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Peripheral blood gene expression in ischemic stroke

Ashley B Petrone, Valerie Gionis, Richard Giersch, Taura L Barr
BACKGROUND: In 2010, there were approximately 2.2 million emergency room visits associated with traumatic brain injury (TBI), with 80 percent diagnosed as mild TBI or concussion. In addition, there are a large number of TBIs, especially mild TBIs, which go either unreported by patients or initially undiagnosed by clinicians. Our team has previously identified a panel of immune-related genes that can diagnose ischemic stroke at triage, and due to shared pathophysiological mechanisms of TBI and stroke, we hypothesized that this panel of genes may also be utilized for the diagnosis of TBI...
February 10, 2017: NeuroRehabilitation
Cheryl Dykstra-Aiello, Glen C Jickling, Bradley P Ander, Natasha Shroff, Xinhua Zhan, DaZhi Liu, Heather Hull, Miles Orantia, Boryana S Stamova, Frank R Sharp
BACKGROUND AND PURPOSE: Although peripheral blood mRNA and micro-RNA change after ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes after stroke. METHODS: lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from patients with ischemic stroke and matched with vascular risk factor controls...
December 2016: Stroke; a Journal of Cerebral Circulation
Weiying Xie, Lili Fang, Shuyuan Gan, Haojun Xuan
Stroke causes brain injury with neuroinflammation which exacerbates the neuronal damage. Recent studies show that anti-inflammatory cytokine interleukin-19 (IL-19) plays a critical part in the inflammatory and ischemic vascular diseases, yet its potential role in ischemic stroke is unknown. Here, we tested the hypothesis that IL-19 exerts protective effects against brain ischemia by modulating inflammation after stroke. Mice were injected intraperitoneally with 10ng/g per day recombinant mouse IL-19 starting pre-stroke, and were subjected to transient middle cerebral artery occlusion...
November 1, 2016: Brain Research
Xin Guo, Lijin Yu, Min Chen, Tian Wu, Xiangdong Peng, Ren Guo, Bikui Zhang
BACKGROUND: Aspirin (ASA) is the most widely used medicine to prevent cardiovascular diseases; however, the mechanisms by which ASA exerts its anti-proliferative effect remain not fully understood. This study was designed to investigate whether miR-145 is involved in the regulation of vascular smooth muscle cells' (VSMCs) proliferation and to determine the anti-inflammatory effects of ASA via its regulation of CD40 to provide a new theoretical basis for the pharmacological effect of aspirin...
2016: Journal of Translational Medicine
Yingying Wang, Yunpeng Cai
Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages...
2016: Scientific Reports
Robert Meller, Andrea N Pearson, Jimmaline J Hardy, Casey L Hall, Dawn McGuire, Michael R Frankel, Roger P Simon
OBJECTIVE: Molecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray-based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next-generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip...
February 2016: Annals of Clinical and Translational Neurology
Lian Gu, Yanli Wu, Shuyan Hu, Qing Chen, Jinjing Tan, Yan Yan, Baoyun Liang, Nong Tang
BACKGROUND: Mitogen-activated protein kinase kinase 4 (MAP2K4) gene acts as the direct upstream activator of c-Jun NH2-terminal kinase pathway, which plays an important role in regulating neuron survival and apoptosis in response to cerebral ischemia. However, the association between MAP2K4 gene polymorphisms and ischemic stroke (IS) has not yet been published. Therefore, this study investigates the association between MAP2K4 gene polymorphism rs3826392 and IS susceptibility, as well as its quantitative traits in Southern Chinese Han population...
May 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Kripa Raman, Martin J O'Donnell, Anna Czlonkowska, Yan Carlos Duarte, Patricio Lopez-Jaramillo, Ernesto Peñaherrera, Mike Sharma, Ashkan Shoamanesh, Marta Skowronska, Salim Yusuf, Guillaume Paré
BACKGROUND AND PURPOSE: A limitation when making early decisions on stroke management is the lack of rapid diagnostic and prognostic testing. Our study sought to identify peripheral blood RNA biomarkers associated with stroke. The secondary aims were to assess the discriminative capacity of RNA biomarkers for primary stroke type and stroke prognosis at 1-month. METHODS: Whole-blood gene expression profiling was conducted on the discovery cohort: 129 first-time stroke cases that had blood sampling within 5 days of symptom onset and 170 control participants with no history of stroke...
