scholarly journals Aging Immune System in Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1355-1361
Author(s):  
Gina P. Sykes ◽  
Joseph Kamtchum-Tatuene ◽  
Sarina Falcione ◽  
Sarah Zehnder ◽  
Danielle Munsterman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Stroke ◽  
Immune System ◽  
Acute Ischemic Stroke ◽  
Stroke Risk ◽  
Cell Receptor ◽  
Derivation Cohort ◽  
Humoral Immune ◽  
Age Related ◽  
Whole Genome Microarray

Background and Purpose: With advancing age, alterations occur to the immune system, including an increase in inflammation (inflammaging) and a reduced ability to respond to new immune challenges. The role of an aging immune system in patients with ischemic stroke remains unclear, although age is an important determinant of stroke risk and outcome. This study assessed the aging immune system in patients with acute ischemic stroke by differences in leukocyte gene expression in relationship to age. Methods: Peripheral blood RNA from 2 cohorts with acute ischemic stroke was measured by whole-genome microarray, and genes associated with advancing age were identified (false discovery rate-corrected P <0.05, partial correlation coefficient <|0.3|). Genes were characterized by pathway analysis and compared with age-associated genes from nonstroke studies (n=3974). Results: There were 166 genes associated with age in cohort 1 (derivation cohort, n=94). Sixty-nine of these age-associated genes were verified in cohort 2 (validation cohort, n=79). Identified genes included a decrease in CR2 , CD27 , CCR7 , and NT5E . Genes were associated with altered B-cell receptor signaling, lymphocyte proliferation, and leukocyte homeostasis. Forty-three of the 69 age-associated genes in stroke were also associated with age in nonstroke studies. Conclusions: A relationship between leukocyte gene expression and age in patients with ischemic stroke was identified. The changes include alterations to the adaptive humoral immune system, which may influence age-related stroke risk and outcome.

Abstract P646: The Aging Immune Transcriptome is Linked to Ischemic Stroke Outcome

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Gina P Sykes ◽  
Sarina Falcione ◽  
Joseph Kamtchum Tatuene ◽  
Boryana Stamova ◽  
Bradley Ander ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Stroke ◽  
Immune System ◽  
Lymphocyte Activation ◽  
Enrichment Analysis ◽  
Stroke Outcome ◽  
Humoral Immune ◽  
Age Related ◽  
Humoral Immune System ◽  
The Relationship

Background: Advancing age is associated with changes to the immune system, which affect stroke outcome. We previously demonstrated an age-associated alteration in leukocyte gene expression in patients with ischemic stroke. The aim of this study is to validate these findings in an independent stroke cohort and assess the relationship to stroke outcome. Methods: Genes associated with age were identified in a cohort of 57 patients with acute ischemic stroke. Peripheral blood RNA was measured using whole genome microarrays and genes associated with advancing age identified (FDR-corrected p < 0.05, partial correlation coefficient r > |0.3|); age-associated gene expression differences in patients with poor 90-day outcome (mRS < 2) were also compared. Genes were functionally characterized by pathway and enrichment analysis and verified against age-associated genes from two additional stroke cohorts containing a total of 173 patients. Results: There were 536 genes associated with age in the new stroke cohort, of which 286 decreased and 253 increased with age. Thirty-nine (39) of the age-associated genes were present in previous stroke cohorts analyzed, including a decrease in CCR6, CXCR5, BLNK and NT5E. A decrease in CXCR5 and CD79B was also identified in patients with poor outcome. Pathways and enriched terms relating to the humoral adaptive system immune system, including B-cell and lymphocyte activation, were among those represented in age-associated genes. Conclusions: Age-related changes in leukocyte gene expression were validated in an independent cohort of patients with ischemic stroke. Verified changes include alterations to the humoral immune system and a relationship to stroke outcome. Further investigation of the aging immune system in stroke is warranted.

Abstract TP166: Age-Associated Transcriptomic Alterations in Patients With Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Gina Sykes ◽  
Yusra Batool ◽  
Joseph Kamtchum Tatuene ◽  
Sarah Zehnder ◽  
Glen C Jickling
Keyword(s):  
Gene Expression ◽  
Functional Analysis ◽  
Ischemic Stroke ◽  
Immune System ◽  
B Cell ◽  
Differentially Expressed Genes ◽  
Hemorrhagic Transformation ◽  
Differentially Expressed ◽  
P Value ◽  
Humoral Immune

