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Article

Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model

by
Hozo Matsuoka
1,
Hiroyuki Tanaka
1,*,
Junichi Sayanagi
1,
Toru Iwahashi
1,
Koji Suzuki
2,
Shunsuke Nishimoto
2,
Kiyoshi Okada
1,3,
Tsuyoshi Murase
1 and
Hideki Yoshikawa
1
1
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
2
Department of Orthopaedic Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, Hyogo 660-0064, Japan
3
Medical Center for Translational and Clinical Research, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 516; https://doi.org/10.3390/ijms19020516
Submission received: 15 December 2017 / Revised: 21 January 2018 / Accepted: 3 February 2018 / Published: 8 February 2018
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside 2017)
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Abstract

Neurotropin® (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study was to investigate the effects of NTP on Schwann cells (SCs) in vitro and in vivo, which play an important role in peripheral nerve regeneration. In SCs, NTP upregulated protein kinase B (AKT) activity and Krox20 and downregulated extracellular signal-regulated kinase1/2 activity under both growth and differentiation conditions, enhanced the expression of myelin basic protein and protein zero under the differentiation condition. In a co-culture of dorsal root ganglion neurons and SCs, NTP accelerated myelination of SCs. To further investigate the influence of NTP on SCs in vivo, lysophosphatidylcholine was injected into the rat sciatic nerve, leading to the focal demyelination. After demyelination, NTP was administered systemically with an osmotic pump for one week. NTP improved the ratio of myelinated axons and motor, sensory, and electrophysiological function. These findings reveal novel effects of NTP on SCs differentiation in vitro and in vivo, and indicate NTP as a promising treatment option for peripheral nerve injuries and demyelinating diseases.
Keywords: Neurotropin®; Schwann cells; differentiation; AKT; extracellular signal-regulated kinase1/2; remyelination; peripheral nerve; regeneration Neurotropin®; Schwann cells; differentiation; AKT; extracellular signal-regulated kinase1/2; remyelination; peripheral nerve; regeneration
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MDPI and ACS Style

Matsuoka, H.; Tanaka, H.; Sayanagi, J.; Iwahashi, T.; Suzuki, K.; Nishimoto, S.; Okada, K.; Murase, T.; Yoshikawa, H. Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model. Int. J. Mol. Sci. 2018, 19, 516. https://doi.org/10.3390/ijms19020516

AMA Style

Matsuoka H, Tanaka H, Sayanagi J, Iwahashi T, Suzuki K, Nishimoto S, Okada K, Murase T, Yoshikawa H. Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model. International Journal of Molecular Sciences. 2018; 19(2):516. https://doi.org/10.3390/ijms19020516

Chicago/Turabian Style

Matsuoka, Hozo, Hiroyuki Tanaka, Junichi Sayanagi, Toru Iwahashi, Koji Suzuki, Shunsuke Nishimoto, Kiyoshi Okada, Tsuyoshi Murase, and Hideki Yoshikawa. 2018. "Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model" International Journal of Molecular Sciences 19, no. 2: 516. https://doi.org/10.3390/ijms19020516

APA Style

Matsuoka, H., Tanaka, H., Sayanagi, J., Iwahashi, T., Suzuki, K., Nishimoto, S., Okada, K., Murase, T., & Yoshikawa, H. (2018). Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model. International Journal of Molecular Sciences, 19(2), 516. https://doi.org/10.3390/ijms19020516

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