Dose-dependent Effects of Erythropoietin in Propofol Anesthetized Neonatal Rats

Brain Res. 2010 Jul 9;1343:14-9. doi: 10.1016/j.brainres.2010.04.081. Epub 2010 May 7.

Abstract

Exposure to Gamma-aminobutyric-acid (GABA)(A)-receptor agonists and N-Methyl-D-Aspartate (NMDA)-antagonists has been demonstrated to induce neurodegeneration in newborn rats. Exogenous erythropoietin (EPO) protects against NMDA antagonist-mediated neuronal death. In this study we evaluated whether EPO is also effective in limiting neurodegeneration of the GABA(A)-mimetic agent propofol in newborn rats. 6 day old rats were randomized to one of four groups and treated with intraperitoneal applications of 3 x 30 mg/kg propofol at 0, 90 and 180 min, propofol in combination with 5000 IU/kg rEPO, propofol in combination with 20,000 IU/kg rEPO or sham injections of PAD II solution as controls. After 24h, brains of the animals were histopathologically examined and a summation score of degenerated cells was calculated for every brain. Propofol increased neuronal degeneration scores from 16,090+/-4336 to 28,860+/-6569 (p<0.01). This effect was completely abolished by low-dose rEPO (14,270+/-4542, p<0.001 versus propofol only; p>0.05 versus controls). In contrast, high-dose rEPO was not protective (23 930+/-8896, p>0.05 versus propofol only). Propofol may cause neuronal death in newborn rat brains, which is prevented by low-dose rEPO but not high-dose rEPO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Erythropoietin / administration & dosage*
  • Erythropoietin / therapeutic use
  • Hypnotics and Sedatives / antagonists & inhibitors*
  • Hypnotics and Sedatives / toxicity
  • Injections, Intraperitoneal
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / prevention & control
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Propofol / antagonists & inhibitors*
  • Propofol / toxicity
  • Rats
  • Treatment Outcome

Substances

  • Hypnotics and Sedatives
  • Neuroprotective Agents
  • Erythropoietin
  • Propofol