March 2016: Stroke; a Journal of Cerebral Circulation
Taura L Barr, Reyna VanGilder, Stephanie Rellick, Steven D Brooks, Danielle N Doll, Ann Noelle Lucke-Wold, Dongquan Chen, James Denvir, Steven Warach, Andrew Singleton, Mar Matarin
OBJECTIVES: The objectives of this study were to determine the change in gene expression between two time points following stroke and to identify biomarkers of stroke recovery through gene expression profiling and pathway analysis. METHODS: Peripheral blood was collected from 34 ischemic stroke patients (confirmed by magnetic resonance imaging) ≥18 years of age, within 24 hr of symptom onset and 24-48 hr later, and from healthy controls. The Modified Rankin Scale (MRS) was used to determine 30-day recovery...
May 2015: Biological Research for Nursing
Han-Bin Lee, Yoon Kim, Hanna Yoo, Ji-Min Lee, Yu-Kyung Kim, Nam-Keun Kim, Jin-Kyeoung Kim, Seung-Hun Oh
OBJECTIVE: Extracranial- and intracranial atherosclerosis (ECAS and ICAS) have been suggested to have different pathogeneses. Blood genomic profiling may identify their unique molecular signatures. METHODS: Whole gene microarray of peripheral blood was performed in 24 patients with acute ischemic stroke (ECAS, n=12; ICAS, n=12) and 12 healthy controls. Differential gene expression and gene set enrichment analysis (GSEA) were conducted. Plasma resistin levels were compared across independent samples of stroke patients with ECAS (n=39), ICAS (n=20), and small vessel disease (SVD, n=57)...
September 2014: Thrombosis Research
Lidia Garcia-Bonilla, Jamie M Moore, Gianfranco Racchumi, Ping Zhou, Jason M Butler, Costantino Iadecola, Josef Anrather
NO produced by inducible NO synthase (iNOS) contributes to ischemic brain injury, but the cell types expressing iNOS and mediating tissue damage have not been elucidated. To examine the relative contribution of iNOS in resident brain cells and peripheral leukocytes infiltrating the ischemic brain, we used bone marrow (BM) chimeric mice in which the middle cerebral artery was occluded and infarct volume was determined 3 d later. iNOS(-/-) mice engrafted with iNOS(+/+) BM exhibited larger infarcts (44 ± 2 mm(3); n = 13; mean ± SE) compared with autologous transplanted iNOS(-/-) mice (24 ± 3 mm(3); n = 10; p < 0...
September 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Boryana Stamova, Glen C Jickling, Bradley P Ander, Xinhua Zhan, DaZhi Liu, Renee Turner, Carolyn Ho, Jane C Khoury, Cheryl Bushnell, Arthur Pancioli, Edward C Jauch, Joseph P Broderick, Frank R Sharp
AIMS: Epidemiological studies suggest that sex has a role in the pathogenesis of cardioembolic stroke. Since stroke is a vascular disease, identifying sexually dimorphic gene expression changes in blood leukocytes can inform on sex-specific risk factors, response and outcome biology. We aimed to examine the sexually dimorphic immune response following cardioembolic stroke by studying the differential gene expression in peripheral white blood cells. METHODS AND RESULTS: Blood samples from patients with cardioembolic stroke were obtained at ≤3 hours (prior to treatment), 5 hours and 24 hours (after treatment) after stroke onset (n = 23; 69 samples) and compared with vascular risk factor controls without symptomatic vascular diseases (n = 23, 23 samples) (ANCOVA, false discovery rate p≤0...
2014: PloS One
Glen C Jickling, Bradley P Ander, Xinhua Zhan, Dylan Noblett, Boryana Stamova, Dazhi Liu
BACKGROUND: microRNA (miRNA) are important regulators of gene expression. In patients with ischemic stroke we have previously shown that differences in immune cell gene expression are present. In this study we sought to determine the miRNA that are differentially expressed in peripheral blood cells of patients with acute ischemic stroke and thus may regulate immune cell gene expression. METHODS: miRNA from peripheral blood cells of forty-eight patients with ischemic stroke and vascular risk factor controls were compared...
