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  1. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

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    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  2. Ischemic preconditioning protects against ischemic brain injury

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    Xiao-meng Ma

    2016-01-01

    Full Text Available In this study, we hypothesized that an increase in integrin αv ß 3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αv ß 3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αv ß 3 and vascular endothelial growth factor levels in the brain following ischemia.

  3. Remote Ischemic Conditioning and Renal Protection.

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    Giannopoulos, Georgios; Vrachatis, Dimitrios A; Panagopoulou, Vasiliki; Vavuranakis, Manolis; Cleman, Michael W; Deftereos, Spyridon

    2017-07-01

    Over the course of the last 2 decades, the concept of remote ischemic conditioning (RIC) has attracted considerable research interest, because RIC, in most of its embodiments offers an inexpensive way of protecting tissues against ischemic damage inflicted by a number of medical conditions or procedures. Acute kidney injury (AKI) is a common side effect in the context of various medical procedures, and RIC has been suggested as a means of reducing its incidence. Outcomes regarding kidney function have been reported in numerous studies that evaluated the effects of RIC in a variety of settings (eg, cardiac surgery, interventions requiring intravenous administration of contrast media). Although several individual studies have implied a beneficial effect of RIC in preserving kidney function, 3 recently published randomized controlled trials evaluating more than 1000 patients each (Effect of Remote Ischemic Preconditioning in the Cardiac Surgery, Remote Ischaemic Preconditioning for Heart Surgery, and ERICCA) were negative. However, AKI or any other index of renal function was not a stand-alone primary end point in any of these trials. On the other hand, a range of meta-analyses (each including thousands of participants) have reported mixed results, with the most recent among them showing benefit from RIC, pinpointing at the same time a number of shortcomings in published studies, adversely affecting the quality of available data. The present review provides a critical appraisal of the current state of this field of research. It is the opinion of the authors of this review that there is a clear need for a common clinical trial framework for ischemic conditioning studies. If the current babel of definitions, procedures, outcomes, and goals persists, it is most likely that soon ischemic conditioning will be "yesterday's news" with no definitive conclusions having been reached in terms of its real clinical utility.

  4. Protective effects of ischemic postconditioning on intestinal

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    DING Jun-tao

    2011-04-01

    Full Text Available 【Abstract】Objective: To explore the protective effects of two types of ischemic postconditioning (IP on intestinal mucosa barrier in rabbits with crush injury of the hind limb. Methods: This study was conducted between August and December 2008 in the Department of Trauma Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. The model of crush injury to the hind limb of rabbits was firstly developed by a 25 kg object with the right hind limbs fixed by wooden splints, and then two types of IP were established, including occluding/opening the common iliac artery and vein alternatively (traditional IP, IP A and binding/loosening the proximum of the injured hind limb alternatively (modified IP, IP B. Thirty-six male New Zealand white rabbits were randomly divided into three groups: IP A group, IP B group and control group, with 12 rabbits in each group. The serum levels of diamine oxidase (DAO and intestinal fatty acid-binding protein (I-FABP were detected at 2, 6, 12 and 24 hours after injury. Pathological changes of ileum were examined at 24 hours after injury. Results: The serum levels of I-FABP at 2, 6, 12 and 24 hours after injury in both IP A and IP B groups had a significant decrease, compared with control group. DAO levels also showed the same change trend at 2 and 6 hours after injury, but showed no significant difference between two IP groups. No difference in pathological changes of ileum was found among the three groups. Conclusions: IP can protect intestinal mucosa barrier function on the model of hind limb crush injury in rabbits. Meanwhile the modified IP B shows the same protection as the traditional IP A, and is worth applying in clinic. Key words: Ischemic postconditioning; Crush syndrome; Intestinal mucosa

  5. The relation of thrombomodulin G33A and C1418T gene ...

    African Journals Online (AJOL)

    Background: Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. There is an increased interest in the genetic risk factors in the pathogenesis of ischemic heart disease. Thrombomodulin (TM), a natural anticoagulant, may play a critical role in the pathogenesis of AMI. Aim of the ...

  6. Protective effects of incensole acetate on cerebral ischemic injury.

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    Moussaieff, Arieh; Yu, Jin; Zhu, Hong; Gattoni-Celli, Sebastiano; Shohami, Esther; Kindy, Mark S

    2012-03-14

    The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage. Published by Elsevier B.V.

  7. The protective effect of ischemic preconditioning on rat testis

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    Ciralik Harun

    2007-12-01

    Full Text Available Abstract Background It has been demonstrated that brief episodes of sublethal ischemia-reperfusion, so-called ischemic preconditioning, provide powerful tissue protection in different tissues such as heart, brain, skeletal muscle, lung, liver, intestine, kidney, retina, and endothelial cells. Although a recent study has claimed that there are no protective effects of ischemic preconditioning in rat testis, the protective effects of ischemic preconditioning on testicular tissue have not been investigated adequately. The present study was thus planned to investigate whether ischemic preconditioning has a protective effect on testicular tissue. Methods Rats were divided into seven groups that each contained seven rats. In group 1 (control group, only unilateral testicular ischemia was performed by creating a testicular torsion by a 720 degree clockwise rotation for 180 min. In group 2, group 3, group 4, group 5, group 6, and group 7, unilateral testicular ischemia was performed for 180 min following different periods of ischemic preconditioning. The ischemic preconditioning periods were as follows: 10 minutes of ischemia with 10 minutes of reperfusion in group 2; 20 minutes of ischemia with 10 minutes of reperfusion in group 3; 30 minutes of ischemia with 10 minutes of reperfusion in group 4; multiple preconditioning periods were used (3 × 10 min early phase transient ischemia with 10 min reperfusion in all episodes in group 5; multiple preconditioning periods were used (5, 10, and 15 min early phase transient ischemia with 10 min reperfusion in all episodes in group 6; and, multiple preconditioning periods were used (10, 20, and 30 min early phase transient ischemia with 10 min reperfusion in all episodes in group 7. After the ischemic protocols were carried out, animals were sacrificed by cervical dislocation and testicular tissue samples were taken for biochemical measurements (protein, malondialdehyde, nitric oxide and histological examination

  8. [The protective action of nimodipine on the ischemic myocardium].

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    Tsorin, I B; Kazanova, G V; Kirsanova, G Iu; Chirkova, E Iu; Chichkanov, G G

    1992-01-01

    The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation.

  9. Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

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    Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

    2004-01-01

    Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

  10. Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

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    Mowat, Freya M; Gonzalez, Francisco; Luhmann, Ulrich F O; Lange, Clemens A; Duran, Yanai; Smith, Alexander J; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

    2012-04-01

    Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

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    Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

    2011-11-01

    We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (Pknock-in mice compared with wild-type mice (Pknock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; Pknock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

  12. The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways

    NARCIS (Netherlands)

    Conway, Edward M.; van de Wouwer, Marlies; Pollefeyt, Saskia; Jurk, Kerstin; van Aken, Hugo; de Vriese, Astrid; Weitz, Jeffrey I.; Weiler, Hartmut; Hellings, Peter W.; Schaeffer, Paul; Herbert, Jean-Marc; Collen, Désiré; Theilmeier, Gregor

    2002-01-01

    Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a cofactor for thrombin-mediated activation of the anticoagulant protein C. The extracellular NH(2)-terminal domain of TM has homology to C-type lectins that are involved in immune regulation. Using transgenic mice that lack

  13. Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

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    Jiangwei Ma

    2012-03-01

    Full Text Available Brief episodes of myocardial ischemia-reperfusion (IR employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK, lactate dehydrogenase (LDH and aspartate transaminase (AST activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px and glutathione reductase (GR activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

  14. Cerebrovascular ischemic protection by pre- and post-conditioning

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    Jeffrey M Gidday

    2015-01-01

    Full Text Available Stroke and cardiac arrest involve injury to all the brain′s resident cells and their respective progenitors, including neurons, all glial subtypes, vascular smooth muscle, vascular endothelium, and pericytes, resulting either in the death of the individual or in a lesion that likely manifests as long-term impairments across a number of cognitive and functional domains. Thousands of studies in experimental animals and results from a few clinical trials in humans have demonstrated that the mechanisms responsible for ischemic brain injury can be blocked or slowed by survival-enhancing epigenetic responses induced by "conditioning" the brain with a stress stimulus paradigm before or even after ictus. The resultant reduction in lesion size and functional deficits are often termed endogenous "neuroprotection," but this in fact involves cytoprotective responses on the part of all the aforementioned resident brain cells and the circulating immune cells as well. The present review will summarize findings demonstrating conditioning-induced protection of the cerebral vasculature, that in turn manifests as reductions in vascularly targeted inflammatory responses; less endothelial injury and improvements in structural integrity of the circulation across all levels of organization; enhanced perfusion with less thrombosis; reductions in vascular dysregulation and reactivity impairments; and, over the longer term, more robust angiogenesis and vascular remodeling. Advancing the mechanistic basis for these innately vasculoprotective phenotypes may provide therapeutic targets for limiting cerebral circulatory injury and dysfunction following stroke and cardiac arrest.

  15. Sodium 4-phenylbutyrate protects against cerebral ischemic injury.

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    Qi, Xin; Hosoi, Toru; Okuma, Yasunobu; Kaneko, Masayuki; Nomura, Yasuyuki

    2004-10-01

    Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.

  16. Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

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    Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

    2016-04-01

    Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (Ppreeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (Ppreeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

  17. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

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    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  18. Neonatal rat hearts cannot be protected by ischemic postconditioning

    Czech Academy of Sciences Publication Activity Database

    Doul, J.; Charvátová, Z.; Ošťádalová, Ivana; Kohutiar, M.; Maxová, H.; Ošťádal, Bohuslav

    2015-01-01

    Roč. 64, č. 6 (2015), s. 789-794 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : neonatal rats * ischemic postconditioning * tolerance to ischemia * contractile function * lactate dehydrogenase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  19. Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

    Science.gov (United States)

    Kolb, Alexander L; Corridon, Peter R; Zhang, Shijun; Xu, Weimin; Witzmann, Frank A; Collett, Jason A; Rhodes, George J; Winfree, Seth; Bready, Devin; Pfeffenberger, Zechariah J; Pomerantz, Jeremy M; Hato, Takashi; Nagami, Glenn T; Molitoris, Bruce A; Basile, David P; Atkinson, Simon J; Bacallao, Robert L

    2018-04-01

    Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine ( P <0.05) observed in controls and increased the mitochondria membrane potential ( P <0.05), maximal respiratory capacity ( P <0.05), and intracellular ATP levels ( P <0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning. Copyright © 2018 by the American Society of Nephrology.

  20. Thrombomodulin inhibits the activation of eosinophils and mast cells.

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    Roeen, Ziaurahman; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Onishi, Masahiro; Kobayashi, Tetsu; Yasuma, Taro; Urawa, Masahito; Taguchi, Osamu; Gabazza, Esteban C

    2015-01-01

    Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM-Mediated Protection of Ischemic Brain.

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    Chi-Hsin Lin

    Full Text Available The protective value of neuron-derived conditioned medium (NCM in cerebral ischemia and the underlying mechanism(s responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO animal model, we discovered that ischemia/reperfusion (I/R-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.

  2. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    Science.gov (United States)

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  3. Systemic protection through remote ischemic preconditioning is spread by platelet-dependent signaling in mice.

