title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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.
authors: Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chia-Li
authors: CL
authors: Chung
authors: Hung-Pei
authors: HP
authors: Tsai
authors: Kung-Shing
authors: KS
authors: Lee
authors: Kuang-I
authors: KI
authors: Chen
authors: Shu-Chuan
authors: SC
authors: Wu
authors: Yen-Hsin
authors: YH
authors: Kuo
authors: William
authors: W
authors: Winardi
authors: Ing-Chun
authors: IC
authors: Chen
authors: Aij-Lie
authors: AL
authors: Kwan
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009409:Nerve Crush / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries; D014970:Xanthines / Q000627:therapeutic use*
chemical_list: D010880:Piperidines; D014970:Xanthines; C439304:KMUP 1; D020780:Matrix Metalloproteinase 9