Table_9_Metabolome and transcriptome integration reveals cerebral cortical metabolic profiles in rats with subarachnoid hemorrhage.XLS

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.

蛛网膜下腔出血（Subarachnoid hemorrhage, SAH）是出血性脑卒中的危重亚型，其继发性脑损伤的分子机制至今尚未阐明。为探究蛛网膜下腔出血后基因与代谢物水平的变化，我们通过全转录组测序与非靶向代谢组学实验，构建了大鼠蛛网膜下腔出血后大脑皮层的转录组与代谢组图谱。转录组分析结果显示，假手术组与SAH造模后1天组间存在982个差异表达基因（differentially expressed genes, DEGs）与540个差异代谢物（differentially expressed metabolites, DEMs）；SAH造模后1天组与7天组间则存在292个差异表达基因与254个差异代谢物。尤为值得关注的是，差异表达基因主要富集于免疫与炎症通路的激活过程，尤其集中在补体与凝血级联反应、TNF信号通路以及NOD样受体信号通路。代谢组分析表明，精氨酸与脯氨酸代谢、花生四烯酸代谢、叶酸生物合成、嘧啶代谢以及半胱氨酸与蛋氨酸代谢通路在SAH后发生显著改变。上述通路中的代谢物不仅与免疫炎症反应紧密相关，还参与氧化应激、内皮细胞损伤及血脑屏障破坏等病理过程。本研究为揭示蛛网膜下腔出血后继发性脑损伤的潜在病理机制提供了新的视角，对这些异常信号的进一步表征有望将其开发为SAH潜在的治疗靶点。