Elucidation of Gene Expression Patterns in the Brain after Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a devastating neurological disease. The pathophysiological mechanisms of SCI have been reported to be relevant to central nervous system injury such as brain injury. In this study, gene expression of the brain after SCI was elucidated using transcriptome analysis to characterize the temporal changes in global gene expression patterns in a SCI mouse model. Subjects were randomly classified into 3 groups: sham control, acute (3 h post-injury), and subacute (2 wk post-injury) groups. We sought to confirm the genes differentially expressed between post-injured groups and sham control group. Therefore, we performed transcriptome analysis to investigate the enriched pathways associated with pathophysiology of the brain after SCI using Database for Annotation Visualization, and Integrated Discovery (DAVID), which yielded Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Following enriched pathways were found in the brain: oxidative phosphorylation pathway; inflammatory response pathways-cytokine-cytokine receptor interaction and chemokine signaling pathway; and endoplasmic reticulum (ER) stress-related pathways-antigen processing and presentation and mitogen-activated protein kinase signaling pathway. Oxidative phosphorylation pathway was identified at acute phase, while inflammation response and ER stress-related pathways were identified at subacute phase. Since the following pathways-oxidative phosphorylation pathway, inflammatory response pathways, and ER stress-related pathways-have been well known in the SCI, we suggested a link between SCI and brain injury. These mechanisms provide valuable reference data for better understanding pathophysiological processes in the brain after SCI.