PNNL

Abstract

CpG preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms that underlie genomic reprogramming are incompletely understood. MicroRNAs (miRNA) are novel regulators of gene expression; however, their potential role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning prior to and following stroke using microarray. Importantly, we have gene expression data from previous gene microarrays under the same conditions and timepoints, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. Statistical analysis revealed that the miRNA targets were enriched in our regulated gene population, implicating that miRNAs likely orchestrate this gene expression. CpG and saline treatment shared expression of many miRNAs and their gene targets correlate with damaging upregulation of inflammation and protective suppression of metabolism and excitotoxicity. Excitingly, miRNAs that were differentially regulated between CpG and saline treated animals associated with the upregulation of several neuroprotective genes, indicating that these miRNAs are involved in genomic reprogramming to increase protection. This data suggests that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel protective responses to stroke.