Background: Secondary brain injury following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is life threatening, and effective therapeutic strategies are lacking. This study aimed to understand the molecular pathogenesis of ICH- or SAH-induced secondary brain injury and provide insights regarding potential therapeutic options.
Methods: Original data of tissue microarray studies were downloaded from the Gene Expression Omnibus database. We identified the differentially expressed genes (DEGs) for each disease and common DEGs between ICH and SAH. Functional enrichment analyses were then analyzed, and a protein-protein interaction network was constructed to strictly select hub genes. Additionally, immune infiltration analyses were used to identify the common differently distributed cells in both diseases. Finally, animal model microarrays were used for external validation.
Results: We identified 158 common DEGs. The common DEGs were significantly enriched in cytotoxicity and inflammation pathways. The top 10 hub genes were then filtered through the protein-protein interaction networks. Moreover, natural regulatory T, T helper 17, and dendritic cells and monocytes and macrophages were identified as common differentially distributed immune cells. Additionally, target microRNAs and related drugs of hub genes were predicted.
Conclusions: This study identified a variety of key genes and their respective molecular functions involved in both ICH and SAH for better understanding of the cytotoxic and inflammatory pathogenesis of secondary brain injury. The predicted targeted microRNAs and related drugs of hub genes not only could provide insights into the novel therapeutic strategies, but also could aid in future studies and drug discovery.
Keywords: Bioinformatic analysis; Gene expression omnibus; Intracerebral hemorrhage; Secondary brain injury; Subarachnoid hemorrhage.
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