Combination Treatment With Exogenous GDNF and Fetal Spinal Cord Cells Results in Better Motoneuron Survival and Functional Recovery After Avulsion Injury With Delayed Root Reimplantation

J Neuropathol Exp Neurol. 2018 Apr 1;77(4):325-343. doi: 10.1093/jnen/nly009.

Abstract

When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation. Application of exogenous GDNF to injured spinal cord greatly prevented the motoneuron death and enhanced the regeneration and axonal sprouting, whereas no effect was seen on the functional recovery. In contrast, cell transplantation into the distal nerve did not affect the host motoneurons but instead mitigated the muscle atrophy. The combination of GDNF and cell graft reunited the positive effects resulting in better functional recovery and could therefore be considered as a promising strategy for nerve and spinal cord injuries that involve the avulsion of spinal roots.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Choline O-Acetyltransferase / metabolism
  • Embryo, Mammalian
  • Female
  • Fetal Stem Cells / physiology
  • Fetal Stem Cells / transplantation*
  • Glial Cell Line-Derived Neurotrophic Factor / therapeutic use*
  • Grooming / physiology
  • Homeodomain Proteins / metabolism
  • Motor Neurons / physiology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myelin Sheath / metabolism
  • Nerve Regeneration
  • Neurofilament Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Replantation
  • Spinal Cord / cytology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / surgery*
  • Tubulin / metabolism

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Homeodomain Proteins
  • Neurofilament Proteins
  • Tubulin
  • neurofilament protein H
  • Choline O-Acetyltransferase