Assisted peripheral nerve recovery by KMUP-1, an activator of large-conductance Ca2+-activated potassium channel, in a rat model of sciatic nerve crush injury

作者：Chung Chia Li; Tsai Hung Pei; Lee Kung Shing; Chen Kuang I; Wu Shu Chuan; Kuo Yen Hsin; Winardi William; Chen Ing Chun; Kwan Aij Lie^*

来源：Acta Neurochirurgica, 2012, 154(10): 1773-1779.

DOI：10.1007/s00701-012-1433-y

• KMUP-1
• BKCa activator
• Sciatic nerve crush injury
• Sciatic function index
• MMP-9

Axonal regeneration in peripheral nerves 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. %26lt;br%26gt;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; 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. %26lt;br%26gt;Animals subjected to sciatic nerve crush injury had decreased motor function, a 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. %26lt;br%26gt;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.

• 出版日期2012-10
• 单位河北医科大学