Ageing and genetic background influence anaesthetic effects in a D. melanogaster model of blunt trauma with brain injury

backgroundGeneral anaesthetics interact with the pathophysiological mechanisms of traumatic brain injury (TBI). We used a Drosophila melanogaster (fruit fly) model to test the hypothesis that ageing and genetic background modulate the effect of anaesthetics and hyperoxia on TBI-induced mortality in the context of blunt trauma.

methodsWe exposed flies to isoflurane or sevoflurane under normoxic or hyperoxic conditions and TBI, and subsequently quantified the effect on mortality 24 h after injury. To determine the effect of age on anaesthetic-induced mortality, we analysed flies at 1-8 and 43-50 days old. To determine the effect of genetic background, we performed a genome-wide association study (GWAS) analysis on a collection of young inbred, fully sequenced lines.

resultsExposure to anaesthetics and hyperoxia differentially affected mortality in young and old flies. Pre-exposure of young but not old flies to anaesthetics reduced mortality. Post-exposure selectively increased mortality. For old but not young flies, hyperoxia enhanced the effect on mortality of post-exposure to isoflurane but not to sevoflurane. Post-exposure to isoflurane in hyperoxia increased the mortality of young fly lines in the Drosophila Genetic Reference Panel collection to different extents. GWAS analysis of these data identified single nucleotide polymorphisms in genes involved in cell water regulation and oxygen sensing as being associated with the post-exposure effect on mortality.

conclusionsAgeing and genetic background influence the effects of volatile general anaesthetics and hyperoxia on mortality in the context of traumatic brain injury. Polymorphisms in specific genes are identified as potential causes of ageing and genetic effects.