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Gene expression profile in early ischemic stroke

Wei-Na Jin, Andrew F Ducruet, Qiang Liu, Samuel Xiang-Yu Shi, Michael Waters, Ming Zou, Kevin N Sheth, Rayna Gonzales, Fu-Dong Shi
Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ...
May 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
TaeHo Kong, Ji-Min Park, Ji Hyon Jang, C-Yoon Kim, Sang-Hun Bae, Yuri Choi, Yun-Hwa Jeong, Chul Kim, Sung Woon Chang, Joopyung Kim, Jisook Moon
Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs...
January 12, 2018: Experimental & Molecular Medicine
Whitney S Gibbs, Rachel A Weber, Rick G Schnellmann, DeAnna L Adkins
AIMS: Determine the subacute time course of mitochondria disruption, cell death, and inflammation in a rat model of unilateral motor cortical ischemic stroke. MAIN METHODS: Rats received unilateral ischemia of the motor cortex and were tested on behavioral tasks to determine impairments. Animals were euthanized at 24h, 72h and 144h and mRNA expression of key mitochondria proteins and indicators of inflammation, apoptosis and potential regenerative processes in ipsilesion cortex and striatum, using RT-qPCR...
December 1, 2016: Life Sciences
Vinh A Nguyen, Leeanne M Carey, Loretta Giummarra, Pierre Faou, Ira Cooke, David W Howells, Tamara Tse, S Lance Macaulay, Henry Ma, Stephen M Davis, Geoffrey A Donnan, Sheila G Crewther
Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis...
2016: Frontiers in Neurology
Raffaella Moretti, Pierre-Louis Leger, Valérie C Besson, Zsolt Csaba, Julien Pansiot, Lorena Di Criscio, Andrea Gentili, Luigi Titomanlio, Philippe Bonnin, Olivier Baud, Christiane Charriaut-Marlangue
BACKGROUND: Perinatal ischemic stroke is the most frequent form of cerebral infarction in neonates; however, evidence-based treatments are currently lacking. We have previously demonstrated a beneficial effect of sildenafil citrate, a PDE-5 inhibitor, on stroke lesion size in neonatal rat pups. The present study investigated the effects of sildenafil in a neonatal mouse stroke model on (1) hemodynamic changes and (2) regulation of astrocyte/microglia-mediated neuroinflammation. METHODS: Ischemia was induced in C57Bl/6 mice on postnatal (P) day 9 by permanent middle cerebral artery occlusion (pMCAo), and followed by either PBS or sildenafil intraperitoneal (i...
April 28, 2016: Journal of Neuroinflammation
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
Yu Zhang, Lin Cheng, Yajing Chen, Guo-Yuan Yang, Jianrong Liu, Lili Zeng
OBJECTIVE: We aim to explore the clinical factors and blood biomarker for predicting the early-onset post-stroke depression (PSD). METHODS: 251 acute ischemic stroke patients were divided into PSD group and non-PSD group by Hamilton depression scale in 2 weeks after stroke. The clinical data, the severity, etiology and location of stroke were recorded. The analysis of inflammatory mediator, glycose and lipid metabolism was performed on the day of admission. The association between clinical factors and early onset PSD was studied by logistic regression analysis...
March 15, 2016: Journal of Affective Disorders
Fu Jia Liu, Prameet Kaur, Dwi S Karolina, Sugunavathi Sepramaniam, Arunmozhiarasi Armugam, Peter T H Wong, Kandiah Jeyaseelan
Hypoxia inducible factor-1α facilitates cellular adaptation to hypoxic conditions. Hence its tight regulation is crucial in hypoxia related diseases such as cerebral ischemia. Changes in hypoxia inducible factor-1α expression upon cerebral ischemia influence the expression of its downstream genes which eventually determines the extent of cellular damage. MicroRNAs are endogenous regulators of gene expression that have rapidly emerged as promising therapeutic targets in several diseases. In this study, we have identified miR-335 as a direct regulator of hypoxia inducible factor-1α and as a potential therapeutic target in cerebral ischemia...
2015: PloS One
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
Vladimer Darsalia, Sansan Hua, Martin Larsson, Carina Mallard, David Nathanson, Thomas Nyström, Åke Sjöholm, Maria E Johansson, Cesare Patrone
Exendin-4 is a glucagon-like receptor 1 agonist clinically used against type 2 diabetes that has also shown neuroprotective effects in experimental stroke models. However, while the neuroprotective efficacy of Exendin-4 has been thoroughly investigated if the pharmacological treatment starts before stroke, the therapeutic potential of the Exendin-4 if the treatment starts acutely after stroke has not been clearly determined. Further, a comparison of the neuroprotective efficacy in normal and aged diabetic mice has not been performed...
2014: PloS One
Johnathan de Sousa Parreira, Ana Paula Kallaur, Marcio Francisco Lehmann, Sayonara Rangel Oliveira, Daniela Frizon Alfieri, Daniela Alfieri Frizon, Francieli Delongui, Franceili Delongui, Maria Caroline Martins de Araújo, Carolina Rossato, Jessica Tavares de Almeida, Larissa Muliterno Pelegrino, Erick Frank Bragato, Helena Kaminami Morimoto, Andrea Name Colado Simão, Damacio Ramon Kaimen-Maciel, Edna Maria Vissoci Reiche
Polymorphisms in genes coding for pro-inflammatory molecules represent important factors for the pathogenesis and outcome of stroke. The aim of this study was to evaluate the relationship between the tumor necrosis factor beta (TNF-β) NcoI (rs909253) polymorphism with inflammatory and metabolic markers in acute ischemic stroke. Ninety-three patients and 134 controls were included. The TNF-β polymorphism was determined using PCR-RFLP with NcoI restriction enzyme. Stroke subtypes and neurological deficit score were evaluated...