    Science.gov (United States)

    Oberkofler, Christian E; Limani, Perparim; Jang, Jae-Hwi; Rickenbacher, Andreas; Lehmann, Kuno; Raptis, Dimitri A; Ungethuem, Udo; Tian, Yinghua; Grabliauskaite, Kamile; Humar, Rok; Graf, Rolf; Humar, Bostjan; Clavien, Pierre-Alain

    2014-10-01

    Remote ischemic preconditioning (RIPC), the repetitive transient mechanical obstruction of vessels at a limb remote to the operative site, is a novel strategy to mitigate distant organ injury associated with surgery. In the clinic, RIPC has demonstrated efficacy in protecting various organs against ischemia reperfusion (IR), but a common mechanism underlying the systemic protection has not been identified. Here, we reasoned that protection may rely on adaptive physiological responses toward local stress, as is incurred through RIPC. Standardized mouse models of partial hepatic IR and of RIPC to the femoral vascular bundle were applied. The roles of platelets, peripheral serotonin, and circulating vascular endothelial growth factor (Vegf) were studied in thrombocytopenic mice, Tph1(-) (/) (-) mice, and through neutralizing antibodies, respectively. Models of interleukin-10 (Il10) and matrix metalloproteinase 8 (Mmp8) deficiency were used to assess downstream effectors of organ protection. The protection against hepatic IR through RIPC was dependent on platelet-derived serotonin. Downstream of serotonin, systemic protection was spread through up-regulation of circulating Vegf. Both RIPC and serotonin-Vegf induced differential gene expression in target organs, with Il10 and Mmp8 displaying consistent up-regulation across all organs investigated. Concerted inhibition of both molecules abolished the protective effects of RIPC. RIPC was able to mitigate pancreatitis, indicating that it can protect beyond ischemic insults. We have identified a platelet-serotonin-Vegf-Il10/Mmp8 axis that mediates the protective effects of RIPC. The systemic action, the conservation of RIPC effects among mice and humans, and the protection beyond ischemic insults suggest that the platelet-dependent axis has evolved as a preemptive response to local stress, priming the body against impending harm. © 2014 by the American Association for the Study of Liver Diseases.

  4. Perioperative erythropoietin protects the CNS against ischemic lesions in patients after open heart surgery.

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    Lakič, Nikola; Mrak, Miha; Šušteršič, Miha; Rakovec, Peter; Bunc, Matjaž

    2016-12-01

    The aim of this study was to establish erythropoietin as a protective factor against brain ischemia during open heart surgery. A total of 36 consecutive patients scheduled for revascularization heart surgery were included in the study. Of the patients 18 received 3 intravenous doses of recombinant human erythropoietin (rHuEpo, 24,000 IU) and 18 patients received a placebo. Magnetic resonance imaging (MRI) to detect new brain ischemic lesions was performed. Additionally, S100A, S100B, neuron-specific enolase A and B (NSE-A and B) and the concentration of antibodies against N‑methyl-D-aspartate receptors (NMDAR) to identify new neurological complications were determined. Patients who received rHuEpo showed no postoperative ischemic changes in the brain on MRI images. In the control group 5 (27.8 %) new ischemic lesions were found. The NMDAR antibody concentration, S100A, S100B and NSE showed no significant differences between the groups for new cerebral ischemia. High levels of lactate before and after external aortic compression (p = 0.022 and p = 0.048, respectively) and duration of operation could predict new ischemic lesions (p = 0.009). The addition of rHuEpo reduced the formation of lesions detectable by MRI in the brain and could be used clinically as neuroprotection in cardiac surgery.

  5. Is beta-thalassemia trait a protective factor against ischemic cerebrovascular accidents?

    Science.gov (United States)

    Karimi, Mehran; Borhani Haghighi, Afshin; Yazdani, Maryam; Raisi, Hamideh; Giti, Rahil; Namazee, Mohammad Reza

    2008-01-01

    In this research, we sought to determine the association between beta-thalassemia trait and ischemic cerebrovascular accident (CVA). In acase-control study, 148 patients with thromboembolic cerebrovascular events were evaluated for the presence of hypertension, diabetes mellitus, hyperlipidemia, and beta-thalassemia trait. A total of 156 age- and sex-matched patients with no cardiac or cerebrovascular diseases, serving as the control group, were also investigated for the above-mentioned risk factors. We found that 6.1% of patients with ischemic CVA and 12.2% of the control group had beta-thalassemia trait (P = .066). In male patients, the negative association between ischemic CVA and presence of beta-thalassemia trait was significant (P = .008). In patients, the prevalence of hypertension was also significantly different between those with and without beta-thalassemia trait (P = .01); those with beta-thalassemia trait had a lower mean blood pressure than those without the trait. beta-Thalassemia trait may have a protective effect against ischemic CVA that might be caused by the lower arterial blood pressure observed in those with this trait.

  6. Thrombomodulin expression regulates tumorigenesis in bladder cancer

    International Nuclear Information System (INIS)

    Wu, Chun-Te; Chang, Ying-Hsu; Lin, Paul- Yang; Chen, Wen-Cheng; Chen, Miao-Fen

    2014-01-01

    The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer

  7. The Potential of Tetrandrine as a Protective Agent for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Sheng-Hong Tseng

    2011-09-01

    Full Text Available Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

  8. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    International Nuclear Information System (INIS)

    Jing, Xu; Ren, Dongmei; Wei, Xinbing; Shi, Huanying; Zhang, Xiumei; Perez, Ruth G.; Lou, Haiyan; Lou, Hongxiang

    2013-01-01

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury

  9. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Xu [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Ren, Dongmei [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China); Wei, Xinbing; Shi, Huanying; Zhang, Xiumei [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Perez, Ruth G. [Health Science Center, Paul L. Foster School of Medicine, Texas Tech University, El Paso, TX, 79905 (United States); Lou, Haiyan, E-mail: louhaiyan@sdu.edu.cn [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Lou, Hongxiang [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China)

    2013-12-15

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury.

  10. Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model.

    Science.gov (United States)

    Kitamura, Youji; Iida, Yasuhiko; Abe, Jun; Ueda, Masashi; Mifune, Masaki; Kasuya, Fumiyo; Ohta, Masayuki; Igarashi, Kazuo; Saito, Yutaka; Saji, Hideo

    2006-02-01

    In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 microM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 microM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.

  11. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

    Science.gov (United States)

    Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

    2004-04-01

    Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, PhHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

  12. Stachys sieboldii (Labiatae, Chorogi) Protects against Learning and Memory Dysfunction Associated with Ischemic Brain Injury.

    Science.gov (United States)

    Harada, Shinichi; Tsujita, Tsukasa; Ono, Akiko; Miyagi, Kei; Mori, Takaharu; Tokuyama, Shogo

    2015-01-01

    Stachys sieboldii (Labiatae; Chinese artichoke, a tuber), "chorogi" in Japanese, has been extensively used in folk medicine, and has a number of pharmacological properties, including antioxidative activity. However, few studies have examined the neuroprotective effects of S. sieboldii tuber extract (chorogi extract), and it remains unknown whether the extract can alleviate learning and memory dysfunction associated with vascular dementia or Alzheimer's disease. Therefore, in this study, we investigated the neuroprotective effects of chorogi extract, and examined its protection against learning and memory dysfunction using Ginkgo biloba leaf extract (ginkgo extract) as a positive control. Mice were subjected to bilateral carotid artery occlusion (BCAO) for 30 min. Oral administration of chorogi extract or ginkgo extract significantly reduced post-ischemic glucose intolerance on day 1 and neuronal damage including memory impairment on day 3 after BCAO, compared with the vehicle-treated group. Neither herbal medicine affected locomotor activity. Furthermore, neither significantly alleviated scopolamine-induced learning and memory impairment. In primary neurons, neuronal survival rate was significantly reduced by hydrogen peroxide treatment. This hydrogen peroxide-induced neurotoxicity was significantly suppressed by chorogi extract and ginkgo extract. Taken together, our findings suggest that chorogi extract as well as ginkgo extract can protect against learning and memory dysfunction associated with ischemic brain injury through an antioxidative mechanism.

  13. Subclinical ischemic events in patients undergoing carotid artery stent placement: comparison of proximal and distal protection techniques.

    Science.gov (United States)

    Aytac, Emrah; Gürkaş, Erdem; Akpinar, Cetin Kursad; Saleem, Muhammad A; Qureshi, Adnan I

    2017-10-01

    To determine the relative effectiveness of proximal and distal protection in prevention of cerebral ischemic events during carotid artery stent (CAS) placement using diffusion-weighted MRI (DW-MRI). We analyzed data from patients who had undergone DW-MRI before and within 24 hours of CAS for symptomatic internal carotid artery (ICA) stenosis (with last ischemic events within 3 months). The study was performed prospectively; patients were not randomized, and were treated either with a proximal balloon occlusion system (Mo.Ma; Invatec, Roncadelle, Italy) or filter-type distal protection device (Spider device; ev3, Plymouth, Minnesota, USA). Of the 45 patients (mean age±SD: 66.9±9.8 years; 73.3% were men) who underwent CAS, 19 had proximal protection and 26 distal protection. New ischemic lesions were detected in 26/45 patients on DW-MRI scans obtained within 24 hours after CAS. The proportion of patients with new lesions on DW-MRI at 24 hours was not different between the two groups (47.4% vs 65.4% for proximal and distal protection, respectively). The mean number of new ischemic lesions on post-CAS DW-MRI was non-significantly higher in patients who underwent CAS with distal protection (2.80±3.54 for proximal protection vs 4.96±5.11 for distal protection; p=0.12). The proportion of patients with new lesions >1 cm did not differ between the two groups (5.3% for proximal protection vs 11.5% for distal protection; p=0.62). There was no difference in the rates of ischemic stroke between patients who underwent CAS treatment using proximal and distal protection (5.3% vs 7.7%; p=1.000). We found a relatively high rate of new ischemic lesions in patients undergoing CAS with cerebral protection. There was no difference in the proportion of patients with new lesions between patients treated using distal protection and those treated using proximal protection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  14. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

    Science.gov (United States)

    Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

    2013-01-01

    Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

  15. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

    Science.gov (United States)

    Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

    2006-11-01

    Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

  16. Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

    Science.gov (United States)

    Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

    2015-01-01

    Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

  17. The role of 17-beta estradiol in ischemic preconditioning protection of the heart.

    Science.gov (United States)

    Babiker, Fawzi A; Hoteit, Lamia J; Joseph, Shaji; Mustafa, Abu Salim; Juggi, Jasbir S

    2012-09-01

    The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated. To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury. SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed. IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not. Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.

  18. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE

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    Benjamin Harding

    2016-12-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI insult in neonatal rats via intracerebroventricular (ICV injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional

  19. Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

    Science.gov (United States)

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-10-17

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  20. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Zhong-Xin Xu

    2013-10-01

    Full Text Available Activin A (ActA, a member of transforming growth factor-beta (TGF-b super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab. We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  1. In vivo behavior of detergent-solubilized purified rabbit thrombomodulin on intravenous injection into rabbits

    International Nuclear Information System (INIS)

    Ehrlich, H.J.; Esmon, N.L.; Bang, N.U.

