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Gene expression in peripheral blood in stroke

Kelly M DeMars, Changjun Yang, Kimberly E Hawkins, Austin O McCrea, David M Siwarski, Eduardo Candelario-Jalil
P-glycoprotein (P-gp) is known to transport a diverse array of xenobiotics, including therapeutic drugs. A member of the ATP-binding cassette (ABC) transporter family, P-gp is a protein encoded by the gene Mdr1 in humans and Abcb1 in rodents (represented by 2 isoforms Abcb1a and Abcb1b). Lining the luminal and abluminal membrane of brain capillary endothelial cells, P-gp is a promiscuous efflux pump extruding a variety of exogenous toxins and drugs. In this study, we measured dynamic changes in Abcb1a and Abcb1b transcripts and P-gp protein in the brain, liver, and kidney after experimental stroke...
2017: Journal of Experimental Neuroscience
Grant C O'Connell, Madison B Treadway, Ashley B Petrone, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging...
April 26, 2017: Scientific Reports
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
Adonis Sfera, Carolina Osorio, Luzmin Inderias, Michael Cummings
BACKGROUND: Exposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear...
2016: Frontiers in Endocrinology
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
Mikel Allende, Eva Molina, Elisabet Guruceaga, Ibai Tamayo, José Ramón González-Porras, Tomás José Gonzalez-López, Estefanía Toledo, Obdulia Rabal, Ana Ugarte, Vanesa Roldán, José Rivera, Julen Oyarzabal, Ramón Montes, José Hermida
AIMS: Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapies. METHODS AND RESULTS: Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke brought to light a stroke-related gene expression pattern...
June 1, 2016: Cardiovascular Research
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
L Perisic, S Aldi, Y Sun, L Folkersen, A Razuvaev, J Roy, M Lengquist, S Åkesson, C E Wheelock, L Maegdefessel, A Gabrielsen, J Odeberg, G K Hansson, G Paulsson-Berne, U Hedin
BACKGROUND: Embolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability. METHODS: Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed...
March 2016: Journal of Internal Medicine
Shinichi Asano, Paul D Chantler, Taura L Barr
Biomarker profiling is utilized to identify diagnostic and prognostic candidates for stroke. Clinical and preclinical biomarker data suggest altered circulating immune responses may illuminate the mechanisms of stroke recovery. However, the relationship between peripheral blood biomarker profile(s) and brain profiles following stroke remains elusive. Data show that neutrophil lymphocyte ratio (NLR) predicts stroke outcome. Neutrophils release Arginase 1 (ARG1) resulting in T lymphocyte suppression in peripheral blood...
February 2016: Current Opinion in Pharmacology
Maria Antonietta Isgrò, Patrizia Bottoni, Roberto Scatena
Neuron-specific enolase (NSE) is known to be a cell specific isoenzyme of the glycolytic enzyme enolase. In vertebrate organisms three isozymes of enolase, expressed by different genes, are present: enolase α is ubiquitous; enolase β is muscle-specific and enolase γ is neuron-specific. The expression of NSE, which occurs as γγ- and αγ-dimer, is a late event in neural differentiation, thus making it a useful index of neural maturation.NSE is a highly specific marker for neurons and peripheral neuroendocrine cells...
2015: Advances in Experimental Medicine and Biology
Gregory Konat
It has been well established that peripheral inflammation resulting from microbial infections profoundly alters brain function. This review focuses on experimental systems that model cerebral effects of peripheral viral challenge. The most common models employ the induction of the acute phase response via intraperitoneal injection of a viral mimetic, polyinosinic-polycytidylic acid (PIC). The ensuing transient surge of blood-borne inflammatory mediators induces a "mirror" inflammatory response in the brain characterized by the upregulated expression of a plethora of genes encoding cytokines, chemokines and other inflammatory/stress proteins...
February 2016: Neurochemical Research
R D Spescha, J Klohs, A Semerano, G Giacalone, R S Derungs, M F Reiner, D Rodriguez Gutierrez, N Mendez-Carmona, M Glanzmann, G Savarese, N Kränkel, A Akhmedov, S Keller, P Mocharla, M R Kaufmann, R H Wenger, J Vogel, L Kulic, R M Nitsch, J H Beer, L Peruzzotti-Jametti, M Sessa, T F Lüscher, G G Camici
AIM: Constitutive genetic deletion of the adaptor protein p66(Shc) was shown to protect from ischaemia/reperfusion injury. Here, we aimed at understanding the molecular mechanisms underlying this effect in stroke and studied p66(Shc) gene regulation in human ischaemic stroke. METHODS AND RESULTS: Ischaemia/reperfusion brain injury was induced by performing a transient middle cerebral artery occlusion surgery on wild-type mice. After the ischaemic episode and upon reperfusion, small interfering RNA targeting p66(Shc) was injected intravenously...
July 1, 2015: European Heart Journal
Goknur Haliloglu, Jérome Maluenda, Bahattin Sayinbatur, Cedric Aumont, Cagri Temucin, Betul Tavil, Mualla Cetin, Kader K Oguz, Ivo Gut, Veronique Picard, Judith Melki, Haluk Topaloglu
OBJECTIVE: To identify the underlying etiology of 3 patients in a multiplex family with strokes, chronic immune-mediated peripheral neuropathy, and hemolysis. All had onset in infancy. METHODS: We performed genome-wide linkage analysis followed by whole exome sequencing (WES) in the proband, Sanger sequencing, and segregation analysis of putative mutations. In addition, we conducted flow cytometry studies to assess CD59 expression. RESULTS: In a 2-generation-3-affected family with early-onset immune-mediated axonal neuropathy, cerebrovascular event both in the anterior and posterior circulation, and chronic Coombs-negative hemolysis, we detected CD59 deleterious mutation as the underlying cause...
March 24, 2015: Neurology
Azhar Abbas, Ida Gregersen, Sverre Holm, Isabelle Daissormont, Vigdis Bjerkeli, Kirsten Krohg-Sørensen, Karolina R Skagen, Tuva B Dahl, David Russell, Trine Almås, Dorte Bundgaard, Lars Holger Alteheld, Azita Rashidi, Christen P Dahl, Annika E Michelsen, Erik A Biessen, Pål Aukrust, Bente Halvorsen, Mona Skjelland
BACKGROUND AND PURPOSE: Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis. METHODS: Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells...
March 2015: Stroke; a Journal of Cerebral Circulation
Magdalena Justyna Kacperska, Karol Jastrzebski, Bartlomiej Tomasik, Jakub Walenczak, Maria Konarska-Krol, Andrzej Glabinski
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90% of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression...
May 2015: Journal of Molecular Neuroscience: MN
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