The neuroprotective effect of erythropoietin on spinal motor neurons after nerve root avulsion injury in rats

Restor Neurol Neurosci. 2015;33(4):461-70. doi: 10.3233/RNN-140481.

Abstract

Purpose: The rapid death of many spinal motor neurons after nerve root avulsion injury results in limited functional recovery following replantation surgery of avulsed nerves into the spinal cord. Therefore, we investigated the neuroprotective effect of erythropoietin (EPO) on motor neurons after nerve root avulsion injury using a rat model.

Methods: After C6 nerve root avulsion injury, EPO (2680 U/kg) was injected subcutaneously once a day for 3 consecutive days with various starting time points. At 28 and 56 days after injury, histological and immunohistological investigations were performed.

Results: EPO-treated rats showed a significant increase in the number of surviving motor neurons at day 28 when the initial dose was started within 96 h after injury. In EPO-treated rats, superoxide formation in the motor neurons and proliferation of microglia were markedly suppressed in the acute phase. GAP-43-positive surviving motor neurons were significantly increased in EPO-treated rats at day 28. However, at 56 days after surgery, EPO-treated rats showed a much greater decrease of surviving motor neurons compared with those at day 28.

Conclusion: The neuroprotective effect of EPO is not long lasting, but may prolong the time before replantation surgery.

Keywords: Nerve root avulsion injury; erythropoietin; motor neurons; oxidative stress; rat.

MeSH terms

  • Acute Disease
  • Animals
  • Cell Survival / drug effects
  • Cervical Vertebrae
  • Chronic Disease
  • Disease Models, Animal
  • Erythropoietin / administration & dosage*
  • Injections, Subcutaneous
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • Microglia / physiology
  • Motor Neurons / drug effects*
  • Motor Neurons / pathology
  • Motor Neurons / physiology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Neuroprotective Agents / administration & dosage*
  • Radiculopathy / drug therapy*
  • Radiculopathy / pathology
  • Radiculopathy / physiopathology
  • Random Allocation
  • Rats, Sprague-Dawley
  • Receptors, Erythropoietin / metabolism
  • Spinal Cord / drug effects*
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Superoxides / metabolism
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Receptors, Erythropoietin
  • Superoxides
  • Erythropoietin