    1990-01-01

    Thrombomodulin is a thrombin endothelial cell membrane receptor. The thrombomodulin-thrombin complex rapidly activates protein C resulting in anticoagulant activity. We investigated the anticoagulant effects and pharmacokinetic behavior of detergent-solubilized purified rabbit thrombomodulin labeled with iodine 125 when intravenously injected into rabbits. Thrombomodulin half-life (t1/2) was determined by tracking the 125I-radiolabeled protein and the biologic activity as determined by the prolongation of the activated partial thromboplastin time (APTT) and thrombin clotting time (TCT). When 200 micrograms/kg 125I-thrombomodulin was injected into rabbits, the APTT and TCT were immediately prolonged, whereas no effect on the prothrombin time was seen. In vitro calibration curves enabled us to convert the prolongations of the clotting times into micrograms per milliliter thrombomodulin equivalents. The best fit (r greater than 0.99) for the disappearance curves was provided by a two-compartment model with mean t1/2 alpha (distribution phase) of 18 minutes for 125I, 12 minutes for APTT, and 20 minutes for TCT, and mean t1/2 beta (elimination phase) of 385 minutes for 125I, 460 for APTT, and 179 for TCT. The administration of two doses of endotoxin (50 micrograms/kg) 24 hours apart did not accelerate the turnover rate of 125I-thrombomodulin as measured by the disappearance of 125I from the circulation. Thus, detergent-solubilized purified thrombomodulin administered intravenously circulates in a biologically active form for appreciable time periods

  2. Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress.

    Science.gov (United States)

    Klumpe, Inga; Savvatis, Konstantinos; Westermann, Dirk; Tschöpe, Carsten; Rauch, Ursula; Landmesser, Ulf; Schultheiss, Heinz-Peter; Dörner, Andrea

    2016-06-01

    Ischemia impairs the adenine nucleotide translocase (ANT), which transports ADP and ATP across the inner mitochondrial membrane. We investigated whether ANT1 overexpression has protective effects on ischemic hearts. Myocardial infarction was induced in wild-type (WT) and heart-specific ANT1-transgenic (ANT1-TG) rats, and hypoxia was set in isolated cardiomyocytes. ANT1 overexpression reduced the myocardial infarct area and increased the survival rate of infarcted rats. Reduced ANT1 expression and increased 4-hydroxynonenal modification of ANT paralleled to impaired ANT function in infarcted WT hearts. ANT1 overexpression improved ANT expression and function. This was accompanied by reduced mitochondrial cytochrome C release and caspase-3 activation. ANT1-TG hearts suffered less from oxidative stress, as shown by lower protein carbonylation and 4-hydroxynonenal modification of ANT. ANT1 overexpression also increased cell survival of hypoxic cardiomyocytes and attenuated reactive oxygen species (ROS) production. This was linked to higher stability of mitochondrial membrane potential and lower activity of ROS detoxifying catalase. ANT1-TG cardiomyocytes also showed higher resistance against H2O2 treatment, which was independent of catalase activity. In conclusion, ANT1 overexpression compensates impaired ANT activity under oxygen-restricted conditions. It reduces ROS production and oxidative stress, stabilizes mitochondrial integrity, and increases survival, making ANT1 a component in ROS management and heart protection during ischemia. ANT1 overexpression reduces infarct size and increases survival after infarction. ANT1 overexpression compensates restricted ANT expression and function in infarcted hearts. Increased ANT1 expression enhances mitochondrial integrity. ANT1-overexpressing hearts reduce oxidative stress by decreasing ROS generation. ANT1 is a component in ROS management and heart protection.

  3. The possible protective effects of dipyridamole on ischemic reperfusion injury of priapism

    Directory of Open Access Journals (Sweden)

    Ersagun Karaguzel

    2016-02-01

    Full Text Available ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2, tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p0.05. There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.

  4. Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

    Science.gov (United States)

    Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

    2006-07-01

    The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of signaling molecules, in contributing to protection of cardiac myocytes from ischemic damage.

  5. The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection.

    Science.gov (United States)

    Johnsen, Jacob; Pryds, Kasper; Salman, Rasha; Løfgren, Bo; Kristiansen, Steen Buus; Bøtker, Hans Erik

    2016-03-01

    Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.

  6. Proteasome inhibitors enhance endothelial thrombomodulin expression via induction of Krüppel-like transcription factors

    NARCIS (Netherlands)

    Hiroi, Toyoko; Deming, Clayton B.; Zhao, Haige; Hansen, Baranda S.; Arkenbout, Elisabeth K.; Myers, Thomas J.; McDevitt, Michael A.; Rade, Jeffrey J.

    2009-01-01

    OBJECTIVE: Impairment of the thrombomodulin-protein C anticoagulant pathway has been implicated in pathological thrombosis associated with malignancy. Patients who receive proteasome inhibitors as part of their chemotherapeutic regimen appear to be at decreased risk for thromboembolic events. We

  7. Thrombomodulin Expression in Tissues From Dogs With Systemic Inflammatory Disease.

    Science.gov (United States)

    Kim, S D; Baker, P; DeLay, J; Wood, R D

    2016-07-01

    Thrombomodulin (TM) is a membrane glycoprotein expressed on endothelial cells, which plays a major role in the protein C anticoagulation pathway. In people with inflammation, TM expression can be down-regulated on endothelial cells and a soluble form released into circulation, resulting in increased risk of thrombosis and disseminated intravascular coagulation. TM is present in dogs; however, there has been minimal investigation of its expression in canine tissues, and the effects of inflammation on TM expression in canine tissues have not been investigated. The objective of this study was to evaluate endothelial TM expression in tissues from dogs with systemic inflammatory diseases. A retrospective evaluation of tissue samples of lung, spleen, and liver from dogs with and without systemic inflammatory diseases was performed using immunohistochemistry (IHC) and a modified manual IHC scoring system. TM expression was significantly reduced in all examined tissues in dogs diagnosed with septic peritonitis or acute pancreatitis. © The Author(s) 2016.

  8. Protective effect of remote limb ischemic perconditioning on the liver grafts of rats with a novel model.

    Directory of Open Access Journals (Sweden)

    Junjun Jia

    Full Text Available Remote ischemic conditioning (RIC is a known manual conditioning to decrease ischemic reperfusion injury (IRI but not increase ischemic time. Here we tried to establish a rat RIC model of liver transplantation (LT, optimize the applicable protocols and investigate the protective mechanism.The RIC model was developed by a standard tourniquet. Sprague-Dawley rats were assigned randomly to the sham operated control (N, standard rat liver transplantation (OLT and RIC groups. According to the different protocols, RIC group was divided into 3 subgroups (10 min×3, n = 6; 5 min×3, n = 6; 1 min×3, n = 6 respectively. Serum transaminases (ALT, AST, creatine kinase (CK, histopathologic changes, malondialdehyde (MDA, myeloperoxidase (MPO and expressions of p-Akt were evaluated.Compared with the OLT group, the grafts subjected to RIC 5min*3 algorithm showed significant reduction of morphological damage and improved the graft function. Also, production of reactive oxygen species (MDA and neutrophil accumulation (MPO were markedly depressed and p-Akt was upregulated.In conclusion, we successfully established a novel model of RIC in rat LT, the optimal RIC 5min*3 algorithm seemed to be more efficient to alleviate IRI of the liver graft in both functional and morphological categories, which due to its antioxidative, anti-inflammation activities and activating PI3K Akt pathway.

  9. Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

    Science.gov (United States)

    Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

    2016-05-15

    Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

    Science.gov (United States)

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

    2014-01-29

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.

  11. Protective effects of the angiotensin II ATreceptor agonist compound 21 in ischemic stroke

    DEFF Research Database (Denmark)

    Bennion, Douglas M; Jones, Chad H; Dang, Alex N

    2018-01-01

    ) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2receptor agonists are blood-brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver...... in certain human central nervous system diseases, the N2B application of AT2receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.......-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective...

  12. Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

    Science.gov (United States)

    Hullinger, Thomas G.; Montgomery, Rusty L.; Seto, Anita G.; Dickinson, Brent A.; Semus, Hillary M.; Lynch, Joshua M.; Dalby, Christina M.; Robinson, Kathryn; Stack, Christianna; Latimer, Paul A.; Hare, Joshua M.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Rationale Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. Objective This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Methods and Results Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Conclusions Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID:22052914

  13. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting. Comparison of several anti-embolic protection devices

    International Nuclear Information System (INIS)

    Taha, M.M.; Maeda, Masayuki; Sakaida, Hiroshi

    2009-01-01

    Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm 3 vs. 86.9 mm 3 , respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm 3 ) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm 3 and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions. (author)

  14. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting: Comparison of several anti-embolic protection devices.

    Science.gov (United States)

    Taha, Mahmoud M; Maeda, Masayuki; Sakaida, Hiroshi; Kawaguchi, Kenji; Toma, Naoki; Yamamoto, Akitaka; Hirose, Tomofumi; Miura, Youichi; Fujimoto, Masashi; Matsushima, Satoshi; Taki, Waro

    2009-09-01

    Distal embolism is an important periprocedural technical complication with carotid angioplasty and carotid artery stenting (CAS). We evaluated the safety and efficacy of protection devices used during CAS by detecting new cerebral ischemic lesions using diffusion-weighted magnetic resonance imaging in 95 patients who underwent 98 CAS procedures: 34 using single PercuSurge GuardWire, 31 using double balloon protection, 15 using proximal flow reverse protection devices, 14 using Naviballoon, and 4 using filter anti-embolic devices. Diffusion-weighted imaging was performed preoperatively and postoperatively to evaluate the presence of any new embolic cerebral lesions. Postoperative diffusion-weighted imaging revealed 117 new ischemic lesions. Three patients had new ischemic stroke, two minor and one major, all ipsilateral to the treated carotid artery. The remaining patients had clinically silent ischemia. The incidence of new embolic lesions was lower using the proximal flow reverse protection device than with the double balloon protection (33% vs. 48.4%), but the volume of ipsilateral new ischemic lesions per patient was 136.6 mm(3) vs. 86.9 mm(3), respectively. Neuroprotection with Naviballoon yielded ipsilateral lesions of large volume (86.6 mm(3)) and higher number (5.7 lesions per patient) than using the filter anti-embolic device (34.8 mm(3) and 1 lesion per patient). New cerebral ischemic lesions after neuroprotected CAS are usually silent. The lower incidence of distal ischemia using proximal flow reverse and double balloon protection devices is limited by the larger volume and higher number of ischemic lesions.

