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01-10-2012 | Experimental research

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

Authors: Chia-Li Chung, Hung-Pei Tsai, Kung-Shing Lee, Kuang-I Chen, Shu-Chuan Wu, Yen-Hsin Kuo, William Winardi, Ing-Chun Chen, Aij-Lie Kwan

Published in: Acta Neurochirurgica | Issue 10/2012

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 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; 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, 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.

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Title: 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
Authors: Chia-Li Chung
Hung-Pei Tsai
Kung-Shing Lee
Kuang-I Chen
Shu-Chuan Wu
Yen-Hsin Kuo
William Winardi
Ing-Chun Chen
Aij-Lie Kwan
Publication date: 01-10-2012
Publisher: Springer Vienna
Published in: Acta Neurochirurgica / Issue 10/2012
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI: https://doi.org/10.1007/s00701-012-1433-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Method

Findings

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Method

Findings

Conclusions

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