Transcriptomic Profiles of Sepsis in the Human Brain

The purpose of this study is to examine the transcriptomic profiles (RNAseq) of post-mortem brain tissue samples from patients who have died of sepsis compared to non-sepsis controls using two analytic approaches. Tissue samples originated from the Adult Changes in Thought study (ACT) brain bank. In order to determine cause of death, hospital charts for 89 ACT subjects who died while hospitalized were reviewed using a structured instrument for diagnosis of sepsis. RNA was extracted from 24 post-mortem parietal cortex tissue samples. RNA sequencing was performed on the 24 samples using Illumina's Hi-Seq platform. Raw data was exported, pre-processed, and analyzed by two methods, differential expression and weighted gene co-expression network analysis (WGCNA). 176 genes were differentially expressed with fold change of > 1.5 and adjusted p < 0.5. The top differentially expressed genes were immune-related. WGCNA reveled 6 modules were significantly correlated with sepsis. Significant nodules were enriched in terms associated with innate immunity, cytokines, DAMPs, synaptic function, ion channel function, neuronal growth, and T-cell signalling among others. These data suggest sepsis is associated with specific transcriptional responses in the human brain. These results provide support for previously identified targets as well as provide evidence to suggest investigation into new targets for mechanistic exploration of sepsis-associated brain injury. Overall design: RNAseq data was generated from post-mortem human brain tissue samples from Sepsis cases and non-sepsis controls.