Metabolome and transcriptome integration reveals cerebral cortical metabolic profiles in rats with subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is a severe subtype of hemorrhagic stroke. The molecular mechanisms of its secondary brain damage remain obscure. To investigate the alterations in gene and metabolite levels following SAH, we construct the transcriptome and metabolome profiles of the rat cerebral cortex post-SAH using whole transcriptome sequencing and untargeted metabolomics assays. Transcriptomic analysis indicated that there were 982 differentially expressed genes (DEGs) and 540 differentially expressed metabolites (DEMs) between the sham group and SAH 1d, and 292 DEGs and 254 DEMs between SAH 1d and SAH 7d. Most notably, DEGs were predominantly involved in the activation of immune and inflammatory pathways, particularly the Complement and coagulation cascades, TNF signaling pathway, and NOD-like receptor signaling pathway. Metabolic analysis revealed that the metabolic pathways of Arginine and proline, Arachidonic acid, Folate biosynthesis, Pyrimidine, and Cysteine and methionine were remarkably affected after SAH. Metabolites of the above pathways are closely associated not only with immune inflammation but also with oxidative stress, endothelial cell damage, and blood–brain barrier disruption. This study provides new insights into the underlying pathologic mechanisms of secondary brain injury after SAH and further characterization of these aberrant signals could enable their application as potential therapeutic targets for SAH.