Original Article

GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons

  1. Liqun Zhang1,2,
  2. Zhengwen Ma1,
  3. George M. Smith3,
  4. Xuejun Wen4,
  5. Yelena Pressman5,
  6. Patrick M. Wood5,
  7. Xiao-Ming Xu1,6,*

Article first published online: 23 JAN 2009

DOI: 10.1002/glia.20840

Issue

Glia

Glia

Volume 57, Issue 11, pages 1178–1191, 15 August 2009

Additional Information

How to Cite

Zhang, L., Ma, Z., Smith, G. M., Wen, X., Pressman, Y., Wood, P. M. and Xu, X.-M. (2009), GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons. Glia, 57: 1178–1191. doi: 10.1002/glia.20840

Author Information

  1. 1

    Kentucky Spinal Cord Injury Research Center, Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky

  2. 2

    Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China

  3. 3

    Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky Chandler Medical Center, Lexington, Kentucky

  4. 4

    Clemson-MUSC Joint Bioengineering Program, Charleston, South Carolina

  5. 5

    The Miami Project to Cure Paralysis, Departments of Neurological Surgery, University of Miami School of Medicine, Miami, Florida

  6. 6

    Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana

*Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, 950 W. Walnut Street, R2-427, Indianapolis, IN 46202, USA

Publication History

  1. Issue published online: 1 JUL 2009
  2. Article first published online: 23 JAN 2009
  3. Manuscript Accepted: 4 DEC 2008
  4. Manuscript Received: 15 JUL 2008

Funded by

  • NIH. Grant Numbers: NS36350, NS52290, NS50243, NS09923, RR15576
  • Kentucky Spinal Cord and Head Injury Research Trust
  • Daniel Heumann Fund for Spinal Cord Research
  • James R. Petersdorf (University of Louisville)
  • Mari Hulman George (Indiana University) Endowments

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Keywords:

  • GDNF;
  • axon;
  • myelination;
  • regeneration;
  • Schwann cell;
  • spinal cord injury

Abstract

We previously demonstrated that coadministration of glial cell line-derived neurotrophic factor (GDNF) with grafts of Schwann cells (SCs) enhanced axonal regeneration and remyelination following spinal cord injury (SCI). However, the cellular target through which GDNF mediates such actions was unclear. Here, we report that GDNF enhanced both the number and caliber of regenerated axons in vivo and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) in vitro, suggesting that GDNF has a direct effect on neurons. In SC-DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF-enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. © 2009 Wiley-Liss, Inc.

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