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Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats

  • Gang Li
  • Zhong-Kai Fan
  • Guang-Fei Gu
  • Zhi-Qiang Jia
  • Qiang-Qiang Zhang
  • Jun-Yu Dai
  • Shi-Sheng HeEmail author
Original Article
  • 91 Downloads

Abstract

Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.

Keywords

Spinal cord injury Epidural spinal cord stimulation Oligodendrocyte Differentiation Remyelination 

Notes

Acknowledgements

This research was supported by the Natural Science Foundation of Liaoning Province (201602277), and the Science and Technology Planning Project of Liaoning Province (LJQ2014091). We thank Barry Patel, PhD, for editing the English text of a draft of this manuscript.

Conflict of interest

The authors declare that they have no conflicts of interest, financial or otherwise.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Gang Li
    • 1
    • 2
  • Zhong-Kai Fan
    • 3
  • Guang-Fei Gu
    • 1
    • 2
  • Zhi-Qiang Jia
    • 4
  • Qiang-Qiang Zhang
    • 3
  • Jun-Yu Dai
    • 3
  • Shi-Sheng He
    • 1
    • 2
    Email author
  1. 1.Department of Orthopedics, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  2. 2.Spinal Pain Research InstituteTongji University School of MedicineShanghaiChina
  3. 3.Department of Orthopaedics, The First Affiliated HospitalJinzhou Medical UniversityJinzhouChina
  4. 4.Department of Spinal Surgery, The Second Affiliated HospitalHenan University of Science and TechnologyLuoyangChina

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