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Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage

ABSTRACT: Longitudinal transcriptomic profiling of myeloid cells from cerebral hemorrhage patients reveals conserved features of the inflammatory response and highlights the potential importance of cellular metabolism in guiding macrophage functions and improved patient outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163256 | GEO | 2021/02/19

REPOSITORIES: GEO

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Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage

Project description:Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage

| PRJNA685426 | ENA

Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage.

Project description:Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.

| S-EPMC8252865 | biostudies-literature

Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage [16S rRNA-Seq]

Project description:We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. The relationship between changes in bacterial flora and the prognosis of spontaneous cerebral hemorrhage was studied in two cohort studies. Fecal samples from healthy volunteers and patients with intracerebral hemorrhage were subjected to 16S rRNA sequencing at three time points: T1 (within 24 hours of admission), T2 (3 days post-surgery), and T3 (7 days post-surgery) using Illumina high-throughput sequencing technology.

2024-08-22 | E-MTAB-14351 | biostudies-arrayexpress

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage

Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

2024-06-11 | GSE264394 | GEO

Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu

Project description:Intracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury, particularly over time, in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIEIII) trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-sequencing, we characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution for the first time. Our analysis revealed rapid shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic re-bleed (second local exposure to blood) that our transcriptional data indicated occurred more than 30 hours prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods like scRNA-seq can inform our understanding of complex intracerebral events.

2021-06-02 | GSE166638 | GEO

LH3 overexpression reverses profound alterations of gene transcriptional profile in cerebral vessels in hypertension-induced spontaneous intracerebral hemorrhage

Project description:To gain mechanistic insights into the protection effects of lysyl hydroxylase (LH3) on reducing the susceptibility to intracerebral hemorrhage(ICH), a whole transcriptomic analysis of cerebral vessels were performed using RNA-seq. It is noteworthy that our preliminary data demonstrated that mice did not developed ICH until day 7 after AngII plus L-NAME infusion, cerebral vessels for RNA-seq were acquired at day 5 in order to provide the mechanistic or causal evidence of a direct participatory role of LH3 to the protection effects of ICH.

2018-04-16 | GSE113151 | GEO

Transcriptome sequencing of human brain tissue after intracerebral hemorrhage

Project description:We used tissue bulk RNA-seq to analyze gene expression profile in the brain after intracerebral hemorrhage.

2021-09-01 | GSE167758 | GEO

Analysis of Age-Dependent Transcriptomic Changes in Response to Intracerebral Hemorrhage in Mice

Project description:To investigate age-dependent transcriptomic changes between young or aged intracerebral hemorrhage mice, we established collagenase IV-induced intracerebral hemorrhage mice models. Intracerebral hemorrhage was induced by infusion of sterile collagenase IV in ipsilateral caudate putamen of brain. We then performed gene expression profiling analysis using data obtained from RNA-seq of brain perihematomal tissues from young or aged ICH mice 24 hours after intracerebral hemorrhage.

2022-04-29 | GSE200575 | GEO

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage

Project description:Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage

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Development of gene expression signatures in experimental intracerebral hemorrhage

Project description:To identify the potential lncRNA and mRNA post intracerebral hemorrhage (ICH), we have employed lncRNA microarray expression profiling. 570 mRNAs and 313 lncRNAs were identified in the ICH vs sham group .Expression of six mRNA (Saa3, Col10a1, Mmp13, Oxt, Pcdhb6 and Resp18) and lncRNA (ENSMUT00000141700, AK143011, ENSMUT00000128306, AK030988, ENSMUST00000187076 and ENSMUST00000134129) from this signature was quantified by qPCR.

2023-05-17 | GSE227683 | GEO

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