Recombinant human erythropoietin decreases myeloperoxidase and caspase-3 activity and improves early functional results after spinal cord injury in rats

J Clin Neurosci. 2007 Apr;14(4):364-8. doi: 10.1016/j.jocn.2006.01.022. Epub 2007 Jan 22.

Abstract

Inflammatory response and apoptosis have been proposed as mechanisms of secondary injury of the spinal cord after primary insult. Recent studies have shown that erythropoietin (EPO) has neuroprotective properties. In this study, we assessed the efficacy of recombinant human erythropoietin (r-Hu-EPO) in the treatment of acute spinal cord injury (SCI) in rats. Rats were divided into five groups of eight rats each. Controls (Group 1) received laminectomy only. The trauma-only group (Group 2) underwent 40 g/cm contusion injury and had no medication. In group 3, 30 mg/kg of methylprednisolone (MPSS) was administered. Group 4 received 1000 IU/kg body weight of r-Hu-EPO. The vehicle group (Group 5) received a vehicle solution containing human serum albumin, which is the solvent for r-Hu-EPO. Twenty-four hours after trauma, animals were functionally evaluated and a spinal cord samples were obtained for the assessment of caspase-3 and myeloperoxidase (MPO) activities. The results showed that MPO and caspase-3 activities increased to statistically significant higher levels in the spinal cord after contusion injury comparing to the control group. MPO and caspase-3 enzyme activity levels were significantly reduced in animals treated either with r-Hu-EPO or MPSS. In addition, we observed significant early functional recovery in EPO-treated rats. EPO has anti-apoptotic and anti-inflammatory effects, and improves early clinical results after SCI.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism*
  • Erythropoietin / pharmacology*
  • Female
  • Humans
  • Methylprednisolone / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Peroxidase / drug effects
  • Peroxidase / metabolism*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Recovery of Function
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / enzymology*

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Recombinant Proteins
  • Erythropoietin
  • Peroxidase
  • Caspase 3
  • Methylprednisolone