GSE124624
ICH Induces Monocyte-Related Gene Expression Within Six Hours; A Study of Global Transcriptional Profiling in Swine ICH
Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Our prior research identified a significant association with monocyte level and ICH mortality. To further advance our understanding, we sought to identify the gene expression changes after ICH using a swine model to test the hypothesis that ICH would result in changes in peripheral blood mononuclear cell (PBMC) gene expression.  There were 182 significantly upregulated and 153 significantly down-regulated DEGs after ICH. Consistent with findings in humans, significant GO and KEGG pathways were those primarily related to inflammation, immune response, and response to infectious pathogens. There were five genes, all with increased expression post-ICH, that were repeatedly identified as significant DEGs in the statistically significant KEGG pathways:  CD14 (cluster of differentiation 14), TLR4 (toll-like receptor-4), CXCL8 (CXC motif chemokine-8), IL-18 (interleukin-18), and CXCL2 (CXC motif chemokine-2).  Conclusion:  ICH induced changes in PBMC gene expression within 6 hours of onset. DEGs that were highly expressed in the significant biological pathways included those related to inflammation, the immune response, and, more specifically, monocyte activation. Further research is needed to determine if these changes affect outcomes and may represent new therapeutic targets. Overall design: In 10 pigs with autologous blood injection to induce ICH, two PBMC samples were drawn from each pig with the first immediately prior to ICH induction and the second 6 hours later. RNA-seq was performed to identify differentially expressed genes (DEGs) and associated Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.