Dose-dependent effects of erythropoietin in propofol anesthetized neonatal rats

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 GABAA-mimetic agent propofol in newborn rats. 6 day old rats were randomized to one of four groups and treated with intraperitoneal applications of 3 × 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 PÄD II solution as controls. After 24 h, 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.