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Establishing a Murine Model of Muscle Changes in Chronic Nerve Compression
Jordan Burgess1, Jagmeet Arora2, Allen Green1
1Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Stanford University School of Medicine, Stanford, CA.
The Journal of Hand Surgery
|April 12, 2025
Summary
This study models early chronic nerve compression (CNC) in mice, revealing nerve changes and muscle atrophy markers despite preserved muscle function. This model aids research into compression neuropathies.
Area of Science:
- Neuroscience
- Muscle Physiology
- Animal Models
Background:
- Chronic nerve compression (CNC) can lead to significant muscle dysfunction.
- Previous models have limitations in fully capturing early-stage CNC effects.
- A validated model is crucial for studying interventions.
Purpose of the Study:
- To build upon a validated model of early CNC.
- To evaluate changes in muscle weight, gene expression, and function.
- To correlate nerve and muscle changes over time.
Main Methods:
- Induced CNC in mice by constricting the sciatic nerve.
- Assessed gait, muscle force, and electrodiagnostics (EDX) at 6, 8, and 12 weeks.
- Analyzed nerve and muscle tissues for weight, cross-sectional area (CSA), axon parameters, and gene expression (atrogenes, myogenesis, inflammation).
Main Results:
- Decreased nerve conduction speed and axon area, with increased g-ratio, indicating nerve damage.
- Reduced muscle weight and CSA, alongside increased atrogene expression, suggesting atrophy.
- Altered gene expression for myogenesis, fatty acid synthase, collagen, and inflammation.
- No significant differences in gait or muscle force between groups.
Conclusions:
- The developed murine model accurately reflects early CNC with nerve demyelination and axonal changes.
- Muscle atrophy markers and gene expression changes occur independently of functional deficits.
- This model provides a platform for investigating therapeutic strategies for compression neuropathies.