February 2015: Metabolic Brain Disease
Fabíola C R Zucchi, Youli Yao, Yaroslav Ilnytskyy, Jerrah C Robbins, Nasrin Soltanpour, Igor Kovalchuk, Olga Kovalchuk, Gerlinde A S Metz
Prenatal stress (PS) represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1) if PS modulates recovery following cortical ischemia in adulthood; (2) if a second hit by adult stress (AS) exaggerates stress responses and ischemic damage; and (3) if tactile stimulation (TS) attenuates the cumulative effects of PS and AS...
2014: PloS One
Shameena Bake, Amutha Selvamani, Jessica Cherry, Farida Sohrabji
Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1's neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1...
2014: PloS One
Dalbir K Dhiraj, Elvina Chrysanthou, Giovanna R Mallucci, Martin Bushell
Stroke, the loss of neurons after ischemic insult to the brain, is one of the leading causes of death and disability worldwide. Despite its prevalence and severity, current therapy is extremely limited, highlighting the importance of further understanding the molecular events underlying ischemia-induced neuronal cell death. An ischemic area can be subdivided into two separate pathophysiological regions: the rapidly dying necrotic core, and the potentially salvageable apoptotic penumbra. Understanding molecular events occurring in the apoptotic ischemic penumbra may give greater insight into mechanisms controlling this salvageable tissue...
2013: PloS One
Pawel Wolinski, Andrzej Glabinski
Neurodegeneration is a hallmark of most of the central nervous system (CNS) disorders including stroke. Recently inflammation has been implicated in pathogenesis of neurodegeneration and neurodegenerative diseases. The aim of this study was analysis of expression of several inflammatory markers and its correlation with development of neurodegeneration during the early stage of experimental stroke. Ischemic stroke model was induced by stereotaxic intracerebral injection of vasoconstricting agent endothelin-1 (ET-1)...
2013: Mediators of Inflammation
Hongwei Sun, Ying Tang, Xiqin Guan, Lanfeng Li, Desheng Wang
Hypothermia has neuroprotective effects on global cerebral ischemic injuries. However, its efficacy after intracerebral hemorrhage (ICH) is inconclusive. In this study, bacterial collagenase was used to induce ICH stroke in male Wistar rats. We assessed the effects of normothermia and 4 h of local hypothermia (~33.2°C) initiated 1, 6, or 12 h after collagenase infusion on hemorrhage volume and neurological outcomes. Following early cooling initiated after 1 h, blood-brain barrier (BBB) disruption and brain water content were tested...
October 2013: Biological Chemistry
Míriam Navarro-Sobrino, Mar Hernández-Guillamon, Israel Fernandez-Cadenas, Marc Ribó, Ignacio A Romero, Pierre-Olivier Couraud, Babette Barbash Weksler, Joan Montaner, Anna Rosell
BACKGROUND: The identification of circulating endothelial progenitor cells (EPCs) has introduced new possibilities for cell-based treatments for stroke. We tested the angiogenic gene expression of outgrowth endothelial cells (OECs), an EPC subtype capable to shape vessel structures. METHODS: OECs (at colony or mature stages) from ischemic stroke patients (n=8) were characterized using the RT2 ProfilerTM human angiogenesis PCR Array, and human microvascular endothelial cells (hCMEC/D3) were used as an expression reference of endothelial cells...
2013: Vascular Cell
Manuela Mengozzi, Ilaria Cervellini, Pia Villa, Zübeyde Erbayraktar, Necati Gökmen, Osman Yilmaz, Serhat Erbayraktar, Mathini Manohasandra, Paul Van Hummelen, Peter Vandenabeele, Yuti Chernajovsky, Alexander Annenkov, Pietro Ghezzi
Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and nervous system injury, where it reduces neuronal apoptosis and inflammatory cytokines and increases neurogenesis and angiogenesis. EPO also improves cognition in healthy volunteers and schizophrenic patients. We studied the effect of EPO administration on the gene-expression profile in the ischemic cortex of rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up-regulated genes already increased by ischemia...
June 12, 2012: Proceedings of the National Academy of Sciences of the United States of America
M Angels Font, Adriá Arboix, Jerzy Krupinski
Only very little is know about the neurovascular niche after cardioembolic stroke. Three processes implicated in neurorepair: angiogenesis, neurogenesis and synaptic plasticity, would be naturally produced in adult brains, but also could be stimulated through endogen neurorepair phenomena. Angiogenesis stimulation generates new vessels with the aim to increase collateral circulation. Neurogenesis is controlled by intrinsic genetic mechanisms and growth factors but also ambiental factors are important. The leading process of the migrating neural progenitor cells (NPCs) is closely associated with blood vessels, suggesting that this interaction provides directional guidance to the NPCs...
August 2010: Current Cardiology Reviews
An Zhou, Roger P Simon, Larry David
In a recent study on ischemic rodent brains, we quantitatively characterised and compared brain proteomes under ischemic-preconditioned or injured or tolerant conditions. We discovered an enriched presence of repressive transcriptional regulator proteins with essential roles as epigenetic regulators in ischemic-tolerant brains (Stapels et al., 2010). We further showed their robust, dynamic and differential changes under different ischemic conditions in brains and in cultured neuronal cells. In the present work, using neuronal cell cultures, we aimed to characterise the nascent proteome, the proteome that presents early when the cells receive an ischemic insult...
2011: International Journal of Computational Biology and Drug Design
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