Gene Expression Profile of Peripheral Blood Mononuclear Cells in Response to Intracerebral Hemorrhage

Abstract

RNA-sequencing, a powerful tool, yields a comprehensive view of whole transcriptome. Intracerebral hemorrhage (ICH) is a devastating form of stroke. To date, RNA-sequencing analysis of ICH has not been reported. Peripheral blood mononuclear cells (PBMCs) were used as a source of mRNA for gene expression profile analysis in stroke. In this study, we performed transcriptome analyses for PBMCs from four ICH patients and four healthy volunteers on Illumina platform. We identified 4040 significantly differentially expressed genes (DEGs). Functional annotation of DEGs with DAVID Bioinformatics Resources indicated that genes associated with cell apoptosis, autophagy, cell-cell adhesion, inflammatory response, protein binding, positive regulation of gene expression, and signal transduction were most significantly enriched by DEGs. Gene set enrichment analysis identified 40 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including chemokine signaling, cytokine-cytokine receptor interaction, oxidative phosphorylation, and glutathione metabolism processes. These data point to a complex mechanism for ICH pathogenesis. Overall, the present study demonstrated an altered gene expression profile of PBMCs in response to acute ICH. Our study provided important information for understanding the molecular mechanisms of ICH pathogenesis at system-wide levels.

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

“…Consistent with our results, ALOX5AP is found to increase in the acute phase of ICH (Rosell et al, 2011;Walsh et al, 2019). Besides, there are two studies, whose samples are taken during 3h and 24h after the onset of ICH, showing that ALOX5AP and Cyp1b1 is significant increased in this very early stage of ICH (Carmichael et al, 2008;Sang et al, 2017). This may hint that the up-regulation of ALOX5AP and Cyp1b1 can sustain through the acute phase of ICH.…”

“…There is still no research providing full information on the expression pattern of oxylipin relative enzymes in ICH, thus transcriptome studies related to ICH such as RNA-seq and microarray can be an alternative source. Nevertheless, only a few studies contain such information and the profiles of oxylipins relative enzymes in each study are different (Carmichael et al, 2008;Rosell et al, 2011;Sang et al, 2017;Walsh et al, 2019). Some researchers have also used peripheral blood mononuclear cells as a source of mRNA for gene expression profile analysis instead of perihematomal tissues, but these studies do provide important clues on the change in oxylipin relative enzymes in ICH (Sang et al, 2017;Walsh et al, 2019).…”

“…Nevertheless, only a few studies contain such information and the profiles of oxylipins relative enzymes in each study are different (Carmichael et al, 2008;Rosell et al, 2011;Sang et al, 2017;Walsh et al, 2019). Some researchers have also used peripheral blood mononuclear cells as a source of mRNA for gene expression profile analysis instead of perihematomal tissues, but these studies do provide important clues on the change in oxylipin relative enzymes in ICH (Sang et al, 2017;Walsh et al, 2019). Substantial peripheral inflammatory cells will infiltrate into the brain through the breakdown of the blood-brain barrier (BBB) and are involved in the ICH-induced inflammatory response (Xiong and Yang, 2015).…”

The intracerebral hemorrhage blood transcriptome in humans differs from the ischemic stroke and vascular risk factor control blood transcriptomes

“…10–13 Though the peripheral immune response has been studied extensively in human IS, 11,14–17 little is known about gene expression changes following ICH. 16,18 In addition, little is known about the alternatively spliced transcriptome of peripheral blood cells following ICH and IS. 14,16,18 Alternative splicing is the process by which a single gene produces multiple RNA transcripts and protein isoforms with different but related functions.…”

Intracerebral hemorrhage induces monocyte-related gene expression within six hours: Global transcriptional profiling in swine ICH

“…Although there is substantial interest in neuroinflammation as a therapeutic target following ICH, these processes remain poorly understood. Evidence exists for rapid local and systemic ICH inflammatory effects, with changes in human mononuclear gene expression within 3 h, (Sang et al 2017) and in the perihematomal region of swine ICH, cerebral edema, serum protein accumulation, and metabolic changes within one hour. (Wagner et al 1998) Peripheral blood mononuclear cell (PBMC) gene expression studies have shown promise in other neurological disorders such as ischemic stroke and seizures.…”