  15. Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

    Science.gov (United States)

    Mourouzis, I; Dimopoulos, A; Saranteas, T; Tsinarakis, N; Livadarou, E; Spanou, D; Kokkinos, A D; Xinaris, C; Pantos, C; Cokkinos, D V

    2009-01-01

    There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (Phearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (Phearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

  16. Thrombomodulin and von Willebrand factor as markers of radiation-induced endothelial injury

    International Nuclear Information System (INIS)

    Zhou Quansheng; Zhao Yimin; Li Peixia; Bai Xia; Ruan Changgeng

    1992-02-01

    Cultured confluent human umbilical vein endothelial cells were irradiated in vitro by 60 Co-gamma ray at doses from 0 to 50 Gy. After irradiation Thrombomodulin in the supernatants of endothelial cell culture medium, on the surface of the cells and within the cells was measured at different times over six days. At twenty-four hours after irradiation, an increase in the release of Thrombomodulin and von Willebrand factor from irradiated endothelial cells and an increase in the number of molecules and the activity of Thrombomodulin on the surface of the cells were observed, which were radiation-dose dependent. The capacity of the cells to produce and release Thrombomodulin was decreased from two to six days after exposure to 60 Co-gamma ray. Our data indicate that radiation can injure endothelial cells and that Thrombomodulin may be as a marker of radiation-induced endothelial cell injury. The relationship between dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation sickness are discussed

  17. Measurement of inflammatory cytokines and thrombomodulin in chronic subdural hematoma.

    Science.gov (United States)

    Kitazono, Masatoshi; Yokota, Hiroyuki; Satoh, Hidetaka; Onda, Hidetaka; Matsumoto, Gaku; Fuse, Akira; Teramoto, Akira

    2012-01-01

    Inflammation and the coagulation system may influence the genesis of chronic subdural hematoma (CSDH). The appearance of CSDH on computed tomography (CT) varies with the stage of the hematoma. This study investigated the pathogenesis and the recurrence of CSDH by comparing cytokine levels with the CT features of CSDH in 26 patients with 34 CSDHs who underwent single burr-hole surgery at our hospital between October 2004 and November 2006. The hematoma components removed during the procedure were examined, and the hematoma serum levels of cytokines measured such as thrombomodulin (TM), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and interleukin-10 (IL-10). Using CT, mixed density hematomas were distinguished from other homogeneous hematomas, and found that the TM level was significantly higher in mixed density hematomas than in homogeneous hematomas (p = 0.043). Mixed density hematomas were classified into three subtypes (laminar, separated, and trabecular hematomas). The TM level was significantly higher in laminar and separated hematomas than in other hematomas (p = 0.01). The levels of IL-6, TNFα, and IL-10 were extremely high, but showed no significant differences in relation to the CT features. Mixed density hematomas had high recurrence rate, as reported previously, and TM level was high in mixed density hematomas such as laminar and separated mixed density hematomas. The present findings suggest that the types of CSDH associated with high TM levels tend to have higher recurrence rate.

  18. Effect of certain natural antioxidants in protecting against damage caused by gamma radiation in ischemic rat intestine

    International Nuclear Information System (INIS)

    Hassan, T.A.A.

    2009-01-01

    Oxidative stress plays an important role in various clinical pathologies one of which is ischemia/reperfusion (I/R)- induced injury. Intestinal I/R enhances production of reactive oxygen species (ROS), inflammatory mediators and induces apoptosis. In other hand. the intestinal tract shows a high sensitivity to ionizing radiation due to a rapid cell turnover and is often implicated in radiation sickness the radiation damage may either be a consequence of a direct effect resulting in disruption of critical molecule (such as an enzyme or DNA) or an indirect effect through ionization of water molecules and formation of ROS. consequently, supplementation of antioxidants may be a beneficial approach to protect against cellular damages associated with oxidative stress. the current study was aimed to evaluate the possible protective effects of vitamin E (100 mg/kg p.o.), tomato extract (67 mg/kg. p.o.) and turmeric (100 mg/kg, p.o) against ileal injury induced in rats by total occlusion of the superior mesenteric artery for 30 min followed by reperfusion for another 30 min. Furthermore, this protective effect of the mentioned drugs was extended into injury that could happened in ileal tissues of rats exposed to (6 Gy) gamma radiation followed by intestinal I/R. Drugs were administered one daily for 14 consecutive days prior to the ischemic insult. Damage induced by I/R was manifested by depletion of ileal content of reduced glutathion (GSH) as well as Lactate dehydrogenas (LDH) activity, associated with elevation of ileal contents of thiobarbituric acid reactive substances (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Intestinal ischemic insults were exacerbated by radiation injury on comparing different untreated controls; except the ileal content of GSH which has elevated due to the preconditioning effect of irradiation. Vitamin E provided a significant protection against the decrease in LDH activity as well as the increase in TBARS

  19. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

    Directory of Open Access Journals (Sweden)

    Yao-xian Xiang

    2015-01-01

    Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

  20. DELETION OR INHIBITION OF THE OXYGEN SENSOR PHD1 PROTECTS AGAINST ISCHEMIC STROKE VIA REPROGRAMMING OF NEURONAL METABOLISM

    Science.gov (United States)

    Quaegebeur, Annelies; Segura, Inmaculada; Schmieder, Roberta; Verdegem, Dries; Decimo, Ilaria; Bifari, Francesco; Dresselaers, Tom; Eelen, Guy; Ghosh, Debapriva; Schoors, Sandra; Janaki Raman, Sudha Rani; Cruys, Bert; Govaerts, Kristof; De Legher, Carla; Bouché, Ann; Schoonjans, Luc; Ramer, Matt S.; Hung, Gene; Bossaert, Goele; Cleveland, Don W.; Himmelreich, Uwe; Voets, Thomas; Lemmens, Robin; Bennett, C. Frank; Robberecht, Wim; De Bock, Katrien; Dewerchin, Mieke; Fendt, Sarah-Maria; Ghesquière, Bart; Carmeliet, Peter

    2016-01-01

    Summary The oxygen-sensing prolyl hydroxylase domain proteins (PHDs) regulate cellular metabolism, but their role in neuronal metabolism during stroke is unknown. Here we report that PHD1 deficiency provides neuroprotection in a murine model of permanent brain ischemia. This was not due to an increased collateral vessel network, nor to enhanced neurotrophin expression. Instead, PHD1−/− neurons were protected against oxygen-nutrient deprivation by reprogramming glucose metabolism. Indeed, PHD1−/− neurons enhanced glucose flux through the oxidative pentose phosphate pathway by diverting glucose from glycolysis. As a result, PHD1−/− neurons increased their redox buffering capacity to scavenge oxygen radicals in ischemia. Intracerebroventricular injection of PHD1-antisense oligonucleotides reduced the cerebral infarct size and neurological deficits following stroke. These data identify PHD1 as a novel regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke. PMID:26774962

  1. Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism.

    Science.gov (United States)

    Quaegebeur, Annelies; Segura, Inmaculada; Schmieder, Roberta; Verdegem, Dries; Decimo, Ilaria; Bifari, Francesco; Dresselaers, Tom; Eelen, Guy; Ghosh, Debapriva; Davidson, Shawn M; Schoors, Sandra; Broekaert, Dorien; Cruys, Bert; Govaerts, Kristof; De Legher, Carla; Bouché, Ann; Schoonjans, Luc; Ramer, Matt S; Hung, Gene; Bossaert, Goele; Cleveland, Don W; Himmelreich, Uwe; Voets, Thomas; Lemmens, Robin; Bennett, C Frank; Robberecht, Wim; De Bock, Katrien; Dewerchin, Mieke; Ghesquière, Bart; Fendt, Sarah-Maria; Carmeliet, Peter

    2016-02-09

    The oxygen-sensing prolyl hydroxylase domain proteins (PHDs) regulate cellular metabolism, but their role in neuronal metabolism during stroke is unknown. Here we report that PHD1 deficiency provides neuroprotection in a murine model of permanent brain ischemia. This was not due to an increased collateral vessel network. Instead, PHD1(-/-) neurons were protected against oxygen-nutrient deprivation by reprogramming glucose metabolism. Indeed, PHD1(-/-) neurons enhanced glucose flux through the oxidative pentose phosphate pathway by diverting glucose away from glycolysis. As a result, PHD1(-/-) neurons increased their redox buffering capacity to scavenge oxygen radicals in ischemia. Intracerebroventricular injection of PHD1-antisense oligonucleotides reduced the cerebral infarct size and neurological deficits following stroke. These data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Protection of Ischemic and Reperfused Rat Heart by Aqueous Extract of Urtica Dioica

    Directory of Open Access Journals (Sweden)

    D Shackebaei

    2010-09-01

    Full Text Available Background: Urtica dioica (U.D has widely been used in traditional medicine for its hypotensive and vasodilatory effects. The objective of this study was to clarify the effects of aqueous extract of Urtica dioica on isolated ischemia- reperfused heart.Methods: The heart of male wistar rats were isolated and perfused according to langendorff method. In the control group (n = 13 the hearts were subjected to three steps of stabilization (30 min, normothermic global ischemia (40 min and reperfusion (45 min. In addition, before and after ischemia, the aqueous extract of U.D (200 mg/ml was added to perfusion solution in the test group (n=14. Different cardiac variables including left ventricular pressure, heart rate and coronary flow were measured and rate pressure product was calculated.Results: Results showed that left ventricular pressure (59.11±4.7 and rate pressure product (13680±1136 in 45th minute of reperfusion in the test group were significantly (P=0.0187 and 0.0321 respectively greater than the control group (39.1±6.0, 9480±1480 respectively. These findings indicated decreased cardiac damage following ischemia in the test group, compared with that of control group.Conclusion: Results of the present study showed that the aqueous extract of U.D, increased the tolerance of isolated rat hearts against ischemic damage. This effect can be explained by potent antioxidant activity of the U.D extract, suggesting its clinical use in ischemic heart disease.

  3. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

    Science.gov (United States)

    Park-Hansen, Jesper; Holme, Susanne J V; Irmukhamedov, Akhmadjon; Carranza, Christian L; Greve, Anders M; Al-Farra, Gina; Riis, Robert G C; Nilsson, Brian; Clausen, Johan S R; Nørskov, Anne S; Kruuse, Christina R; Rostrup, Egill; Dominguez, Helena

    2018-05-23

    Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

  4. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

    Science.gov (United States)

    Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

    2015-07-01

    Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

  5. (1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

    Science.gov (United States)

    Luo, Lan; Zhen, Lifeng; Xu, Yatao; Yang, Yongxia; Feng, Suxiang; Wang, Shumei; Liang, Shengwang

    2016-06-20

    Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

  7. Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke.

    Science.gov (United States)

    Gelderblom, Mathias; Weymar, Anna; Bernreuther, Christian; Velden, Joachim; Arunachalam, Priyadharshini; Steinbach, Karin; Orthey, Ellen; Arumugam, Thiruma V; Leypoldt, Frank; Simova, Olga; Thom, Vivien; Friese, Manuel A; Prinz, Immo; Hölscher, Christoph; Glatzel, Markus; Korn, Thomas; Gerloff, Christian; Tolosa, Eva; Magnus, Tim

    2012-11-01

    The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell-dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4(+) T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A-blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A-positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.

  8. Protection of Liver as a Remote Organ after Renal Ischemia-Reperfusion Injury by Renal Ischemic Postconditioning

    Directory of Open Access Journals (Sweden)

    Behjat Seifi

    2014-01-01

    Full Text Available This study was designed to investigate the protective effects of local renal ischemic postconditioning (POC on liver damage after renal ischemia-reperfusion (IR injury. Male rats were divided into three groups  (n=8. They underwent a right nephrectomy before induction of 45 minutes of left kidney ischemia or sham operation. POC was performed by four cycles of 10 seconds of ischemia and 10 seconds of reperfusion just at the beginning of 24 hours of reperfusion. Then blood and liver samples were collected to measure serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and liver oxidative stress parameters including superoxide dismutase (SOD activity and malondialdehyde (MDA level. Renal IR caused a significant increase in liver functional indices as demonstrated by increased serum AST and ALT compared to sham group. These parameters reduced significantly in POC group compared to IR group. Liver MDA levels increased and SOD activity decreased in IR group compared to sham group. Induction of POC reduced the elevated liver MDA levels and increased the reduced liver SOD activity. These results revealed that renal IR injury causes liver damage as a remote organ and POC protects liver from renal IR injury by a modification in the hepatic oxidative stress status.

  9. Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement.

    Science.gov (United States)

    Ushida, Yuka; Koshy, Geena; Kawashima, Yoko; Kiji, Makoto; Umeda, Makoto; Nitta, Hiroshi; Nagasawa, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

    2008-11-01

    This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.

