Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain A randomised placebo-controlled experimental in-vivo study

BACKGROUND Recent experimental data indicate that volatile anaesthetics can induce a neuroinflammatory response in the central nervous system. The questions of to what extent this occurs in the developing brain and whether nonvolatile anaesthetics are also involved remain unanswered. OBJECTIVES The objective of this study is to investigate the impact of propofol anaesthesia on cytokine mRNA expression profiles in the neonatal brain at defined stages of the brain growth spurt. DESIGN A randomised placebo-controlled experimental in-vivo study. SETTING Translational research laboratories at the University of Geneva Medical School. METHODS Wistar rats received 6-h propofol anaesthesia at postnatal day 10 or 20. A quantitative real-time PCR was used to evaluate the impact of this treatment paradigm on mRNA expression profiles of selected members of the cytokine family in the prefrontal cortex and hippocampus. RESULTS Propofol anaesthesia induced a transient 1.8-fold (interquartile range, IQR 1.7 to 2.2) increase (P = 0.004) in prefrontal but not hippocampal tumour necrosis factor mRNA concentrations in 10-day-old animals. No such effect was detected in 20-day-old animals. No changes in mRNA concentrations of two other pro-inflammatory cytokines, interleukins IL-6 and IL-1b, were detected following drug exposure at any developmental stages or in any studied brain regions. In contrast, propofol anaesthesia at postnatal day 10 induced a transient increase in the mRNA expression patterns of two chemokines: Ccl2 and Ccl3 [for Ccl2 mRNA: 4.4-fold (3.8 to 5.6) increase in the prefrontal cortex, P = 0.0002 and a 3.5-fold (2.8 to 5.3) increase in the hippocampus, P = 0.0001; for Ccl3mRNA: 2.9-fold (2.6 to 4.31) increase in the prefrontal cortex, P = 0.0001, and a 2.7-fold (2.2 to 3.6) increase in the hippocampus, P = 0.0003]. Propofol did not affect Ccl2 and Ccl3 mRNA concentrations in 20-day-old animals. In addition, it did not impact on two other members of the chemokine family, Cxcl1 and Cx3cl1, at any time points or in any brain regions investigated. CONCLUSION This study suggests that propofol anaesthesia does not have a major impact on pro-inflammatory cytokine expression profiles in the developing central nervous system during the brain growth spurt. These results raise arguments against the involvement of neuroinflammatory pathways in propofol-related neurotoxicity observed following the administration of this drug in the early postnatal period.