Introduction: Immune system dysregulation occurs with age. This includes an increase in inflammation, and immunosenescence, the inability to efficiently respond to new immune challenges. These changes are evident in various diseases but have yet to be evaluated in a population with ischemic stroke. Age is an important factor in stroke, contributing to stroke risk, outcome and risk of hemorrhagic transformation. This study aimed to assess the changes that occur with age in the leukocyte gene expression of patients with ischemic stroke. Methods: Two cohorts of acute ischemic stroke patients were analyzed; cohort 1 (n=94) and cohort 2 (n=79). RNA was isolated from PAXgene tubes and processed on Affymetrix microarrays. Differentially expressed genes associated with age quartiles were identified by ANCOVA, adjusted for sex and batch. Functional analysis identified age-associated pathways. Differentially expressed genes were compared with previous non-stroke aging studies in whole blood. Results: There were 61 and 442 age-associated genes in cohorts 1 and 2 respectively (FDR-corrected p<0.05, partial correlation coefficient ≥ |0.3|). Nineteen genes, including CR2, CCR6 and CXCR5 , were found in common and decreased with age among both cohorts (max-log10(p value) = 17). Functional analysis of the 61 and 442 genes revealed with advancing age there is a change in the humoral immune system, including antibody production and B cell proliferation. When compared to aging gene expression studies in controls, 52% of age-associated genes in cohort 1 and 31% of cohort 2 age-associated genes overlapped with those found in controls, and 16 of the 19 common genes to both cohorts overlapped in controls (max-log10(p value) = 15). Conclusion: In patients with acute stroke there is a change in leukocyte gene expression with advancing age. Changes included a shift in humoral immune response with a potentially impaired B cell response. While many of the age-associated alterations in gene expression present in stroke are similar to non-stroke controls, these changes warrant further investigation for their impact on stroke outcome and risk.

Abstract WP182: Trends in Acute Ischemic Stroke Hospitalizations and Risk Factors Among Young Adults: 12 Years of Nationally Representative Data

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Urvish K Patel ◽  
Priti Poojary ◽  
Vishal Jani ◽  
Mandip S Dhamoon
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Young Adults ◽  
Ischemic Stroke ◽  
Length Of Stay ◽  
Acute Ischemic Stroke ◽  
Stroke Risk ◽  
Behavioral Risk Factors ◽  
Behavioral Risk ◽  
Stroke Risk Factors

Background: There is limited recent population-based data of trends in acute ischemic stroke (AIS) hospitalization rates among young adults (YA). Rising prevalence of stroke risk factors may increase stroke rates in YA. We hypothesized that 1) stroke hospitalizations and mortality among YA are increasing over time (2000-2011), 2) besides traditional stroke risk factors, non-traditional factors are associated with stroke in YA, 3) stroke hospitalization among YA is associated with higher mortality, length of stay (LOS), and cost. Methods: In the Nationwide Inpatient Sample database (years 2000-2011), adult hospitalizations for AIS and concurrent diagnoses were identified by ICD-9-CM codes; the analytic cohort constituted all AIS hospitalizations. We performed weighted analysis using chi-square, t-test, and Jonckheere trend test. Multivariable survey regression models evaluated interactions between age group (18-45 vs. >45 years) and traditional and non-traditional risk factors, with outcomes including mortality, LOS, and cost. Models were adjusted for race, sex, Charlson’s Comorbidity Index, primary payer, location and teaching status of hospital, and admission day. Results: Among 5220960 AIS hospitalizations, 231858 (4.4%) were YA. On trend analysis, proportion of YA amongst AIS increased from 3.6% in 2000 to 4.7% in 2011 (p<0.0001) but mortality in YA decreased from 3.7% in 2000 to 2.6% in 2011, compared to 7.1% in 2000 to 4.6% in 2011 (p<0.0001) among older adults. Non-traditional, especially behavioral, risk factors were more common among YA, and LOS and cost were higher (Table). Conclusion: There was a trend for higher proportion of YA among AIS hospitalizations, though there was a decreasing mortality trend over 10 years. Behavioral risk factors were more common among YA, and there was an increased length of stay and cost. AIS in YA may require different preventive approaches compared to AIS among older adults.

Abstract TMP57: The Influence of Telomere Length on Ischemic Stroke Risk and Phenotype

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ezgi Yetim ◽  
Mehmet A Topcuoglu ◽  
Nuket Yurur Kutlay ◽  
Ajlan Tukun ◽  
Kader K Oguz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Telomere Length ◽  
Significant Relationship ◽  
Stroke Risk ◽  
Prior History ◽  
Lesion Volume ◽  
Nihss Score ◽  
Stroke Etiology ◽  
Age Related

Background: Telomeres are specific nucleotide repeats that play a central role in control of DNA damage related to cell division and aging. The degree of telomere shortening that occurs as part of aging is associated with age-related non-cancer diseases like hypertension, diabetes mellitus and coronary artery disease. Although a number of studies have highlighted that a similar relationship might exist with ischemic stroke, contradictory reports are also present in the literature. In this study we investigated the association between telomere length and ischemic stroke, not only in terms of stroke risk in general, but also from the perspective of stroke etiology and severity. Methods: In a Caucasian cohort, telomere length was determined by Southern blot from peripheral blood leukocytes in 163 consecutive ischemic stroke patients, and 210 controls without any prior history of ischemic stroke. Univariate and multivariate analyses were performed to determine the contribution of telomere length to stroke risk, stroke etiology, admission NIHSS score and DWI lesion volume. Results: The median (interquartile range) telomere length was 7.0 (5.5-9.0) kb in the overall population. Expectedly, telomere length was negatively correlated with aging (r=-0.23; p<0.001). A short telomere length (i.e. lowest quartile; ≤5.5 kb) was significantly associated with ischemic stroke (OR 3.0, 95%CI 1.8-5.1) when adjusted for age, gender and cardiovascular risk factors. This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. There was no significant relationship between admission lesion volume and telomere length; however, patients with short telomeres presented with more severe strokes (NIHSS score ≥16) when adjusted for age, risk factors, stroke etiology and infarct volume (OR 7.0; 95%CI 1.7-28.7). Conclusion: Almost all etiologic subtypes of ischemic stroke are related to shortened telomere length, irrespective of the age of the subject. Furthermore, presence of short telomeres negatively influences the tolerance of brain to ischemia, thereby causing more severe clinical phenotypes in these patients in the setting of ischemic stroke.

