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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

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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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Conflicts of interest

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Authors and Affiliations

  1. Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chia-Li Chung

  2. Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan

    Chia-Li Chung & Kung-Shing Lee

  3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Pei Tsai & Yen-Hsin Kuo

  4. Department of Anesthesiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Kuang-I Chen

  5. Division of Anesthesiology, Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Kuang-I Chen

  6. Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Shu-Chuan Wu & Aij-Lie Kwan

  7. Poznan University of Medical Sciences, Poznan, Poland

    William Winardi

  8. Department of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ing-Chun Chen

  9. Department of Neurosurgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, 100 Shih-Chuan First Road, Kaohsiung, Taiwan, Republic of China

    Aij-Lie Kwan

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  1. Chia-Li Chung
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Correspondence to Aij-Lie Kwan.

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Chung, CL., Tsai, HP., Lee, KS. et al. 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. Acta Neurochir 154, 1773–1779 (2012). https://doi.org/10.1007/s00701-012-1433-y

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  • DOI: https://doi.org/10.1007/s00701-012-1433-y

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