Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury

J Mol Neurosci. 2016 Jan;58(1):39-45. doi: 10.1007/s12031-015-0648-9. Epub 2015 Sep 18.


Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury.

Keywords: Compound muscle action potential (CMAP); Conduction velocity; Nerve injury; Neurotrophic factors.

MeSH terms

  • Action Potentials
  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Brain-Derived Neurotrophic Factor / therapeutic use*
  • Cell Line
  • Genetic Therapy
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Glial Cell Line-Derived Neurotrophic Factor / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor I / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology
  • Nerve Regeneration / drug effects
  • Peripheral Nerve Injuries / drug therapy*
  • Recovery of Function
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiology
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor A / therapeutic use*


  • Brain-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I