Abstract TP215: Machine Learning Analysis of Gene Expression Data and Predictive Stroke Outcomes in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sarah R Martha ◽  
Qiang Cheng ◽  
Liyu Gong ◽  
Lisa Collier ◽  
Stephanie Davis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Stroke Patients ◽  
Stroke Outcomes ◽  
Inflammatory Genes ◽  
Patient Demographics ◽  
Edema Volume

Background and Purpose: The ability to predict ischemic stroke outcomes in the first day of admission could be vital for patient counseling, rehabilitation, and care planning. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) collects blood samples distal and proximal to the intracranial thrombus during mechanical thrombectomy. These samples are a novel resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and patient demographics that are predictive of stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients. Methods: The BACTRAC study is a non-probability, convenience sampling of subjects (≥ 18 year olds) treated with mechanical thrombectomy for emergent large vessel occlusion. We evaluated relative concentrations of mRNA for gene expression in 84 inflammatory molecules in static blood distal and proximal to the intracranial thrombus from adults who underwent thrombectomy. We employed a machine learning method, Random Forest, utilizing the first set of enrolled subjects, to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. Results: We analyzed the first 28 subjects (age = 66 ± 15.48, 11 males) in the BACTRAC registry. Results from machine learning analyses demonstrate that the genes CCR4, IFNA2, IL9, CXCL3, Age, DM, IL7, CCL4, BMI, IL5, CCR3, TNF, and IL27 predict infarct volume. The genes IFNA2, IL5, CCL11, IL17C, CCR4, IL9, IL7, CCR3, IL27, DM, and CSF2 predict edema volume. There is an intersection of genes CCR4, IFNA2, IL9, IL7, IL5, CCR3 to both infarct and edema volumes. Overall, these genes depicts a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils. Conclusions: Machine learning algorithms can be employed to develop predictive biomarker signatures for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.

scholarly journals Age-related DNA hydroxymethylation is enriched for gene expression and immune system processes in human peripheral blood

Epigenetics ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 294-306 ◽  
Author(s):  
Nicholas D. Johnson ◽  
Luoxiu Huang ◽  
Ronghua Li ◽  
Yun Li ◽  
Yuchen Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Dna Hydroxymethylation ◽  
Age Related

scholarly journals Microarray analysis of aging-associated immune system alterations in the rostral ventrolateral medulla of F344 rats

2017 ◽  
Vol 49 (8) ◽  
pp. 400-415 ◽  
Author(s):  
Sivasai Balivada ◽  
Chanran K. Ganta ◽  
Yongqing Zhang ◽  
Hitesh N. Pawar ◽  
Richard J. Ortiz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Neural Substrates ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Middle Aged ◽  
Transcriptomic Profile ◽  
Age Related ◽  
F344 Rats ◽  
Age Related Changes

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats were analyzed with Agilent’s whole rat genome microarray. The RVLM gene expression profile varied with age, and an association between chronological age and specific RVLM gene expression patterns was observed [ P < 0.05, false discovery rate (FDR) < 0.3]. Functional analysis of RVLM microarray data via gene ontology profiling and pathway analysis identified upregulation of genes associated with immune- and stress-related responses and downregulation of genes associated with lipid biosynthesis and neurotransmission in aged compared with middle-aged and young rats. Differentially expressed genes associated with the complement system and microglial cells were further validated by quantitative PCR with separate RVLM samples ( P < 0.05, FDR < 0.1). The present results have identified age-related changes in the transcriptomic profile of the RVLM, modifications that may provide the molecular backdrop for understanding age-dependent changes in physiological regulation.

scholarly journals Age-related metabolic disturbances in adult patients with acute ischemic stroke

2015 ◽  
Vol 47 (3) ◽  
pp. 48
Author(s):  
Daniela Yordanova Arabadzhieva ◽  
Zdravko Slavov ◽  
Vesela Zlateva ◽  
Ara Kapreelyan
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Adult Patients ◽  
Metabolic Disturbances ◽  
Age Related

scholarly journals Neuronal and Glia-Related Biomarkers in Cerebrospinal Fluid of Patients with Acute Ischemic Stroke

2014 ◽  
Vol 6 ◽  
pp. JCNSD.S13821 ◽  
Author(s):  
Clara Hjalmarsson ◽  
Maria Bjerke ◽  
Björn Andersson ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Experimental Studies ◽  
Csf Biomarkers ◽  
Stroke Severity ◽  
Neurofilament Light ◽  
Age Related ◽  
T Tau

Background Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). Methods A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. Results Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). Conclusions Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

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