Re-exploring the inflammation-related core genes and modules in cerebral ischemia

Abstract

The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed genes (DEGs) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological processes analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO), and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). We identified reperfusion as the main confounding factor in gene profile changes. Our analyses of pathway and biological processes revealed upregulated functional modules involved in inflammatory disequilibrium and thrombus formation. Astrocytes, microglia, and macrophages were the main contributors of inflammation-related gene changes. Novel core hubs implicated in negative regulation of inflammation (Zfp36, Nfkbiz, and Maff) were identified and validated. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.