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Stroke immune system

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https://www.readbyqxmd.com/read/28331857/thrombosis-neuroinflammation-and-poststroke-infection-the-multifaceted-role-of-neutrophils-in-stroke
#1
REVIEW
Johanna Ruhnau, Juliane Schulze, Alexander Dressel, Antje Vogelgesang
Immune cells can significantly predict and affect the clinical outcome of stroke. In particular, the neutrophil-to-lymphocyte ratio was shown to predict hemorrhagic transformation and the clinical outcome of stroke; however, the immunological mechanisms underlying these effects are poorly understood. Neutrophils are the first cells to invade injured tissue following focal brain ischemia. In these conditions, their proinflammatory properties enhance tissue damage and may promote ischemic incidences by inducing thrombus formation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28320635/safety-and-efficacy-of-multipotent-adult-progenitor-cells-in-acute-ischaemic-stroke-masters-a-randomised-double-blind-placebo-controlled-phase-2-trial
#2
David C Hess, Lawrence R Wechsler, Wayne M Clark, Sean I Savitz, Gary A Ford, David Chiu, Dileep R Yavagal, Ken Uchino, David S Liebeskind, Alexander P Auchus, Souvik Sen, Cathy A Sila, Jeffrey D Vest, Robert W Mays
BACKGROUND: Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA...
March 17, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28320030/changes-in-regulatory-t-cell-levels-in-acute-cerebral-ischemia
#3
Xuerui Pang, Weidong Qian
Background Acute stroke causes intense and significant changes in the immune system as well as in the number and the ratio of various immune cells. Material and Methods Several large-scale studies have shown that ischemic stroke leaves the human body in a state of immunodepression. The regulatory T (Treg) cells may be strongly associated with a change of immune status. In this trial, we collected venous blood from a cohort of patients who were diagnosed with acute ischemic stroke within the last 24 hours (n = 139)...
March 20, 2017: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/28315744/cardiac-implantable-electronic-device-infections-who-is-at-greatest-risk
#4
Parijat Saurav Joy, Gagan Kumar, Jeanne E Poole, Barry London, Brian Olshansky
BACKGROUND: Cardiac Implantable Electronic Device (CIED) infections are associated with hospitalization, mortality, increased costs and adverse outcomes. OBJECTIVE: Determine the burden of infections for CIEDs based on device type, associated comorbidities and clinical characteristics over a 12-year period. METHODS: Utilizing the National Inpatient Sample database from 2000-2012, procedures for device related infection (DRI) were identified using ICD-9-CM code for CIED removal with diagnosis codes for device-related infection or systemic infection...
March 15, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28314594/brain-ischemia-suppresses-immunity-in-the-periphery-and-brain-via-different-neurogenic-innervations
#5
Qiang Liu, Wei-Na Jin, Yaou Liu, Kaibin Shi, Haoran Sun, Fang Zhang, Chao Zhang, Rayna J Gonzales, Kevin N Sheth, Antonio La Cava, Fu-Dong Shi
Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28289923/tocilizumab-reverses-cerebral-vasculopathy-in-a-patient-with-homozygous-samhd1-mutation
#6
REVIEW
Michael Henrickson, Heng Wang
An auto-inflammatory syndrome consequent to SAMHD1 mutations involves cerebral vasculopathy characterized by multifocal stenosis and aneurysms within large arteries, moyamoya, chronic ischemia, and early-onset strokes (SAMS). While this condition involves the innate immune system, additional clinical features mimic systemic lupus erythematosus. Mutations in this gene can also cause a subset of the rare genetic condition Aicardi-Goutières syndrome. To date, no established therapy successfully prevents disease progression...
March 13, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28282924/autophagy-and-microglia-novel-partners-in-neurodegeneration-and-aging
#7
REVIEW
Ainhoa Plaza-Zabala, Virginia Sierra-Torre, Amanda Sierra
Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases...
March 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28263009/multipotent-adult-progenitor-cells-enhance-recovery-after-stroke-by-modulating-the-immune-response-from-the-spleen
#8
Bing Yang, Jason A Hamilton, Krystal S Valenzuela, Annelies Bogaerts, XiaoPei Xi, Jaroslaw Aronowski, Robert W Mays, Sean I Savitz
Stem cell therapy modulates not only the local microenvironment of the brain but also the systemic immune responses. We explored the impact of human multipotent adult progenitor cells (MAPC) modulating splenic activation and peripheral immune responses after ischemic stroke. Hundred twenty-six Long-Evans adult male rats underwent middle cerebral artery occlusion. Twenty-four hours later, they received IV MAPC or saline treatment. At 3 days after infusion, RNA was isolated from the injured cortex and spleen for microarray analysis...
March 6, 2017: Stem Cells
https://www.readbyqxmd.com/read/28253906/molecular-imaging-of-nestin-in-neuroinflammatory-conditions-reveals-marked-signal-induction-in-activated-microglia
#9
Senthil Krishnasamy, Yuan-Cheng Weng, Sai Sampath Thammisetty, Daniel Phaneuf, Melanie Lalancette-Hebert, Jasna Kriz
BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury...
March 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28248201/intravascular-hemolysis-and-the-pathophysiology-of-sickle-cell-disease
#10
REVIEW
Gregory J Kato, Martin H Steinberg, Mark T Gladwin
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28245997/contrasting-roles-of-immune-cells-in-tissue-injury-and-repair-in-stroke-the-dark-and-bright-side-of-immunity-in-the-brain
#11
REVIEW
Aditya Rayasam, Martin Hsu, Gianna Hernández, Julie Kijak, Anders Lindstedt, Christian Gerhart, Matyas Sandor, Zsuzsanna Fabry
Despite considerable efforts in research and clinical studies, stroke is still one of the leading causes of death and disability worldwide. Originally, stroke was considered a vascular thrombotic disease without significant immune involvement. However, over the last few decades it has become increasingly obvious that the immune responses can significantly contribute to both tissue injury and protection following stroke. Recently, much research has been focused on the immune system's role in stroke pathology and trying to elucidate the mechanism used by immune cells in tissue injury and protection...
