title: Dose-dependent effects of erythropoietin in propofol anesthetized neonatal rats.
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.
authors.affiliation: 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
authors.forename: Robert
authors.initials: R
authors.lastname: Zacharias
authors.forename: Maren
authors.initials: M
authors.lastname: Schmidt
authors.forename: Jenny
authors.initials: J
authors.lastname: Kny
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
authors.forename: Sven
authors.initials: S
authors.lastname: Bercker
authors.forename: Petra
authors.initials: P
authors.lastname: Bittigau
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Müser
authors.forename: Thoralf
authors.initials: T
authors.lastname: Kerner
mesh_terms: 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
chemical_list: D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D004921:Erythropoietin; D015742:Propofol