  10. Soluble thrombomodulin levels in plasma of multiple sclerosis patients and their implication.

    Science.gov (United States)

    Festoff, Barry W; Li, Chaoyang; Woodhams, Barry; Lynch, Sharon

    2012-12-15

    Thrombomodulin (TM) on the cell-surface of cerebrovascular endothelial cells (CECs) is released into blood upon CEC damage. TM promotes activation of protein C (APC), an anticoagulant, anti-inflammatory, neuroprotective molecule that protects CECs and impedes inflammatory cell migration across the blood-brain barrier (BBB). Multiple sclerosis (MS) is associated with CEC damage and BBB dysfunction. We evaluated soluble TM (sTM) levels as a biomarker of BBB integrity and whether glatiramer acetate (GA) influenced sTM levels in MS patients. sTM levels quantified by 2-site ELISA from sera of healthy controls and systemic lupus erythematosus (SLE) patients (CEC-damage positive control) were compared with levels from patients with relapsing-remitting (RRMS) or secondary-progressive MS (SPMS), stratified as: RRMS/GA/no relapse, RRMS/GA/in relapse, RRMS no GA/no relapse, RRMS/no GA/in relapse; and SPMS/no GA. Additionally, soluble endothelial protein C receptor (sEPCR) levels were assessed in the non-stratified MS group, SLE patients, and controls. sTM levels were highest in RRMS patients taking GA with or without relapse, followed in decreasing order by SLE, RRMS/no GA/in relapse, SPMS, RRMS/no GA/no relapse, healthy controls. sEPCR levels were highest in MS patients, then SLE, then controls. sTM may be a useful biomarker of BBB integrity in RRMS patients. Further evaluation of sEPCR is needed. The finding that the highest sTM levels were in RRMS patients taking GA is interesting and warrants further investigation. Published by Elsevier B.V.

  11. P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

    NARCIS (Netherlands)

    Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

    2007-01-01

    The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

  12. Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2/Bax expression.

    Science.gov (United States)

    Liu, Qing-Shan; Deng, Ran; Li, Shuran; Li, Xu; Li, Keqin; Kebaituli, Gulibanumu; Li, Xueli; Liu, Rui

    2017-08-01

    An oxygen-glucose deprivation and reoxygenation model in primary cultured rat cortical neurons was developed for this study to investigate the effects of ellagic acid (EA), a low-molecular-weight polyphenol, on neuron cells and their function, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent. Administration of EA significantly decreased the volume of cerebrum infarction and the neurological deficit scores of the rats; EA treatment also increased the number of Bcl-2-positive cells and the ratio of Bcl-2-positive to Bax-positive neurons in the semidarkness zone near the brain ischemic focus in the photothrombotic cerebral ischemia model. Treatment of EA resulted in increased neuron viability, cell nuclear integrity, and the ratio of Bcl-2/Bax expression in the primary cultured neuron model; EA treatment also lead to a decrease in the number of apoptotic cells. Our results therefore suggest a specific mechanism for the beneficial effects of EA, providing new insights into how it provides neuroprotection. To the best of our knowledge, these results represent new insights on the mechanisms of the brain cell protective activity of EA. Thus, EA may be used in functional foods or medicines to help treat nerve dysfunction, neurodegenerative disease, and aging.

  13. Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

    Science.gov (United States)

    Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

    2017-04-03

    Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Brevoord, Daniel; Kranke, Peter; Kuijpers, Marijn; Weber, Nina; Hollmann, Markus; Preckel, Benedikt

    2012-01-01

    Background Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference −0.28 [−0.47, −0.09]). Conclusion There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin. PMID:22860077

  15. Protective Effect of Klotho against Ischemic Brain Injury Is Associated with Inhibition of RIG-I/NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Hong-Jing Zhou

    2018-01-01

    Full Text Available Aging is the greatest independent risk factor for the occurrence of stroke and poor outcomes, at least partially through progressive increases in oxidative stress and inflammation with advanced age. Klotho is an antiaging gene, the expression of which declines with age. Klotho may protect against neuronal oxidative damage that is induced by glutamate. The present study investigated the effects of Klotho overexpression and knockdown by an intracerebroventricular injection of a lentiviral vector that encoded murine Klotho (LV-KL or rat Klotho short-hairpin RNA (LV-KL shRNA on cerebral ischemia injury and the underlying anti-neuroinflammatory mechanism. The overexpression of Klotho induced by LV-KL significantly improved neurobehavioral deficits and increased the number of live neurons in the hippocampal CA1 and caudate putamen subregions 72 h after cerebral hypoperfusion that was induced by transient bilateral common carotid artery occlusion (2VO in mice. The overexpression of Klotho significantly decreased the immunoreactivity of glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1, the expression of retinoic-acid-inducible gene-I, the nuclear translocation of nuclear factor-κB, and the production of proinflammatory cytokines (tumor necrosis factor α and interleukin-6 in 2VO mice. The knockdown of Klotho mediated by LV-KL shRNA in the brain exacerbated neurological dysfunction and cerebral infarct after 22 h of reperfusion following 2 h middle cerebral artery occlusion in rats. These findings suggest that Klotho itself or enhancers of Klotho may compensate for its aging-related decline, thus providing a promising therapeutic approach for acute ischemic stroke during advanced age.

  16. The relation of thrombomodulin G33A and C1418T gene ...

    African Journals Online (AJOL)

    Wael Alkhiary

    2017-08-31

    Aug 31, 2017 ... Aim of the study: To assess whether Thrombomodulin (TM) G33A and C1418T gene polymorphisms are related to the .... the AA genotype (24 and 235 bp). The wild-type G .... in two meta-analyses of a total of 13 and 14 case-control studies, ... Diabetic. 41 (37.3%). 39 (38.2%). NS. Non Diabetic. 69 (62.7%).

  17. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    OpenAIRE

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-01-01

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate isch...

  18. Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

    Science.gov (United States)

    Bai, Xue; Zhang, Xiangjian; Chen, Linyu; Zhang, Jian; Zhang, Lan; Zhao, Xumeng; Zhao, Ting; Zhao, Yuan

    2014-08-01

    Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

  19. Retinal protective effects of topically administered agmatine on ischemic ocular injury caused by transient occlusion of the ophthalmic artery

    Directory of Open Access Journals (Sweden)

    S. Hong

    2012-03-01

    Full Text Available Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6, a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6, a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL. Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P < 0.001; Kruskal-Wallis test. Overall, we determined that topical agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases.

  20. Retinal protective effects of topically administered agmatine on ischemic ocular injury caused by transient occlusion of the ophthalmic artery

    Science.gov (United States)

    Hong, S.; Hara, H.; Shimazawa, M.; Hyakkoku, K.; Kim, C.Y.; Seong, G.J.

    2012-01-01

    Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g) for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6), a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6), a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases. PMID:22331138

  1. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, Eiji [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Takagi, Yoshimi [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Honda, Goichi [Medical Affairs Department, Asahi Kasei Pharma Corporation, 1-105 Kanda Jinbo-cho, Chiyoda-ku, Tokyo 101-8101 (Japan); Suzuki, Koji [Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679 (Japan); Imai, Hiroshi [Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Shimaoka, Motomu, E-mail: shimaoka@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan)

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.

  2. Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

    Directory of Open Access Journals (Sweden)

    En-ping Jiang

    2011-06-01

    Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

  3. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation

    International Nuclear Information System (INIS)

    Kim, Dae-Seok; Kim, Bora; Tahk, Hongmin; Kim, Dong-Hyun; Ahn, Eu-Ree; Choi, Changsun; Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun; Kim, Soo-Youl

    2010-01-01

    Research highlights: → No acute renal tubular necrotic lesions were found in TGase2 -/- mice with ischemic kidney injury. → NF-κB activation is reduced in TGase2 -/- mice with ischemic kidney injury. → Hypoxic stress did not increase NF-κB activity in MEFs from TGase2 -/- mice. → COX-2 induction is suppressed in TGase2 -/- mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2 -/- ) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-κB (NF-κB) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-κB activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-κB activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-κB activity in mouse embryogenic fibroblasts (MEFs) from TGase2 -/- mice remained at the control level while the NF-κB activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-κB activity remained at the control level in TGase2 -/- mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-κB activation in ischemic injury.

  4. Analysis of CD45- [CD34+/KDR+] endothelial progenitor cells as juvenile protective factors in a rat model of ischemic-hemorrhagic stroke.

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    Julius L Decano

    Full Text Available Identification of juvenile protective factors (JPFs which are altered with age and contribute to adult-onset diseases could identify novel pathways for reversing the effects of age, an accepted non-modifiable risk factor to adult-onset diseases. Since endothelial progenitor cells (EPCs have been observed to be altered in stroke, hypertension and hypercholesterolemia, said EPCs are candidate JPFs for adult-onset stroke. A priori, if EPC aging plays a 'master-switch JPF-role' in stroke pathogenesis, juvenile EPC therapy alone should delay stroke-onset. Using a hypertensive, transgenic-hyperlipidemic rat model of spontaneous ischemic-hemorrhagic stroke, spTg25, we tested the hypothesis that freshly isolated juvenile EPCs are JPFs that can attenuate stroke progression and delay stroke onset.FACS analysis revealed that CD45- [CD34+/KDR+] EPCs decrease with progression to stroke in spTg25 rats, exhibit differential expression of the dual endodthelin-1/VEGFsp receptor (DEspR and undergo differential DEspR-subtype specific changes in number and in vitro angiogenic tube-incorporation. In vivo EPC infusion of male, juvenile non-expanded cd45-[CD34+/KDR+] EPCs into female stroke-prone rats prior to stroke attenuated progression and delayed stroke onset (P<0.003. Detection of Y-chromosome DNA in brain microvessels of EPC-treated female spTg25 rats indicates integration of male EPCs into female rat brain microvessels. Gradient-echo MRI showed delay of ischemic-hemorrhagic lesions in EPC-treated rats. Real-time RT-PCR pathway-specific array-analysis revealed age-associated gene expression changes in CD45-[CD34+/KDR]EPC subtypes, which were accelerated in stroke-prone rats. Pro-angiogenic genes implicated in intimal hyperplasia were increased in stroke-prone rat EPCs (P<0.0001, suggesting a maladaptive endothelial repair system which acts like a double-edged sword repairing while predisposing to age-associated intimal hyperplasia.Altogether, the data

  5. A novel strategy for hemolytic uremic syndrome: successful treatment with thrombomodulin α.

    Science.gov (United States)

    Honda, Takashi; Ogata, Shohei; Mineo, Eri; Nagamori, Yukako; Nakamura, Shinya; Bando, Yuki; Ishii, Masahiro

    2013-03-01

    Hemolytic uremic syndrome (HUS) is a life-threatening infectious disease in childhood for which there is no confirmed therapeutic strategy. Endothelial inflammation leading to microthrombosis formation via complement activation is the main pathology of HUS. Thrombomodulin is an endothelial membrane protein that has anticoagulation and anti-inflammatory effects, including the suppression of complement activity. Recombinant human soluble thrombomodulin (rTM) is a novel therapeutic medicine for disseminated intravascular coagulation. We administered rTM to 3 patients with HUS for 7 days and investigated the outcomes in view of the patients' prognoses, changes in biochemical markers, complications, and adverse effects of rTM. Symptoms and laboratory data improved after initiation of rTM in all 3 patients. Abnormal activation of complements was also dramatically suppressed in 1 patient. The patients recovered without any complications or adverse effects of rTM. They were discharged having normal neurologic status and with no renal dysfunction. To our knowledge, this is the first report of rTM being used to treat HUS. These case reports show the positive effect of rTM in patients with HUS. Randomized controlled studies should be performed to assess the efficacy and safety of rTM for children with HUS.

