Gene Expression Changes Implicate Specific Peripheral Immune Responses to Deep and Lobar Intracerebral Hemorrhages in Humans

The peripheral immune system response to Intracerebral Hemorrhage (ICH) may differ with ICH in different brain locations. Thus, we investigated peripheral blood mRNA expression of Deep ICH, Lobar ICH, and vascular risk factor-matched control subjects (n = 59). Deep ICH subjects usually had hypertension. Some Lobar ICH subjects had cerebral amyloid angiopathy (CAA). Genes and gene networks in Deep ICH and Lobar ICH were compared to controls. We found 774 differentially expressed genes (DEGs) and 2 co-expressed gene modules associated with Deep ICH, and 441 DEGs and 5 modules associated with Lobar ICH. Pathway enrichment showed some common immune/inflammatory responses between locations including Autophagy, T Cell Receptor, Inflammasome, and Neuroinflammation Signaling. Th2, Interferon, GP6, and BEX2 Signaling were unique to Deep ICH. Necroptosis Signaling, Protein Ubiquitination, Amyloid Processing, and various RNA Processing terms were unique to Lobar ICH. Finding amyloid processing pathways in blood of Lobar ICH patients suggests peripheral immune cells may participate in processes leading to perivascular/vascular amyloid in CAA vessels and/or are involved in its removal. This study identifies distinct peripheral blood transcriptome architectures in Deep and Lobar ICH, emphasizes the need for considering location in ICH studies/clinical trials, and presents potential location-specific treatment targets.