We aimed to explore previously reported discrepancies in success with leupeptin by comparing outcomes of two types of injury: transection and crush. Male rats were randomized into vehicle and leupeptin treatment groups (n = 6/transection group; n = 10/crush group). Leupeptin (12 mg/kg) was administered via intramuscular injection into the gastrocnemius muscle twice a week for the duration of the study. Rats were monitored on a weekly basis for electromyographic function and gait for 8 weeks. A total of 83.3% of the rats that were treated with leupeptin began to recover electromyographic activity 1 week after transection, versus 0% that were treated with leupeptin after crush (P < 0.0001). Rats that were treated with leupeptin also had less functional debilitation, as indicated by a greater sciatic functional index at five of the eight time-points after transection versus one of eight after crush (P ≤ 0.05). Leupeptin aids in the rate of recovery after transection and repair but not crush injuries. These findings suggest there may be differences in pathology and recovery associated with these two types of peripheral nerve injury.
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