  6. Dynamin-Related Protein 1 Inhibitors Protect against Ischemic Toxicity through Attenuating Mitochondrial Ca2+ Uptake from Endoplasmic Reticulum Store in PC12 Cells

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    Ye Tian

    2014-02-01

    Full Text Available Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1, in neuronal injury induced by oxygen-glucose deprivation (OGD in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP. Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca2+ uptake, but had no effect on cytoplasmic Ca2+ after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER Ca2+ release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca2+ uptake from the ER store and attenuating mitochondrial dysfunction.

  7. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

    NARCIS (Netherlands)

    Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

  8. Thrombomodulin Is Silenced in Malignant Mesothelioma by a Poly(ADP-ribose) Polymerase-1-mediated Epigenetic Mechanism

    Czech Academy of Sciences Publication Activity Database

    Nocchi, L.; Tomasetti, M.; Amati, M.; Neužil, Jiří; Santarelli, L.; Saccucci, F.

    2011-01-01

    Roč. 286, č. 22 (2011), s. 19478-19488 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Thrombomodulin gene promoter * malignant mesothelioma * poly(ADP-ribose) polymerase-1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.773, year: 2011

  9. Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

    DEFF Research Database (Denmark)

    Liu, Dong; Croteau, Deborah L; Souza-Pinto, Nadja

    2011-01-01

    to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential......7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons....... Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA...

  10. The effect of cigarette smoke extract on thrombomodulin-thrombin binding: an atomic force microscopy study.

    Science.gov (United States)

    Wei, Yujie; Zhang, Xuejie; Xu, Li; Yi, Shaoqiong; Li, Yi; Fang, Xiaohong; Liu, Huiliang

    2012-10-01

    Cigarette smoking is a well-known risk factor for cardiovascular disease. Smoking can cause vascular endothelial dysfunction and consequently trigger haemostatic activation and thrombosis. However, the mechanism of how smoking promotes thrombosis is not fully understood. Thrombosis is associated with the imbalance of the coagulant system due to endothelial dysfunction. As a vital anticoagulation cofactor, thrombomodulin (TM) located on the endothelial cell surface is able to regulate intravascular coagulation by binding to thrombin, and the binding results in thrombosis inhibition. This work focused on the effects of cigarette smoke extract (CSE) on TM-thrombin binding by atomic force microscopy (AFM) based single-molecule force spectroscopy. The results from both in vitro and live-cell experiments indicated that CSE could notably reduce the binding probability of TM and thrombin. This study provided a new approach and new evidence for studying the mechanism of thrombosis triggered by cigarette smoking.

  11. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension.

    Science.gov (United States)

    Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

    2004-01-01

    Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Cross-sectional study of 36 consecutive women with PIH (age 31+/-6 years) and 36 consecutive women with normotensive pregnancies (age 29+/-5 years) of similar parity. Plasma levels of vWf, E-selectin and thrombomodulin were measured using ELISA. As expected, women with PIH had significantly higher levels of plasma vWf (by 19%, p=0.003), E-selectin (by 40%, p<0.001) and thrombomodulin (by 61%, p=0.01) than normotensive women. However, on stepwise multiple regression analysis, only thrombomodulin was an independent significant predictor of the presence of PIH (p=0.023). We conclude that although vWf, E-selectin and thrombomodulin are all raised in PIH, only thrombomodulin was independently associated with PIH. This molecule could potentially be useful in monitoring and in providing clues in aetiology and pathophysiology, and may have implications for the clinical complications associated with PIH.

  12. Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Maruyama, I.; Majerus, P.W.

    1987-01-01

    We investigated the effect of protein C on the endocytosis of thrombin-thrombomodulin complexes. We previously showed that exposure of umbilical vein endothelial cells to thrombin stimulated the internalization and degradation of thrombin. A similar internalization was stimulated by a monoclonal antithrombomodulin antibody. We have repeated these studies in the presence of protein C and found that endocytosis of 125 I-thrombin-thrombomodulin complexes, but not 125 I-antithrombomodulin-thrombomodulin complexes, is inhibited. Activated protein C did not inhibit endocytosis of thrombin-thrombomodulin complexes. Protein C inhibited both internalization and degradation of 125 I-thrombin and diisopropylphosphoryl (DIP) 125 I-thrombin in human lung cancer cells (A549). These effects were observed at protein C concentrations found in human plasma. Protein S had no effect on the inhibition of endocytosis of thrombin-thrombomodulin complexes by protein C. We propose that protein C may regulate the rate of endocytosis of thrombin-thrombomodulin complexes in vivo and thereby control the capacity for endothelium to activate protein C

  13. Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

    Science.gov (United States)

    Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

    2017-08-15

    Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all Pfatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  14. Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Dongsun Park

    2015-01-01

    Full Text Available Objective. Since oligodendrocyte progenitor cells (OPCs are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE, the present study was aimed at investigating the protective effects of N-acetyl-L-cysteine (NAC, a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

  15. No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

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    Nilgün Gedik

    Full Text Available Remote ischemic preconditioning (RIPC by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG. Activation of signal transducer and activator of transcription 5 (STAT5 in left ventricular (LV myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation or placebo (cuff deflated before skin incision (n = 10/10. Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline and at early (5-10 min reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002. Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12 complex, light chain 3 (LC3, parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02. STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05.Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

  16. Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

    Science.gov (United States)

    Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

    2013-07-01

    Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (Pregional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier

  17. Heme oxygenase-1 mediates the protective effects of ischemic preconditioning on mitigating lung injury induced by lower limb ischemia-reperfusion in rats.

    Science.gov (United States)

    Peng, Tsui-Chin; Jan, Woan-Ching; Tsai, Pei-Shan; Huang, Chun-Jen

    2011-05-15

    Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1). Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined. Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E(2) concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP. The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 against Neuronal Death Caused by Ischemic Insults

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    Tianfei Luo

    2014-09-01

    Full Text Available Lethal autophagy is a pathway leading to neuronal death caused by transient global ischemia. In this study, we examined the effect of Ginsenoside Rb1 (GRb1 on ischemia/reperfusion-induced autophagic neuronal death and investigated the role of PI3K/Akt. Ischemic neuronal death in vitro was induced by using oxygen glucose deprivation (OGD in SH-SY5Y cells, and transient global ischemia was produced by using two vessels occlusion in rats. Cellular viability of SH-SY5Y cells was assessed by MTT assay, and CA1 neuronal death was evaluated by Hematoxylin-eosin staining. Autophagic vacuoles were detected by using both fluorescent microscopy in combination with acridine orange (AO and Monodansylcadaverine (MDC staining and transmission electronic microscopy. Protein levels of LC3II, Beclin1, total Akt and phosphor-Akt at Ser473 were examined by western blotting analysis. GRb1 inhibited both OGD and transient ischemia-induced neuronal death and mitigated OGD-induced autophagic vacuoles in SH-SY5Y cells. By contrast, PI3K inhibitor LY294002 counteracted the protection of GRb1 against neuronal death caused by either OGD or transient ischemia. LY294002 not only mitigated the up-regulated protein level of phosphor Akt at Ser473 caused by GRb1, but also reversed the inhibitory effect of GRb1 on OGD and transient ischemia-induced elevation in protein levels of LC3II and Beclin1.

  19. The Contribution of Different Components in QiShenYiQi Pills® to Its Potential to Modulate Energy Metabolism in Protection of Ischemic Myocardial Injury

    Directory of Open Access Journals (Sweden)

    Yuan-Chen Cui

    2018-04-01

    Full Text Available Ischemic heart diseases remain a challenge for clinicians. QiShenYiQi pills® (QSYQ has been reported to be curative during coronary heart diseases with modulation of energy metabolism as one of the underlying mechanisms. In this study, we detected the effect of QSYQ and its components on rat myocardial structure, mitochondrial respiratory chain complexes activity and energy metabolism, and heart function after 30 min of cardiac ischemia, with focusing on the contribution of each component to its potential to regulate energy metabolism. Results showed that treatment with QSYQ and all its five components protected myocardial structure from damage by ischemia. QSYQ also attenuated release of myocardial cTnI, and restored the production of ATP after cardiac ischemia. AS-IV and Rb1, but not Rg1, R1, and DLA, had similar effect as QSYQ in regulation of energy metabolism. These results indicate that QSYQ may prevent ischemia-induced cardiac injury via regulation of energy metabolism, to which each of its components contributes differently.

  20. Combination therapy with sivelestat and recombinant human soluble thrombomodulin for ARDS and DIC patients

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2014-09-01

    Full Text Available Seigo Miyoshi,1 Ryoji Ito,1 Hitoshi Katayama,1 Kentaro Dote,2 Mayuki Aibiki,3 Hironobu Hamada,1,4 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, 2Intensive Care Division, Ehime University Hospital, 3Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 4Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan Background: Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS and disseminated intravascular coagulation (DIC. However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM for patients with ARDS and DIC remains unknown. Methods: We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment, sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC. Results: Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC

  1. [Study of serum thrombomodulin(TM) levels in patients with hyper- or hypo- thyroidism].

    Science.gov (United States)

    Soma, M; Maeda, Y; Matsuura, R; Sasaki, I; Kasakura, S; Saeki, Y; Ikekubo, K; Ishihara, T; Kurahachi, H; Sasaki, S; Tagami, T; Nakao, K

    1997-01-01

    We studies a relationship between the serum levels of thrombomodulin(TM) and the thyroid functions. Serum TM levels were measured in 48 patients with Graves' disease, 17 patients with primary hypothyroidism, 7 patients with subacute thyroiditis, 5 patients with painless thyroiditis and 2 patients with systematic Refetoff syndrome. These patients did not have malignant tumor, kidney failure, or blood vessel injury. Control sera were obtained from 42 healthy subjects. Serum levels of TM in patients with untreated Graves' disease were significantly higher(p thyroid function(FT3, FT4 and TH) in patients with Graves' disease during treatment showed that both the serum levels of TM and thyroid hormones (FT3 and FT4) lowered progressively during treatment. After normalization of serum FT3 and FT4, the serum TM levels returned to normal. However, the serum levels of TM in patients with destructive thyroiditis and Refetoff syndrome were normal in spite of high serum levels of thyroid hormones. These data suggest that an increase in serum levels of TM is not the direct result of thyroid hormones themselves but is the result of the prolonged hypermetabolic state induced by their peripheral activities. Thyroid hormones may stimulate the synthesis or metabolism of TM on the surface of vascular endothelial cells in the patients with Graves' disease.

  2. End-Point Immobilization of Recombinant Thrombomodulin via Sortase-Mediated Ligation

    Science.gov (United States)

    Jiang, Rui; Weingart, Jacob; Zhang, Hailong; Ma, Yong; Sun, Xue-Long

    2012-01-01

    We report an enzymatic end-point modification and immobilization of recombinant human thrombomodulin (TM), a cofactor for activation of anticoagulant protein C pathway via thrombin. First, a truncated TM mutant consisting of epidermal growth factor-like domains 4–6 (TM456) with a conserved pentapeptide LPETG motif at its C-terminal was expressed and purified in E. coli. Next, the truncated TM456 derivative was site-specifically modified with N-terminal diglycine containing molecules such as biotin and the fluorescent probe dansyl via sortase A (SrtA) mediated ligation (SML). The successful ligations were confirmed by SDS-PAGE and fluorescence imaging. Finally, the truncated TM456 was immobilized onto N-terminal diglycine-functionalized glass slide surface via SML directly. Alternatively, the truncated TM456 was biotinylated via SML and then immobilized onto streptavidin-functionalized glass slide surface indirectly. The successful immobilizations were confirmed by fluorescence imaging. The bioactivity of the immobilized truncated TM456 was further confirmed by protein C activation assay, in which enhanced activation of protein C by immobilized recombinant TM was observed. The sortase A-catalyzed surface ligation took place under mild conditions and is rapid occurring in a single step without prior chemical modification of the target protein. This site-specific covalent modification leads to molecules being arranged in a definitively ordered fashion and facilitating the preservation of the protein’s biological activity. PMID:22372933

  3. Amino acid sequence surrounding the chondroitin sulfate attachment site of thrombomodulin regulates chondroitin polymerization.

