Assisted peripheral nerve recovery by KMUP-1, an activator of large-conductance Ca(2+)-activated potassium channel, in a rat model of sciatic nerve crush injury

• Published in: Acta neurochirurgica Vol. 154; no. 10; pp. 1773 - 1779
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Austria 01.10.2012
• Subjects: Animals; Axons - drug effects; Axons - pathology; Disease Models, Animal; Male; Matrix Metalloproteinase 9 - metabolism; Nerve Crush - methods; Nerve Regeneration - drug effects; Peripheral Nerve Injuries - drug therapy; Piperidines - therapeutic use; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Sciatic Nerve - drug effects; Sciatic Nerve - injuries; Xanthines - therapeutic use
• ISSN: 0942-0940
• DOI: 10.1007/s00701-012-1433-y

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 Ca(2+)-activated potassium channel, on functional recovery, myelinated axon growth, and immunoreactivity of MMP-9 was evaluated in rats subjected to sciatic nerve crush injury. 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. 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. 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.