Distinct peripheral blood monocyte and neutrophil transcriptional programs following intracerebral hemorrhage and different etiologies of ischemic stroke

Abstract

Understanding cell-specific transcriptome responses following intracerebral hemorrhage (ICH) and ischemic stroke (IS) will improve knowledge of the immune response to brain injury. Transcriptomic profiles of 141 samples from 48 subjects with ICH, different IS etiologies, and vascular risk factor controls were characterized using RNA-seq in isolated neutrophils, monocytes and whole blood. In both IS and ICH, monocyte genes were down-regulated, whereas neutrophil gene expression changes were generally up-regulated. The monocyte down-regulated response to ICH included innate, adaptive immune, dendritic, NK cell and atherosclerosis signaling. Neutrophil responses to ICH included tRNA charging, mitochondrial dysfunction, and ER stress pathways. Common monocyte and neutrophil responses to ICH included interferon signaling, neuroinflammation, death receptor signaling, and NFAT pathways. Suppressed monocyte responses to IS included interferon and dendritic cell maturation signaling, phagosome formation, and IL-15 signaling. Activated neutrophil responses to IS included oxidative phosphorylation, mTOR, BMP, growth factor signaling, and calpain proteases-mediated blood–brain barrier (BBB) dysfunction. Common monocyte and neutrophil responses to IS included JAK1, JAK3, STAT3, and thrombopoietin signaling. Cell-type and cause-specific approaches will assist the search for future IS and ICH biomarkers and treatments.

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

“…Neutrophils produce a variety of proinflammatory cytokines that affect BBB function, including IL‐1β, TNF‐α, IL‐6, IL‐12, and IFN‐γ, whereas TNF‐α can further induce the recruitment of neutrophils to the CNS. 144‐146 Additionally, when neutrophils transmigrate into the CNS, they secret IL‐1 and activate the antigen‐presenting cells (APC) locally, which subsequently activate endothelial IL‐1R1 signaling that induces T cell recruitment and exacerbates CNS inflammation 147 . Monocytes may migrate across the BBB depending on the upregulation of cytokines (IL‐1) and junction molecules (ALCAM, JAM‐A, PECAM‐1, and CD99) 148,149 .…”

Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: bioinformatics and in vivo and vitro experiments

“…We used CatS −/− mice to clarify the phagosome process in a carotid ligation model. In their article on cerebrovascular accident, Carmona-Mora et al (2021) pointed out that monocytes and neutrophils are the main types of reactive cells. As the most important phagosome-related cells in the human body, neutrophils and monocytes may be closely related to vascular injury and repair.…”

Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression

“…Oxidative stress generally occurs in the excessive ROS generation and/or the deficiency of the antioxidant defence system, that is, the imbalance between the oxidation system and the antioxidant system [ 33 ]. After ischemic stroke, ischemia and hypoxia lead to ATP depletion and mitochondrial dysfunction, resulting in a large number of ROS production [ 34 ]. At the same time, protein synthesis is blocked, which leads to a decrease in antioxidant enzyme production and then the increase of ROS production.…”