    Science.gov (United States)

    Izumikawa, Tomomi; Kitagawa, Hiroshi

    2015-05-01

    Thrombomodulin (TM) is a cell-surface glycoprotein and a critical mediator of endothelial anticoagulant function. TM exists as both a chondroitin sulfate (CS) proteoglycan (PG) form and a non-PG form lacking a CS chain (α-TM); therefore, TM can be described as a part-time PG. Previously, we reported that α-TM bears an immature, truncated linkage tetrasaccharide structure (GlcAβ1-3Galβ1-3Galβ1-4Xyl). However, the biosynthetic mechanism to generate part-time PGs remains unclear. In this study, we used several mutants to demonstrate that the amino acid sequence surrounding the CS attachment site influences the efficiency of chondroitin polymerization. In particular, the presence of acidic residues surrounding the CS attachment site was indispensable for the elongation of CS. In addition, mutants defective in CS elongation did not exhibit anti-coagulant activity, as in the case with α-TM. Together, these data support a model for CS chain assembly in which specific core protein determinants are recognized by a key biosynthetic enzyme involved in chondroitin polymerization. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells

    International Nuclear Information System (INIS)

    Wu Hualin; Lin ChiIou; Huang Yuanli; Chen, Pin-Shern; Kuo, Cheng-Hsiang; Chen, Mei-Shing; Wu, G.C.-C.; Shi, G.-Y.; Yang, H.-Y.; Lee Hsinyu

    2008-01-01

    Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation

  5. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Han-Bin Lin

    2014-01-01

    Full Text Available Matrix metalloproteinases (MMPs significantly contribute to ischemia reperfusion (I/R injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2 in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

  6. Remote Ischemic Conditioning

    Science.gov (United States)

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  7. Edaravone with and without .6 Mg/Kg Alteplase within 4.5 Hours after Ischemic Stroke: A Prospective Cohort Study (PROTECT4.5).

    Science.gov (United States)

    Yamaguchi, Takenori; Awano, Hideto; Matsuda, Hiroaki; Tanahashi, Norio

    2017-04-01

    Edaravone is widely used to treat acute ischemic stroke (AIS) within 24 hours of onset. We aimed to evaluate current edaravone treatment practices and the efficacy and safety of edaravone used with recombinant tissue plasminogen activator (tPA) in AIS patients within 4.5 hours of onset. The results were compared with those of the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) study. PROTECT4.5 was a prospective observational study conducted from April 2010 to March 2013 in Japan. The primary end points were favorable outcomes (modified Rankin Scale score [mRS] 0-1) at 3 months after onset and incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours of treatment. For comparison with SITS-ISTR, patients were categorized based on the time from onset to treatment (within 3 hours of and 3-4.5 hours after onset) and baseline National Institutes of Health Stroke Scale score (NIHSS). Among the 11,384 registered patients, 11,126 and 8274 patients were included in the safety and efficacy analysis populations, respectively. The proportions of patients with mRS 0-1 receiving edaravone alone and edaravone + tPA were 51.3% (95% confidence interval, 49.7%-52.8%) and 39.0% (37.6%-40.5%), respectively. The incidence of sICH within 36 hours after tPA treatment (edaravone + tPA group) was 1.6% (1.3%-2.0%). When compared with the SITS-ISTR results, those treated with edaravone + tPA appeared to show better outcomes in patients with NIHSS score ≥16. The efficacy and safety of edaravone combined with tPA and administered within 4.5 hours of AIS onset were demonstrated with numerically lower incidence of sICH and better outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

    Science.gov (United States)

    Huang, Tzu-Lun; Huang, Shun-Ping; Chang, Chung-Hsing; Lin, Kung-Hung; Chang, Shu-Wen; Tsai, Rong-Kung

    2015-02-01

    This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.

    Science.gov (United States)

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-11-01

    Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability. Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Synthesis of an endothelial cell mimicking surface containing thrombomodulin and endothelial protein C receptor

    Science.gov (United States)

    Kador, Karl Erich

    Synthetic materials for use in blood contacting applications have been studied for many years with limited success. One of the main areas of need for these materials is the design of synthetic vascular grafts for use in the hundreds of thousands of patients who have coronary artery bypass grafting, many without suitable veins for autologous grafts. The design of these grafts is constrained by two common modes of failure, the formation of intimal hyperplasia (IH) and thrombosis. IH formation has been previously linked to a mismatching of the mechanical properties of the graft and has been overcome by creating grafts using materials whose compliance mimics that of the native artery. Several techniques and surface modification have been designed to limit thrombosis on the surface of synthetic materials. One which has shown the greatest promise is the immobilization of Thrombomodulin (TM), a protein found on the endothelial cell membrane lining native blood vessels involved in the activation of the anticoagulant Protein C (PC). While TM immobilization has been shown to arrest thrombin formation and limit fibrous formations in in-vitro and in-vivo experiments, it has shown to be transport limiting under arterial flow. On the endothelial cell surface, TM is co-localized with Endothelial Protein C Receptor (EPCR), which increases PC transport onto the cell surface and increases PC activation via TM between 20-100 fold. This dissertation will describe the chemical modification of medical grade polyurethane (PU), whose compliance has been shown to match that of native arteries. This modification will enable the immobilization of two proteins on an enzymatically relevant scale estimated at less than 10 nm. This dissertation will further describe the immobilization of the proteins TM and EPCR, and analyze the ability of a surface co-immobilized with these proteins to activate the anticoagulant PC. Finally, it will compare the ability of this co-immobilized surface to delay

  11. Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy--Creatine prophylaxis and the need for multi-organ protection.

    Science.gov (United States)

    Ellery, Stacey J; Dickinson, Hayley; McKenzie, Matthew; Walker, David W

    2016-05-01

    Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

    Science.gov (United States)

    Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

    2009-09-01

    One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

  13. Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

    Science.gov (United States)

    Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

    2016-04-01

    Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

  14. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history

    DEFF Research Database (Denmark)

    Park-Hansen, Jesper; Holme, Susanne J V; Irmukhamedov, Akhmadjon

    2018-01-01

    BACKGROUND: Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by l...

  15. Regulation of thrombomodulin expression and release in human aortic endothelial cells by cyclic strain.

    Directory of Open Access Journals (Sweden)

    Fiona A Martin

    Full Text Available Thrombomodulin (TM, an integral membrane glycoprotein expressed on the lumenal surface of vascular endothelial cells, promotes anti-coagulant and anti-inflammatory properties. Release of functional TM from the endothelium surface into plasma has also been reported. Much is still unknown however about how endothelial TM is regulated by physiologic hemodynamic forces (and particularly cyclic strain intrinsic to endothelial-mediated vascular homeostasis.This study employed human aortic endothelial cells (HAECs to investigate the effects of equibiaxial cyclic strain (7.5%, 60 cycles/min, 24 hrs, and to a lesser extent, laminar shear stress (10 dynes/cm2, 24 hrs, on TM expression and release. Time-, dose- and frequency-dependency studies were performed.Our initial studies demonstrated that cyclic strain strongly downregulated TM expression in a p38- and receptor tyrosine kinase-dependent manner. This was in contrast to the upregulatory effect of shear stress. Moreover, both forces significantly upregulated TM release over a 48 hr period. With continuing focus on the cyclic strain-induced TM release, we noted both dose (0-7.5% and frequency (0.5-2.0 Hz dependency, with no attenuation of strain-induced TM release observed following inhibition of MAP kinases (p38, ERK-1/2, receptor tyrosine kinase, or eNOS. The concerted impact of cyclic strain and inflammatory mediators on TM release from HAECs was also investigated. In this respect, both TNFα (100 ng/ml and ox-LDL (10-50 µg/ml appeared to potentiate strain-induced TM release. Finally, inhibition of neither MMPs (GM6001 nor rhomboids (3,4-dichloroisocoumarin had any effect on strain-induced TM release. However, significantly elevated levels (2.1 fold of TM were observed in isolated microparticle fractions following 7.5% strain for 24 hrs.A preliminary in vitro investigation into the effects of cyclic strain on TM in HAECs is presented. Physiologic cyclic strain was observed to downregulate TM

  16. A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

    NARCIS (Netherlands)

    Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

    2013-01-01

    Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

  17. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  18. Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

    Science.gov (United States)

    Yonezawa, S; Maruyama, I; Sakae, K; Igata, A; Majerus, P W; Sato, E

    1987-10-01

    Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

  19. The Role Of Protective Heat Shock Protein 70 And Proinflammatory Heat Shock Protein 60 Toward The Functional Status Of Acute Thrombotic Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Bertha Jean Que

    2015-08-01

    Full Text Available Abstract Clinical experience suggests that the functional status of stroke patients is not directly proportional to the number of risk factors this means that there are other factors that influence the status of functional role. The aim of this study is to explain the changes in levels of HSP70 and HSP60 associated with changes the functional status of stroke which measured with National Institutes of Health Stroke Scale NIHSS in acute thrombotic ischemic stroke. This research is quantitative research is an observational analytic with a longitudinal observational design prospective cohort study and case control. Data was collected by consecutive sampling. Examination of serum levels of HSP 70 HSP60 and assessment of NIHSS done in three times at the same time they are the first day amp8804 48 hours the third day 72 hours and fifth day 120 hours. There is a significant difference P 0.05 levels of HSP 60 and HSP 70 between patients with acute ischemic stroke cases with normal people control. Change dynamic level of HSP70 HSP60 and NIHSS according time of examination there is a significant difference. The first day of HSP 70 levels the third and fifth shaped the decline curve according to the NIHSS improvement while the levels of HSP60 formed a pattern opposite to the NIHSS. Curve levels of HSP70 and HSP60 levels to get to the point value of HSP 60 and HSP70 normal control. In general there was no effect of risk factors on extensive infarction NIHSS HSP70 and HSP60 except the variable age to HSP70 which in the elderly 70-75 years levels of HSP70 is higher than other age groups. Changes in levels of HSP70 and HSP60 follow the pattern of change in NIHSS towards improvement. Therefore HSP70 and HSP60 can serve as a prediction for degree of functional the acute thrombotic ischemic stroke. Risk factors are the cause of stroke but do not affect the NIHSS. Age affects levels of HSP 70. In general HSP60 and HSP70 can be used as a diagnostic and prognostic

  20. A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

    DEFF Research Database (Denmark)

    Bach, Anders*; Clausen, Bettina H; Møller, Magda

    2012-01-01

    Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are ...... of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke....

  1. Protective effects of alkaloid extract from Leonurus heterophyllus on cerebral ischemia reperfusion injury by middle cerebral ischemic injury (MCAO) in rats.

