Temporal and spatial transcriptomic analysis of neutrophils and monocyte/macrophages in intracerebral hemorrhage

Abstract Background and aim: Intracerebral hemorrhage (ICH) is a devastating stroke, in which inflammation plays an important role. We aim to understand the functions of neutrophils and monocyte/macrophage in inflammation of ICH. Materials and Methods: We comprehensively analyzed a publically-available transcriptomic dataset (GSE163256) at spatial and temporal levels. A gene co-expression network algorithm combined with Kpca algorithm was used to pinpoint the effective gene modules when setting the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Glasgow Coma Scale (GCS) as outcome, and recognize the hub genes that influence the ICH prognosis when setting mRS as outcome. The logistic regression analysis was then conducted to identify the key genes. Results: In both peripheral blood (PB) and hematoma, cytokine-mediated signaling in neutrophils was associated with GCS; cytokine-mediated signaling processes and innate immune response processes in neutrophils were associated with NIHSS and mRS, respectively; energy metabolism in monocyte/macrophages was associated with NIHSS. In hematoma, leukocyte activation and migration in monocyte/macrophages correlated with GCS, while inflammation-related pathways correlated with mRS. Moreover, neutrophils experienced cytokine modulation and leukocyte-mediated immune responses, monocyte/macrophages underwent NF-κB-mediated immune responses in early ICH. The key genes included NCF1 , GPSM3 , STEAP4 , ABDH16A , and PTPRC in neutrophils and NHP2 , UPP1 , CYBB , IDH1 , and ZC3H12A in monocyte/macrophages. Conclusion : Our findings suggest a mechanism involving inflammation in ICH, in which neutrophils are activated in PB and hematoma, which in turn recruit monocytes into hematoma where they differentiate to macrophages and are activated to promote inflammation, contributing to secondary brain injury.