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.

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 Intracerebral Hemorrhage and Ischemic Stroke of Different Etiologies Have Distinct Alternatively Spliced mRNA Profiles in the Blood: a Pilot RNA-seq Study

2015 ◽  
Vol 6 (4) ◽  
pp. 284-289 ◽  
Author(s):  
Cheryl Dykstra-Aiello ◽  
Glen C. Jickling ◽  
Bradley P. Ander ◽  
Xinhua Zhan ◽  
DaZhi Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Rna Seq ◽  
Alternatively Spliced

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 Predicting the Risk of Symptomatic Intracerebral Hemorrhage in Ischemic Stroke Treated With Intravenous Alteplase

Stroke ◽  
2012 ◽  
Vol 43 (6) ◽  
pp. 1524-1531 ◽  
Author(s):  
Michael Mazya ◽  
José A. Egido ◽  
Gary A. Ford ◽  
Kennedy R. Lees ◽  
Robert Mikulik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Intravenous Alteplase

Beyond apoptosis: nonapoptotic cell death in physiology and disease

2005 ◽  
Vol 83 (5) ◽  
pp. 579-588 ◽  
Author(s):  
Claudio A Hetz ◽  
Vicente Torres ◽  
Andrew F.G Quest
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Death Receptor ◽  
Receptor Signaling ◽  
Family Analysis ◽  
Caspase Family ◽  
Death Receptor Signaling ◽  
Apoptotic Pathways ◽  
Nonapoptotic Cell Death ◽  
High Degree

Apoptosis is a morphologically defined form of programmed cell death (PCD) that is mediated by the activation of members of the caspase family. Analysis of death-receptor signaling in lymphocytes has revealed that caspase-dependent signaling pathways are also linked to cell death by nonapoptotic mechanisms, indicating that apoptosis is not the only form of PCD. Under physiological and pathological conditions, cells demonstrate a high degree of flexibility in cell-death responses, as is reflected in the existence of a variety of mechanisms, including necrosis-like PCD, autophagy (or type II PCD), and accidental necrosis. In this review, we discuss recent data suggesting that canonical apoptotic pathways, including death-receptor signaling, control caspase-dependent and -independent cell-death pathways.Key words: apoptosis, necrosis, nonapoptotic programmed cell death, death receptors, ceramides.

scholarly journals Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuejiao Li ◽  
Yankai Dong ◽  
Ye Ran ◽  
Yanan Zhang ◽  
Boyao Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Proinflammatory Cytokines ◽  
Infarct Volume ◽  
Brain Lesion ◽  
Three Dimensional ◽  
Artery Occlusion ◽  
Rna Seq ◽  
The Brain

Abstract Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.

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