Abstract
Background Axonal regeneration in peripheral nerve after injury is a complicated process. Numerous cytokines, growth factors, channels, kinases, and receptors are involved, and matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis subsequent to nerve injury. In this study, the effect of KMUP-1, an activator of large-conductance Ca2+-activated potassium channel, on functional recovery, myelinated axon growth, and immunoreactivity of MMP-9 was evaluated in rats subjected to sciatic nerve crush injury. Method A total of 144 male Sprague-Dawley rats were divided into the following six groups (n = 24/group): Group 1, sham-operated; Group 2, sciatic nerve injury without treatment; Group 3, injured and vehicle-treated; Group 4, injured and treated with 1 mM KMUP-1 by topical application; Group 5, injured and treated with 10 mM KMUP-1; and Group 6, injured and treated with 50 mM KMUP-1. Functional recovery was evaluated using walking track analysis at 1, 2, 3, and 4 weeks (n = 6/group at each time point) after injury. In addition, the number of myelinated axons and MMP-9 in the nerve was also examined. Findings Animals subjected to sciatic nerve crush injury had decreased motor function, reduced number of myelinated axons, and increased MMP-9 in the nerve. Treatment with KMUP-1 concentration-dependently improved functional recovery, increased the number of myelinated axons, and decreased MMP-9. Conclusions These results suggest that KMUP-1 may be a novel agent for assisting peripheral nerve recovery after injury. The beneficial effect is probably due to known ability of the compound in activating the nitric oxide/cGMP/protein kinase G pathway.
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