113 The Apoptotic Effect of Propofol in Immature Rat Brain and Possible Neuroprotection by Erythropoietin

Background: Propofol is a frequently used drug in pediatric anesthesia and neonatology. We have recently shown that exposure of rodent pups by propofol induces neuronal apoptosis in short term.Aim: The aim of the current investigation is to evaluatea) mechanisms of propofol induced neurotoxicity andb) whether the neurotoxic effect can be reduced by ErythropoietinMethods: Newborn rats were randomized into following groups i) sham ii) Propofol iii) Propofol with Erythropoietin intraperitoneal injections. Animals were killed after 6, 12, and 24 hours and the brains were harvested for gene (Affymetrix Chip) and protein expression (Western Blot) analyses.Results: Propofol induces caspase-3 activation which was inhibited by systemic treatment with EPO at 12 hours. Primary results of gene expression array analyses indicate that systemic Propofol administration induces a reduction in genes involved in Ca2+-regulatory mechanism as well as phosphoinositide-3-kinase signaling. In western blots analyses Propofol induced a transient activation of pAkt, which was increased by co-administration of EPO. In addition Propofol administration decraesed cytokine IL-18 brain levels.Conclusion: Administration of Propofol does not only induces neuronal cell death but also induces major modification in cellular signalling in the developing brain. Cell death induced by Propofol is reduced by co-administration of EPO. Additional investigations analysing the effect of propofol on long-term behavioural outcome and mechanisms of action are mandatory and ongoing.