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 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.
Zacharias
Robert
R
Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin, Campus Virchow-Klinikum und Charité Campus Mitte, Charité Centrum 7 für Anästhesiologie, OP-Management und Intensivmedizin, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany. robert.zacharias@charite.de
Schmidt
Maren
M
Kny
Jenny
J
Sifringer
Marco
M
Bercker
Sven
S
Bittigau
Petra
P
Bührer
Christoph
C
Felderhoff-Müser
Ursula
U
Kerner
Thoralf
T
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015742:Propofol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D016896:Treatment Outcome
D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D004921:Erythropoietin; D015742:Propofol