Intracerebral Hemorrhage Induces Inflammatory Gene Expression in Peripheral Blood: Global Transcriptional Profiling in ICH Patients

Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. While there is substantial interest in post-ICH neuroinflammation and associated pathophysiological mechanisms, these processes remain poorly understood. To further advance our understanding, we performed RNA-seq in the peripheral blood of ICH patients to test the hypothesis that ICH would induce inflammatory biological pathways. 16,640 genes were identified and 216 were significant DEGs after ICH (FDR<0.1). IPA identified three canonical pathways as the most statistically significantly activated by ICH: colorectal cancer metastasis signaling (Z-score 3.00, P=1.71E-5), interleukin-8 (IL-8) signaling (3.00, 8.44E-5), and nuclear factor-kappa B (NF-kB) activation by viruses (2.55, 1.78E-4). Inflammatory mediators of particular relevance included IL-8, NF-kB, ERK 1/2, and the integrins ß3, a2b, and ß5. Conclusion: ICH induced peripheral blood gene expression at 72 to 96 hours compared with 0 to 24 hours from symptom onset. DEGs that were highly expressed in the significant biological pathways included those related to inflammation and activation of the immune response. Further research is needed to determine if these changes affect outcomes and may represent new therapeutic targets. Overall design: In 11 patients with ICH, the first peripheral blood sample was collected within 24 hours of symptom onset or last known well, and a second blood draw occurred 72 hours (+ 6) following the first. RNA-seq was conducted to identify differentially expressed genes (DEGs) between the first and second samples. Biological pathway enrichment analysis was performed with Ingenuity® Pathway Analysis (IPA).