scholarly journals The intracerebral hemorrhage blood transcriptome in humans differs from the ischemic stroke and vascular risk factor control blood transcriptomes

2018 ◽  
Vol 39 (9) ◽  
pp. 1818-1835 ◽  
Author(s):  
Boryana Stamova ◽  
Bradley P Ander ◽  
Glen Jickling ◽  
Farah Hamade ◽  
Marc Durocher ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Vascular Risk Factor ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
T Helper ◽  
Self Organizing Maps ◽  
Treatment And Prevention ◽  
Mixed Regression ◽  
Blood Transcriptome

Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected p(Dx) < 0.2 and p < 0.005 and |FC| > 1.2 for individual comparisons. For time-dependent analyses, subjects were divided into four time-points: 0(CTRL), <24 h, 24–48 h, >48 h; 489 transcripts were differentially expressed between ICH and CTRL, and 63 between IS and CTRL. ICH had differentially expressed T-cell receptor and CD36 genes, and iNOS, TLR, macrophage, and T-helper pathways. IS had more non-coding RNA. ICH and IS both had angiogenesis, CTLA4 in T lymphocytes, CD28 in T helper cells, NFAT regulation of immune response, and glucocorticoid receptor signaling pathways. Self-organizing maps revealed 4357 transcripts changing expression over time in ICH, and 1136 in IS. Understanding ICH and IS transcriptomes will be useful for biomarker development, treatment and prevention strategies, and for evaluating how well animal models recapitulate human ICH and IS.

scholarly journals Screening for differentially expressed circRNAs in ischemic stroke by RNA sequencing

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Duncan Wei ◽  
Jian Chen ◽  
Xiaopu Chen ◽  
Shaoyan Wu ◽  
Zhaolin Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Signaling ◽  
Qrt Pcr ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling ◽  
Host Genes

Abstract Background Ischemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke. Methods RNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Results A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. Conclusions The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

Abstract WP416: Specific Transcriptome Response in Neutrophils, Monocytes and Whole Blood in Human Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Paulina Carmona-Mora ◽  
Bradley P Ander ◽  
Glen C Jickling ◽  
Xinhua Zhan ◽  
Farah Hamade ◽  
...  
Keyword(s):  
Immune Response ◽  
Ischemic Stroke ◽  
Blood Cell ◽  
Intracerebral Hemorrhage ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Receptor Gene ◽  
Cell Types ◽  
Cell Receptor ◽  
Transcriptional Responses

Understanding transcriptome changes following intracerebral hemorrhage (ICH) and ischemic stroke (IS) of different etiologies, can lead to a better understanding of the molecular and cellular pathways involved in the response to acute brain injury caused by ICH and IS. We characterized the transcriptomic profiles from ICH and different IS etiologies to identify acute molecular changes in isolated monocytes, neutrophils and in whole blood. Peripheral blood was drawn from ICH (6) and IS (33) cases (cardioembolic, large vessel and lacunar) in the first 30 ± 20 hours post-onset of symptoms. We performed whole-genome RNA sequencing of whole blood (WB), and isolated neutrophils and monocytes. Control cases (10) with vascular risk factors (diabetes and/or hypertension and/or hypercholesterolemia) were also included (VRFC). A linear regression model including the interaction diagnosis x sample subtype with p<0.05 and overlap with FDR<0.2, (fold-change>1.2) was used for identifying differentially expressed (DE) genes. Gene ontology and pathway enrichment were performed for investigating the biological context of the DE. We observed specific transcriptional responses for ICH and IS, and within IS etiologies in monocytes, neutrophils and WB. Neutrophils’ response was the strongest with highest number of DE genes in both ICH and IS and its etiologies when compared to VRFC. Most of the changes were cell-type specific and involved immune response and signal transduction pathways. For example, in ICH compared to VRFC, about half of the over-represented pathways were unique to either monocytes or neutrophils. Many pathways over-represented in WB were not over-represented in monocytes or neutrophils, signifying the importance of additional blood cell types in the immune response to ICH and IS. A T-cell receptor gene was DE in WB only, and in opposite directions in ICH and IS when compared to VRFC, thus is a good biomarker candidate. The unique expression changes in neutrophils and monocytes after ICH and IS and its subtypes underscore their involvement in IS and ICH pathophysiology. The large number of unique genes and pathways in whole blood not detected in monocytes or neutrophils signify the contribution of other peripheral blood cell types to the ICH and IS responses.

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

2020 ◽  
pp. 0271678X2095391
Author(s):  
Paulina Carmona-Mora ◽  
Bradley P Ander ◽  
Glen C Jickling ◽  
Cheryl Dykstra-Aiello ◽  
Xinhua Zhan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Nk Cell ◽  
Death Receptor ◽  
Vascular Risk Factor ◽  
Peripheral Blood Monocyte ◽  
Dendritic Cell Maturation ◽  
Growth Factor Signaling ◽  
Rna Seq ◽  
Death Receptor Signaling

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.

Factor V Leiden Mutation in Cerebrovascular Disease

2005 ◽  
Vol 11 (3) ◽  
pp. 339-342 ◽  
Author(s):  
Nur Buyru ◽  
Julide Altinisik ◽  
Goksel Somay ◽  
Turgut Ulutin
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Cerebrovascular Disease ◽  
Smoking Status ◽  
Factor V Leiden ◽  
Restriction Enzyme Digestion ◽  
Factor V ◽  
Mutation Site ◽  
Factor V Leiden Mutation ◽  
High Prevalence

Several studies indicate a high prevalence of factor V Leiden mutation as the most frequent coagulation defect found in patients with venous thrombosis. The relationship between this mutation and cerebrovascular disease has not been established in adults. In this investigation, we studied 29 patients with ischemic stroke and 20 with intracerebral hemorrhage, all of whom were compared with 20 controls. A region of the factor V gene containing the Leiden mutation site was amplified with polymerase chain reaction and the presence of mutation was determined with restriction enzyme digestion. We found no evidence of an association between factor V Leiden mutation and ischemic stroke or intracerebral hemorrhage. There was no evidence of association in subgroup the analysis by age, smoking status, myocardial infarction, hypertension, diabetes mellitus, or coronary disease. Factor V Leiden mutation doesn’t seem to be associated with a risk of cerebrovascular disease.

scholarly journals Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

1999 ◽  
Vol 190 (5) ◽  
pp. 607-616 ◽  
Author(s):  
Hideki Iijima ◽  
Ichiro Takahashi ◽  
Daisuke Kishi ◽  
Jin-Kyung Kim ◽  
Sunao Kawano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Bowel Disease ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
T Helper ◽  
Inflammatory Bowel ◽  
Α Chain

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4+TCR-ββ (CD4+ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4+ββ T cells, we treated TCR-α−/− mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-α−/− mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-α−/− mice treated with either specific or mock Ab developed CD4+ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon γ–specific expression. These findings suggest that IL-4–producing Th2-type CD4+ββ T cells play a major immunopathological role in the induction of IBD in TCR-α−/− mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4+ββ T cells to shift to the Th1 type.

scholarly journals Activating NK cell receptor ligands are differentially expressed during progression to cervical cancer

2008 ◽  
Vol 123 (10) ◽  
pp. 2343-2353 ◽  
Author(s):  
Sonja Textor ◽  
Matthias Dürst ◽  
Lars Jansen ◽  
Rosita Accardi ◽  
Massimo Tommasino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Nk Cell ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Ligands ◽  
Nk Cell Receptor
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