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Validating a Murine Model of Muscle Atrophy in Chronic Nerve Compression
Jordan J Burgess, BA1,2; Evan Jarman, BS1; Kate Hayashigatani, BS1; Zhen Wang, MD3; James Chang, MD4,5; Paige M Fox, MD, PhD1,3
1Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; 2Stanford University School of Medicine, Stanford, CA; 3Stanford University, Palo Alto, CA; 4Plastic and Reconstructive Surgery, Stanford University, Palo Alto, CA; 5Plastic and Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA

Introduction - Chronic compression neuropathies are characterized by progressive demyelination, impaired nerve conduction velocity, and muscle atrophy. Previous studies have established a model of chronic nerve compression (CNC) in mice, however these studies did not investigate changes to the muscle. We aim to establish and validate a mouse model of muscle atrophy in CNC and to correlate changes in muscle weight and fiber size with changes in nerve conduction speed (NCS), compound motor action potential (CMAP) amplitude, myelination, and axon integrity.
Materials & Methods CNC was induced by placing a silastic tube around the sciatic nerve with the contralateral limb as a control. At 6, 8 and 12 weeks, NCS and CMAP amplitude were assessed, and the gastrocnemius (GN), tibialis anterior (TA), and sciatic nerve were harvested bilaterally. Muscle weight, fiber size using wheat germ agglutin staining, axon integrity using neurofilament H (NFH) staining, and myelination using myelin protein zero (MPZ) staining were measured. Data are expressed as fold change compared to control. Differences were considered significant at p<0.05.
Results GN and TA muscle weight were significantly reduced at 6, 8, and 12 weeks compression with maximum fold-change observed at 8 weeks with 0.82 0.08 fold change for GN, and 0.80 0.07 for TA.Muscle fiber cross-sectional area was reduced at all time-points with maximum fold change observed at 12 weeks. Differences were significant across time-points for both outcomes.
NCS and CMAP amplitude were reduced at all time-points. Maximum decline in NCS was observed at 8 weeks with 0.71 0.07 fold change. Maximum decline in CMAP amplitude was observed at 12 weeks with 0.57 0.16 fold change. Lastly, NFH and MPZ fluorescence intensity were reduced greater than 50% at 8 and 12 weeks compression. Data are summarized in Table 1.
Conclusions The murine model of CNC demonstrates reduced muscle weight and decreased muscle fiber cross-sectional area. Muscle atrophy correlates with slower NCS, reduced axon integrity, and demyelination. These findings establish a mouse model of muscle atrophy in CNC that will allow us to determine the pathophysiology muscle atrophy and develop new therapies for compression neuropathies.


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