February 25, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28176622/the-tlr9-antagonist-icpg-odn-at-different-dosages-inhibits-cerebral-ischemia-reperfusion-injury-in-mice
#12
Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong Dong, Lingna Deng Deng, Yidong Wang
Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear. This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion. Neurological function, infarct size, splenocytes and the expression of TLR9 and the downstream products of the TLR9 pathways were determined after cerebral I/R for up to 72 hours...
February 6, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28168424/characterization-of-dysregulated-mirna-in-peripheral-blood-mononuclear-cells-from-ischemic-stroke-patients
#13
Marpe Bam, Xiaoming Yang, Souvik Sen, Elizabeth E Zumbrun, Lauren Dennis, Jiajia Zhang, Prakash S Nagarkatti, Mitzi Nagarkatti
Epigenetic modification may play an important role in pathophysiology of ischemic stroke (IS) risk. MicroRNAs (miRNAs), which constitute one of the modes of epigenetic regulation, have been shown to be associated with a number of clinical disorders including IS. The purpose of this study was to investigate the miRNA profile in the peripheral blood mononuclear cells (PBMCs) of IS patients and compare it with stroke-free controls. Blood samples were obtained from 19 healthy age-gender-race matched individuals who served as controls to 20 IS patients...
February 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28155611/galectins-a-potential-target-for-cardiovascular-therapy
#14
Ghulam Md Ashraf, Asma Perveen, Syed Kashif Zaidi, Ausaf Ahmad, Shazi Shakil, Chelapram Kandy Firoz, Nasimudeen R Jabir, Iftekhar Hassan, Taqi Ahmad Khan, Nagendra Sastry Yarla, Shams Tabrez
Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell-cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of β-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28155595/cholinergic-anti-inflammatory-pathway-and-stroke
#15
Kamil Duris, Jolana Lipkova, Michal Jurajda
Stroke is devastating cerebrovascular event which is responsible for 6.7 million deaths each year worldwide. Inflammation plays an important role in the pathophysiology of stroke. Targeting inflammation after stroke is highly actual topic for both experimental and clinical research. Cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism by which central nervous system regulates immune response and controls inflammation. Vagus nerve, spleen and α7 nicotinic acetylcholine receptor (α7 nAChR) are the main components of CHAIP...
February 1, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28154551/prolonged-activation-of-invariant-natural-killer-t-cells-and-th2-skewed-immunity-in-stroke-patients
#16
Connie H Y Wong, Craig N Jenne, Patrick P Tam, Caroline Léger, Andres Venegas, Karla Ryckborst, Michael D Hill, Paul Kubes
BACKGROUND: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28142307/misdirected-sympathy
#17
Jason A Ferreira, Brittany D Bissell
The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/28139706/identification-of-mirna-lncrna-and-mrna-associated-cerna-networks-and-potential-biomarker-for-melas-with-mitochondrial-dna-a3243g-mutation
#18
Wei Wang, Qianqian Zhuang, Kunqian Ji, Bing Wen, Pengfei Lin, Yuying Zhao, Wei Li, Chuanzhu Yan
Researchers in the field of mitochondrial biology are increasingly unveiling of the complex mechanisms between mitochondrial dysfunction and noncoding RNAs (ncRNAs). However, roles of ncRNAs underlying mitochondrial myopathy remain unexplored. The aim of this study was to elucidate the regulating networks of dysregulated ncRNAs in Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) with mitochondrial DNA (mtDNA) A3243G mutation, which might make contributions to the unveiling of the complex mechanisms underlying mitochondrial myopathy and, possibly, new tools applicable to clinical practice...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135006/contribution-of-maladaptive-adipose-tissue-expansion-to-development-of-cardiovascular-disease
#19
Guanghong Jia, Yan Jia, James R Sowers
The overweight and obesity epidemic has led to an increase in the metabolic syndrome and associated cardiovascular disease (CVD). These abnormalities include insulin resistance, type 2 diabetes mellitus, vascular stiffness, hypertension, stroke, and coronary heart disease. Visceral white adipocyte tissue (WAT) expansion and associated fibrosis/stiffness of WAT promote insulin resistance and CVD through increases in proinflammatory adipokines, oxidative stress, activation of renin-angiotensin-aldosterone system, dysregulation of adipocyte apoptosis and autophagy, dysfunctional immune modulation, and adverse changes in the gut microbiome...
December 6, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/28115719/immunoinhibitory-checkpoint-deficiency-in-medium-and-large-vessel-vasculitis
#20
Hui Zhang, Ryu Watanabe, Gerald J Berry, Augusto Vaglio, Yaping Joyce Liao, Kenneth J Warrington, Jörg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) causes autoimmune inflammation of the aorta and its large branches, resulting in aortic arch syndrome, blindness, and stroke. CD4(+) T cells and macrophages form organized granulomatous lesions in the walls of affected arteries, destroy the tunica media, and induce ischemic organ damage through rapid intimal hyperplasia and luminal occlusion. Pathogenic mechanisms remain insufficiently understood; specifically, it is unknown whether the unopposed activation of the immune system is because of deficiency of immunoinhibitory checkpoints...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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