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Abstract
Background and Aims Fetal asphyctic (FA) preconditioning has been shown to be effective in attenuating brain damage incurred by a subsequent perinatal asphyctic event. Unraveling mechanisms of this endogenous neuroprotection, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is, at least in part, responsible for the protective effect of preconditioning in the brain. Therefore we investigated differential gene expression with whole genome micro-array.
Methods FA preconditioning was induced on E17 by reversibly clamping the uterine circulation for 30 min. Perinatal asphyxia (PA) was induced at E21/22 by submersing the uterine horns including pups in a water bath for 19 minutes. Four experimental groups were sacrificed 6 and 96h after birth: Control, FA, PA, and preconditioned animals that underwent perinatal asphyxia (FAPA). Whole genome transcription was investigated with the Affymetrix Gene1.0ST chip and analyzed with the Bioconductor Limma package.
Results Figure 1 and 2 depict the number of differentially regulated transcripts respectively 6 and 96 hours after birth.
Number of differentially expressed transcripts compared to control (p<0.01), 6h after birth
Number of differentially expressed transcripts compared to control (p<0.01), 96h after birth
Many of these transcripts are involved in synaptic transmission and metabolism. Interestingly, we also found changes in several histone clusters and histone deacetylases.
Conclusions This is the first study to investigate whole genome expression in a preconditioning and ashyxia model that includes the fetal-to-neonatal transition and therefore truly resembles perinatal asphyxia. Our results warrant further research into epigenetic mechanisms of neuroprotection.