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Neutrophil stroke

Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
İsa Öner Yüksel, Erkan Köklü, Şakir Arslan, Göksel Çağırcı, Eylem Özaydın Göksu, Pınar Koç, Serkan Çay, Filiz Kızılırmak
BACKGROUND AND OBJECTIVES: Non-calcified carotid plaques are more unstable than calcified plaques, and they are associated with a higher risk of rupture, thromboembolism, and consequently, stroke. The purpose of the present study is to compare calcified and non-calcified plaques that cause intermediate carotid artery stenosis with respect to neutrophil/lymphocyte ratio (NLR). SUBJECTS AND METHODS: A total number of 139 asymptomatic patients with 50-70% stenosis of the carotid artery were included in this study...
September 2016: Korean Circulation Journal
Poonam Malhotra Kapoor, Rohan Magoon, Rajinder Rawat, Yatin Mehta
Goal-directed therapy (GDT) encompasses guidance of intravenous (IV) fluid and vasopressor/inotropic therapy by cardiac output or similar parameters to help in early recognition and management of high-risk cardiac surgical patients. With the aim of establishing the utility of perioperative GDT using robust clinical and biochemical outcomes, we conducted the present study. This multicenter randomized controlled study included 130 patients of either sex, with European system for cardiac operative risk evaluation ≥3 undergoing coronary artery bypass grafting on cardiopulmonary bypass...
October 2016: Annals of Cardiac Anaesthesia
Christopher W L Armstrong, Erika Bosio, Claire Neil, Simon G A Brown, Graeme J Hankey, Daniel M Fatovich
We previously reported on a 26-year-old patient who presented early during a large and eventually fatal cerebral infarct. Microarray analysis of blood samples from this patient demonstrated initially up-regulated and subsequently down-regulated Granzyme B (GzmB) expression, along with progressive up-regulation of genes for S100 calcium binding protein A12 (S100A12) and matrix metalloproteinase 9 (MMP-9). To confirm these findings, we investigated these parameters in patients with suspected stroke presenting within 6h of symptom onset to a single centre...
September 30, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Jiannan Chen, Xiangjian Zhang, Cong Zhang, Wenhui Wang, Rong Chen, Honglei Jiao, Linlin Li, Lan Zhang, Lili Cui
Inflammation after stroke consists of activation of microglia/astrocytes in situ and infiltration of blood-borne leukocytes, resulting in brain damage and neurological deficits. Mounting data demonstrated that most natural components from medicinal plants had anti-inflammatory effects after ischemic stroke through inhibiting activation of resident microglia/astrocytes within ischemic area. However, it is speculated that this classical activity cannot account for the anti-inflammatory function of these natural components in the cerebral parenchyma, where they are detected at very low concentrations due to their poor membrane permeability and slight leakage of BBB...
2016: Mediators of Inflammation
Starlee Lively, Sarah Hutchings, Lyanne C Schlichter
Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew the brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces an anti-inflammatory, "alternative-activation" state in microglia and macrophages in vitro, we tested the hypothesis that early supplementation of the brain with IL-4 can shift it toward an anti-inflammatory state and reduce damage after transient focal ischemia...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
Yifang Fan, Xiaoxing Xiong, Yongming Zhang, Dongmei Yan, Zhihong Jian, Baohui Xu, Heng Zhao
BACKGROUND: MKEY, a synthetic cyclic peptide inhibitor of CXCL4-CCL5 heterodimer formation, has been shown to protect against atherosclerosis and aortic aneurysm formation by mediating inflammation, but whether it modulates neuroinflammation and brain injury has not been studied. We therefore studied the role of MKEY in stroke-induced brain injury in mice. METHODS AND RESULTS: MKEY was injected into mice after stroke with 60 minutes of middle cerebral artery occlusion...
September 2016: Journal of the American Heart Association
Nina L Chiu, Brian Kaiser, Y Vien Nguyen, Susan Welbourne, Chandana Lall, Steven C Cramer
BACKGROUND: Animal studies describe changes in the spleen following a stroke, with an immediate reduction in volume associated with changes in the counts of specific blood white blood cell (WBCs). This brain-spleen cell cycling after stroke affects systemic inflammation and the brain inflammatory milieu and may be a target for emerging therapeutic studies. This study aimed to evaluate features of this brain-spleen model in human patients admitted for acute stroke. METHODS: Medical and imaging records were retrospectively reviewed for 82 consecutive patients admitted for acute stroke in whom an abdominal computed tomography scan was performed...
September 5, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
J H Tapia-Pérez, D Karagianis, R Zilke, V Koufuglou, I Bondar, T Schneider
OBJECTIVE: After spontaneous intracerebral hemorrhage (ICH) a local and systemic inflammatory response is activated. Interleukin-6 (IL) is one of most relevant orchestrators of inflammatory responses in the brain and is released from multiple immune cells, including neutrophils. Herby we assessed the relevance of systemic inflammation in patients suffering ICH. METHODS: From October 2010 to October 2011 we included in our routine of laboratory investigations besides to C-reactive protein (CRP), the addition of IL-6 and an analysis of the subpopulation of circulating blood cells...
