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

Hozo Matsuoka,Hiroyuki Tanaka,Shunsuke Nishimoto,Kiyoshi Okada,Hideki Yoshikawa,Tsuyoshi Murase,Toru Iwahashi,Koji Suzuki,Junichi Sayanagi

doi:10.3390/ijms19020516

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.

Highlights

Peripheral nerve injury (PNI) has a high incidence rate of 2.8% of all traumas [1]
We observed that NTP significantly increased AKT activity (Figure 1A) and suppressed ERK1/2 (Figure 1B) and p38 (Figure 1C) activities in Schwann cells (SCs) in a dose-dependent manner
NTP temporarily led to a 1.91 ± 0.06-fold stronger activation of AKT 5 min after NTP addition than that observed in the control (Figure 1F), and a 0.19 ± 0.05-fold weaker activation of ERK1/2 at 60 min than that in the control (Figure 1G)

Summary

Introduction

Nerve regeneration after injury is still a challenge. Regeneration after PNI is not necessarily complete, even when the injured nerves are microsurgically repaired. This often results in delayed recovery of motor and/or sensory function in patients who have sustained nerve injuries. This is the case in older patients, and after chronic denervation or injuries to large peripheral nerve trunks, such as the brachial plexus and the lumbar plexus [2,3,4,5]. Successful regeneration of injured peripheral nerves is challenging but has been an area of intense research

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