Abstract

PURPOSE: Peripheral nerve injury (PNI) outcomes remain largely unchanged for decades. Scar formation following PNI poses a physical barrier to axonal regeneration. Murphy Roths Large (MRL/MpJ) mice have demonstrated minimal scar formation in wound and tendon healing. This study seeks to evaluate whether this attribute improves peripheral nerve regeneration. METHODS: Six-week old male mice were divided into two groups: 1) Nerve Repair (NR, n=60) and 2) Nerve Graft (NG, n=60). The C57BL/6J was compared to the MRL/MpJ strain. The right sciatic nerve was either divided and microsurgically repaired (NR) or, had a 5mm segment excised, reversed and re-interposed (NG). The Sciatic Functional Index (SFI) was used to record functional recovery at post-operative weeks (POW) 1, 3, 6, 9, and 12. Sciatic nerves were harvested and processed to calculate axon counts and the ‘g’ ratio for each end-point. RESULTS: The MRL/MpJ strain demonstrated significantly superior SFI scores at POW 1, 3 (NR group) and at POW 6 (NG group). Axon counts were significantly higher in the C57BL/6J strain at POW 3 and 6 (NR group), and at POW 6, 9, and 12 (NG group). The MRL/MpJ strain demonstrated a significantly better axonal myelination at POW 3, 6, 9, and 12 (DR group) and at POW 6 and 12 (NG group). CONCLUSION: This study demonstrates superior axonal regeneration in the MRL/MpJ strain. The results support the notion that the quality is more important than the quantity of regenerating axons. Future work implementing a mechanistic that targets nerve scarring is warranted.

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