The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage

Abstract

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.

Neutrophil-to-Lymphocyte Ratio as an Independent Predictor of In-Hospital Mortality in Patients with Acute Intracerebral Hemorrhage

“…Second, initial peripheral immune activation is observed approximately six hours after experimentally induced ICH. In our study, the median time interval between stroke onset and first assessment of NLR (admission NLR) was 4.3 h (25-75 IQR: 2.2-11.1 h), and other authors have reported median ICH onset to NLR assessment time intervals of ≈6 h [9,19]. Thus, calculation of this ratio at the moment of hospital admission might be too early to identify any peripheral immune changes induced by the ICH and might reflect the effects of the neural-immune crosstalk only on its initial upslope, thereby limiting its value as a predictor of in-hospital mortality and short-term outcome.…”

Natural killer cell deficiency experiences higher risk of sepsis after critical intracerebral hemorrhage

“…13 Stroke-associated immune suppression might inhibit the overwhelming brain inflammation but increase the risk of systemic infection because of the disruption of immune defense. 14,15 The current study adds that immune modulators, such as fingolimod or immunoglobulin, should be administered early in ICH, as long-term use may exacerbate immune suppression. 16,17 Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections.…”

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

“…Another point of contention is the possibility that these related molecules may be derived from other immune cells described abobe. In our ICH mouse model, the macrophage responses would begin within a few hours after onset, and then the lymphocyte response begins on around Day 3 and later [ 64 ]. As the therapeutic window of our study was Days 1–3 after the onset of ICH, we speculated that macrophages would be the main source of these molecules during this period.…”