November 2016: Clinical Neurology and Neurosurgery
Xiaoxing Xiong, Lijuan Gu, Yan Wang, Ying Luo, Hongfei Zhang, Jessica Lee, Sheri Krams, Shengmei Zhu, Heng Zhao
BACKGROUND: Glycyrrhizin (Gly) protects against brain injury induced by stroke. We studied whether Gly achieves its protection by inhibiting T cell activity and high-mobility group box 1 (HMGB1) release in the ischemic brain. METHODS: Stroke was induced by transient middle cerebral artery occlusion in rats and mice. Gly was injected intraperitoneally before or after stroke. We measured infarction, neuroinflammatory cells, gene expressions of interferon-γ (IFNγ), IL-4, and IL-10 in CD4 T cells, HMGB1 release, and T cell proliferation in cultured splenocytes...
2016: Journal of Neuroinflammation
Roberta Caorsi, Federica Penco, Francesca Schena, Marco Gattorno
The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease characterised by an early onset vasculopathy with livedoid skin rash associated with systemic manifestations, CNS involvement and mild immunodeficiency.This condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different mutations in CECR1 gene have been detected...
2016: Pediatric Rheumatology Online Journal
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
Zhiliang Guo, Shuhong Yu, Lulu Xiao, Xin Chen, Ruidong Ye, Ping Zheng, Qiliang Dai, Wen Sun, Changsheng Zhou, Shuiping Wang, Wusheng Zhu, Xinfeng Liu
BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. METHODS: A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT...
2016: Journal of Neuroinflammation
Kyungdong Min, Seungwon Kwon, Seung-Yeon Cho, Woo Jun Choi, Seong-Uk Park, Woo-Sang Jung, Sang-Kwan Moon, Jung-Mi Park, Chang-Nam Ko, Ki-Ho Cho
BACKGROUND: No study has investigated the relationship between hospital-admission neutrophil and lymphocyte ratio (NLR) and various stroke risk factors. We sought to determine which stroke risk factor could be the most appropriate predictor of NLR in acute ischemic stroke. METHODS: We collected data on various stroke risk factors and National Institutes of Health Stroke Scale (NIHSS) score in 1,053 acute ischemic stroke patients. The regression analysis was adjusted for confounding factors such as stroke risk factors...
August 25, 2016: Journal of Clinical Laboratory Analysis
Nirav Dhanesha, Prem Prakash, Prakash Doddapattar, Ira Khanna, Molly J Pollpeter, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: von Willebrand factor (VWF), which is synthesized in endothelial cells and megakaryocytes, is known to worsen stroke outcome. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically different from the endothelial cell-derived VWF (EC-VWF). However, little is known about relative contribution of different pools of VWF in stroke. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF mice, Plt-VWF mice that lack ADAMTS13 in platelets and plasma (Plt-VWF/Adamts13(-/-)), and EC-VWF mice to determine relative contribution of different pools of VWF in stroke...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
T Wun
Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes...
2000: Hematology (Amsterdam, Netherlands)
Roland Veltkamp, Dipender Gill
Inflammatory mechanisms are currently considered as a prime target for stroke therapy. There is evidence from animal studies that immune signals and mediators can have both detrimental and beneficial effects in particular stages of the disease process. Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. Several clinical proof-of concept trials have investigated the efficacy of different immunomodulatory approaches in patients with stroke...
July 13, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Hui Wang, Jason S Knight, Jeffrey B Hodgin, Jintao Wang, Chiao Guo, Kyle Kleiman, Daniel T Eitzman
Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1(-/-)) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls...
2016: Scientific Reports
Adrian Brun, Hélène Rangé, Bastien Prouvost, Olivier Meilhac, Mikael Mazighi, Pierre Amarenco, Guy Lesèche, Philippe Bouchard, Jean-Baptiste Michel
Periodontal diseases are multifactorial inflammatory diseases, caused by a bacterial biofilm involving both innate and adaptative immunity, characterized by the destruction of tooth-supporting tissues. In the context of periodontitis, the spread of weak pathogenic bacteria into the bloodstream has been described. These bacteria will preferentially localize to existing clot within the circulation. Atherothrombosis of the carotid arteries is a local pathology and a common cause of cerebral infarction. Intraplaque hemorrhages render the lesion more prone to clinical complications such as stroke...
2016: Bulletin du Groupèment International Pour la Recherche Scientifique en Stomatologie & Odontologie
Sean X Gu, Ilya O Blokhin, Katina M Wilson, Nirav Dhanesha, Prakash Doddapattar, Isabella M Grumbach, Anil K Chauhan, Steven R Lentz
Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII)...
2016: JCI Insight
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