for future clinical trials. However, the findings should be interpreted with caution due to limitations in the animal experimental methodology and evidence quality.

Study Duration

Not specified

Participants

Laboratory rats

Evidence Level

Systematic Review and network meta-analysis

Key Findings

1
Metformin treatment was associated with increased Basso, Beattie, and Bresnahan (BBB) scores, indicating improved locomotor function in rats with SCI.
2
Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons.
3
Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin.

Research Summary

This systematic review examined the efficacy of metformin in treating spinal cord injuries (SCI) in rats. The review included 12 studies and analyzed the effects of metformin on neurological function and tissue damage. The meta-analysis indicated that metformin treatment improved locomotor recovery, tissue preservation, and the number of motor neurons in rats with SCI. The optimal dose of metformin appeared to be 50 mg/kg. The review highlights potential mechanisms of action for metformin, including activation of AMPK signaling, regulation of mitochondrial function, and alleviation of endoplasmic reticulum stress. These findings suggest that metformin is a promising candidate for future clinical trials in SCI treatment.

Practical Implications

Clinical Trials

The findings support the potential for clinical trials to evaluate metformin as a treatment for SCI in humans.

Dosage Considerations

The optimal dosage of metformin for SCI treatment appears to be around 50 mg/kg, which is below the therapeutic dose used for diabetes in humans, suggesting a need for dose titration in human trials.

Mechanism of Action

Further research into the mechanisms by which metformin affects SCI is warranted to clarify its actions and optimize its therapeutic potential.

Study Limitations

1
Substantial heterogeneity in treatment effects between the studies was presented in our review.
2
The accuracy of BBB scores largely depends on assessments of locomotion that are made subjectively.
3
The risk of missing potentially relevant articles remains because we did not have access to all possible databases and only searched for studies in English or Chinese.

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