Data_Sheet_1_The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage.PDF

Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood–brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.

临床前与临床研究均已证实，炎症是调控脑出血（intracerebral hemorrhage, ICH）诱导性脑损伤的关键因素。越来越多的证据表明，髓系细胞与淋巴细胞参与了ICH相关的病理生理过程，包括炎症反应、免疫应答、血肿周围水肿形成、血脑屏障（blood–brain barrier, BBB）完整性维持以及细胞死亡。然而，其背后的潜在机制仍未完全阐明。本研究旨在探究免疫细胞在ICH不同病程阶段的作用。为此，我们采用新型生物信息学算法分析基因表达谱，并通过三种不同的分析工具预测细胞类型丰度。本研究发现，自然杀伤（natural killer, NK）细胞会在ICH发生后浸润至脑实质。浸润的NK细胞可能通过脱颗粒作用以及招募其他细胞介导脑损伤。此外，在ICH急性期，外周血单核细胞会执行吞噬功能并分泌细胞因子。而在亚急性期，非经典单核细胞会被激活，展现出更强的血红素代谢、伤口愈合以及抗原加工提呈能力。综上，本研究结果强调了脑内浸润免疫细胞在ICH中的重要意义，并证实ICH是一种受外周血影响的全身性疾病。本研究鉴定的核心基因有望成为极具前景的治疗靶点。同时，本研究也为利用生物信息学方法探索非肿瘤性免疫相关疾病提供了参考依据。