2014: PloS One
Eunhee Kim, Aaron T Tolhurst, Sunghee Cho
BACKGROUND: Although elicited inflammation contributes to tissue injury, a certain level of inflammation is necessary for subsequent tissue repair/remodeling. Diabetes, a chronic low-grade inflammatory state, is a predisposing risk factor for stroke. The condition is associated with delayed wound healing, presumably due to disrupted inflammatory responses. With inclusion of the diabetic condition in an experimental animal model of stroke, this study investigates whether the condition alters inflammatory response and influences stroke-induced brain injury...
2014: Journal of Neuroinflammation
Guanggang Li, Ruxiang Xu, Yinghua Cao, Xiaodong Xie, Zhendong Zheng
There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls...
December 2014: Inflammation
Mateusz G Adamski, Yan Li, Erin Wagner, Hua Yu, Chloe Seales-Bailey, Helen Durkin, Qing Hao, Steven A Soper, Michael Murphy, Alison E Baird
T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A) production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors...
2014: PloS One
Z-L Zhang, W-C Wu, J-Q Liu, Y-B Yao, M-D Pan, C-B Yang, J-G Wang, X-W Huang, J-Y Lin
BACKGROUND: Prognostic blood biomarkers in the setting of acute ischemic stroke have become increasingly relevant for risk stratification, monitoring disease and response to therapies, developing targets for neuroprotective treatment and as surrogate end points for treatment trials. AIM: We aim to find the feature genes which can accurately detect acute ischemic stroke and perform function analysis of these crucial genes in peripheral blood mononuclear cells. MATERIALS AND METHODS: The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database which includes 20 ischemic stroke patients and 20 controls...
2014: European Review for Medical and Pharmacological Sciences
Z Meng, M Li, Q He, S Jiang, X Zhang, J Xiao, Y Bai
Neuropathologic processes such as cerebral ischemia can enhance neurogenesis. Angiopoietin-1 (Ang1) emerges as a critical regulator of physiological and pathological angiogenesis during embryonic and postnatal life. Although Ang1 could protect peripheral vasculature from vascular leakage following ischemic injury, the role of Ang1 in long-term neurological recovery after ischemic stroke remains elusive. This study aims to examine whether Ang1 overexpression via lentivirus-mediated gene transfer enhances neurovascular remodeling and improves functional outcome in a rat model of focal cerebral ischemia...
May 16, 2014: Neuroscience
Kristen L Zuloaga, Catherine M Davis, Wenri Zhang, Nabil J Alkayed
Stroke risk and outcome are strongly modified by estrogen. In addition to ovaries, estrogen is produced locally in peripheral tissue by the enzyme aromatase, and extragonadal synthesis becomes the major source of estrogen after menopause. Aromatase gene deletion in female mice exacerbates ischemic brain damage after stroke. However, it is not clear which cell type is responsible for this effect, since aromatase is expressed in multiple cell types, including cerebrovascular endothelium. We tested the hypothesis that cerebrovascular aromatase contributes to sex differences in cerebrovascular endothelial function...
April 1, 2014: American Journal of Physiology. Heart and Circulatory Physiology
Cheng-Yi Chang, Yu-Hsiang Kuan, Jian-Ri Li, Wen-Ying Chen, Yen-Chuan Ou, Hung-Chuan Pan, Su-Lan Liao, Shue-Ling Raung, Chen-Jung Chang, Chun-Jung Chen
Cellular inflammatory response plays an important role in ischemic brain injury and anti-inflammatory treatments in stroke are beneficial. Dietary supplementation with docosahexaenoic acid (DHA) shows anti-inflammatory and neuroprotective effects against ischemic stroke. However, its effectiveness and its precise modes of neuroprotective action remain incompletely understood. This study provides evidence of an alternative target for DHA and sheds light on the mechanism of its physiological benefits. We report a global inhibitory effect of 3 consecutive days of DHA preadministration on circulating and intracerebral cellular inflammatory responses in a rat model of permanent cerebral ischemia...
December 2013: Journal of Nutritional Biochemistry
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