    Science.gov (United States)

    Liang, Hao; Liu, Ping; Wang, Yunshan; Song, Shuliang; Ji, Aiguo

    2011-07-15

    The neuronal damage following cerebral ischemia is a serious risk to stroke patients. The aim of this study was to investigate the neuroprotective effects of alkaloid extract from Leonurus heterophyllus (LHAE) on cerebral ischemic injury. After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), some rats were intraperitoneally administered different doses of LHAE (3.6, 7.2, 14.4 mg/kg, respectively). Neurological examination was measured in all animals. Infarct volume, myeloperoxidase (MPO) activity, levels of nitrate/nitrite metabolite (NO) and apoptosis ratio of nerve fiber in brain were determined. The results showed that LHAE at 7.2 mg/kg or 14.4 mg/kg exerted significantly decreasing neurological deficit scores and reducing the infarct volume on rats with focal cerebral ischemic injury (pagent. Further studies are warranted to assess the efficacy and safety of LHAE in patients. Copyright © 2011 Elsevier GmbH. All rights reserved.

  2. Early Menarche and Ischemic Stroke Risk Among Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Yi-Chen Hsieh

    2010-03-01

    Conclusion: Our study provides strong evidence that a significant joint protective effect was observed for patients who undergo early menarche, have longer estrogen exposure and no history of hypertension or diabetes mellitus on the risk of ischemic stroke.

  3. Ginsenoside Rg1 improves ischemic brain injury by balancing ...

    African Journals Online (AJOL)

    Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial ... and autophagy-related proteins were determined by reat time-polymerase chain ... Treatment with autophagy inhibitors decreased the mitochondrial protective ...

  4. The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

    Directory of Open Access Journals (Sweden)

    Rupak Pathak

    2016-11-01

    Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

  5. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  6. Enhancement of the blood compatibility of dialyzer membranes by the physical adsorption of human thrombomodulin (ART-123).

    Science.gov (United States)

    Omichi, Masaaki; Matsusaki, Michiya; Kato, Shinya; Maruyama, Ikuro; Akashi, Mitsuru

    2010-11-01

    ART-123 is a recombinant soluble human thrombomodulin (hTM) with excellent anticoagulant activity. We focused on improving the blood compatibility of the polysulfone-polyvinylpyrrolidone dialyzer surface by the physical adsorption of ART-123 onto the surface. The blood compatibility of the dialyzer with the hTM adsorbed membrane was evaluated by measuring the differential pressure between the arterial and the venous pressures and by blood parameters during blood circulation. The hTM adsorbed dialyzer membrane inhibited blood clot formation without heparin administration due to the anticoagulant activity of hTM for over 4 h. The physically adsorbed hTM was stable during blood circulation, and it did not affect activated clotting time, which is significant drawback of heparin administration, and blood cell counts of RBC, WBC, or platelets. The physical adsorption of hTM onto the dialyzer membrane will be a simple and safe method to prevent blood coagulation during dialysis instead of heparin administration. © 2010 Wiley Periodicals, Inc.

  7. Remote Ischemic Postconditioning (RIPC) of the Upper Arm Results in Protection from Cardiac Ischemia-Reperfusion Injury Following Primary Percutaneous Coronary Intervention (PCI) for Acute ST-Segment Elevation Myocardial Infarction (STEMI).

    Science.gov (United States)

    Cao, Bangming; Wang, Haipeng; Zhang, Chi; Xia, Ming; Yang, Xiangjun

    2018-02-19

    BACKGROUND The aim of this study was to evaluate the role of remote ischemic postconditioning (RIPC) of the upper arm on protection from cardiac ischemia-reperfusion injury following primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS Eighty patients with STEMI were randomized into two groups: primary PCI (N=44) and primary PCI+RIPC (N=36). RIPC consisted of four cycles of 5 minutes of occlusion and five minutes of reperfusion by cuff inflation and deflation of the upper arm, commencing within one minute of the first PCI balloon dilatation. Peripheral venous blood samples were collected before PCI and at 0.5, 8, 24, 48, and 72 hours after PCI. Levels of creatine kinase-MB (CK-MB), serum creatinine (Cr), nitric oxide (NO), and stromal cell-derived factor-1α (SDF-1α) were measured. The rates of acute kidney injury (AKI) and the estimated glomerular filtration rate (eGFR) were calculated. RESULTS Patients in the primary PCI+RIPC group, compared with the primary PCI group, had significantly lower peak CK-MB concentrations (PPCI in patients with acute STEMI might provide cardiac and renal protection from ischemia-reperfusion injury via the actions of SDF-1α, and NO.

  8. Toll-like Receptor 4 Signaling Confers Cardiac Protection Against Ischemic Injury via Inducible Nitric Oxide Synthase- and Soluble Guanylate Cyclase-dependent Mechanisms

    Science.gov (United States)

    Wang, E; Feng, Yan; Zhang, Ming; Zou, Lin; Li, Yan; Buys, Emmanuel S.; Huang, Peigen; Brouckaert, Peter; Chao, Wei

    2011-01-01

    Background Prior administration of a small dose of lipopolysaccharide confers a cardiac protection against ischemia-reperfusion injury. However, the signaling mechanisms that control the protection are incompletely understood. We tested the hypothesis that TLR4 mediates the ability of lipopolysaccharide to protect against cardiac ischemia-reperfusion injury through distinct intracellular pathways involving myeloid differentiation factor 88 (MyD88), TIR-domain-containing adaptor protein inducing interferon-β–mediated transcription-factor (Trif), inducible nitric-oxide synthase (iNOS), and soluble guanylate cyclase (sGC). Methods Wild-type mice and the genetically modified mice, i.e., TLR4-deficient (TLR4-def), TLR2 knockout (TLR2−/−), MyD88−/−, Trif−/−, iNOS−/−, and sGCα1−/−, were treated with normal saline or 0.1 mg/kg of lipopolysaccharide, intraperitoneally. Twenty-four hours later, isolated hearts were perfused in a Langendorff apparatus and subsequently subjected to 30 min of global ischemia and reperfusion for up to 60 min. Left ventricular function and myocardial infarction sizes were examined. Results Compared to saline-treated mice, lipopolysaccharide-treated mice had markedly improved left ventricular developed pressure and dP/dtmax (P < 0.01) and reduced MI sizes (37.2 ± 3.4% vs. 19.8 ± 4.9%, P < 0.01) after ischemia-reperfusion. The cardiac protective effect of lipopolysaccharide was abolished in the TLR4-def and MyD88−/− mice, but remained intact in TLR2−/− or Trif−/− mice. iNOS−/− mice or wild-type mice treated with the iNOS inhibitor 1400W failed to respond to the TLR4-induced nitric oxide production and were not protected by the lipopolysaccharide preconditioning. While sGC 1−/− mice had robust nitric oxide production in response to lipopolysaccharide, they were not protected by the TLR4-elicited cardiac protection. Conclusions TLR4 activation confers a potent cardiac protection against ischemia

  9. Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions.

    Directory of Open Access Journals (Sweden)

    Joy Ogbechi

    2015-07-01

    Full Text Available A well-known histopathological feature of diseased skin in Buruli ulcer (BU is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM expression on the surface of human dermal microvascular endothelial cells (HDMVEC at doses as low as 2 ng/ml and as early as 8 hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this

  10. Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

    DEFF Research Database (Denmark)

    Hauerslev, Marie; Mørk, Sivagowry Rasalingam; Pryds, Kasper

    2018-01-01

    Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Due to overlapping mechanisms this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term ...

  11. Ischemic necrosis and osteochondritis

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    Osteonecrosis indicates that ischemic death of the cellular constituents of bone and marrow has occurred. Historically, this first was thought to be related to sepsis in the osseous segments. However, continued studies led to the use of the term aseptic necrosis. Subsequent observations indicated that the necrotic areas of bone were not only aseptic, but were also avascular. This led to the terms ischemic necrosis, vascular necrosis and bone infarction. Ischemic necrosis of bone is discussed in this chapter. It results from a significant reduction in or obliteration of blood supply to the affected area. The various bone cells, including osteocytes, osteoclasts, and osteoblasts, usually undergo anoxic death in 12 to 48 hours after blood supply is cut off. The infarct that has thus developed in three-dimensional and can be divided into a number of zones: a central zone of cell death; an area of ischemic injury, most severe near the zone of cell death, and lessening as it moves peripherally; an area of active hyperemia and the zone of normal unaffected tissue. Once ischemic necrosis has begun, the cellular damage provokes an initial inflammatory response, which typically is characterized by vasodilatation, transudation of fluid and fibrin, and local infiltration of flammatory cells. This response can be considered the first stage in repair of the necrotic area

  12. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Atefeh Mahmoudi

    2013-11-01

    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

  13. Drug Delivery to the Ischemic Brain

    Science.gov (United States)

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  14. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1

    Directory of Open Access Journals (Sweden)

    Jingchun Guo

    2012-07-01

    Full Text Available Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1 protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

  15. Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

    Science.gov (United States)

    Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

    2018-05-01

    Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Ischemic strokes and migraine

    Energy Technology Data Exchange (ETDEWEB)

    Bousser, M.G.; Baron, J.C.; Chiras, J.

    1985-11-01

    Lasting neurological deficits, though most infrequent, do occur in migrainous subjects and are well documented by clinical angiographic computed tomographic (CT scan) and even pathological studies. However the mechanism of cerebral ischemia in migraine remains widely unknown and the precise role of migraine in the pathogenesis of ischemic strokes is still debated. (orig./MG).

  17. [Genetics of ischemic stroke].

    Science.gov (United States)

    Gschwendtner, A; Dichgans, M

    2013-02-01

    Stroke is one of the most widespread causes of mortality und disability worldwide. Around 80 % of strokes are ischemic and different forms of intracranial bleeding account for the remaining cases. Monogenic stroke disorders are rare but the diagnosis may lead to specific therapeutic consequences for the affected patients who are predominantly young. In common sporadic stroke, genetic factors play a role in the form of susceptibility genes. Their discovery may give rise to new therapeutic options in the future.

  18. Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

    Directory of Open Access Journals (Sweden)

    Trai-Ming Yeh

    Full Text Available Dengue virus (DV infections cause mild dengue fever (DF or severe life-threatening dengue hemorrhagic fever (DHF. The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM and macrophage migration inhibitory factor (MIF are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM and intercellular adhesion molecule-1 (ICAM-1 in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

  19. Association of postmenopausal hormone replacement therapy with carotid atherosclerosis and soluble thrombomodulin: the vascular aging (EVA) study. Etude du Vieillissement Artériel.

    Science.gov (United States)

    Petit, Laure; van Oort, Floor V A; Le Gal, Grégoire; Mennen, Louise I; Alhenc-Gelas, Martine; Touboul, Pierre-Jean; Zureik, Mahmoud; Scarabin, Pierre-Yves

    2002-02-15

    Hormone replacement therapy (HRT) may reduce atherosclerosis among postmenopausal women, partly by reducing vascular endothelium damage. We have tested this hypothesis by evaluating the association of HRT with firstly, carotid intima media thickness (IMT) and plaques, and secondly, with endothelial cell damage, indicated by soluble thrombomodulin (sTM). Then, we tested the association between the two markers of atherosclerosis and the levels of sTM. Among 747 postmenopausal women included into the EVA study, we compared 154 HRT users (including 80% transdermal treatment) with 593 never users. Carotid IMT and plaques were measured with B-mode ultrasonography and sTM with ELISA. At least one plaque was detected among 13.6% of HRT users and 27.3% of never users. After adjustment for confounding factors, the odds ratio for the presence of plaque was 0.45 (95% confidence interval, 0.25-0.78, P=0.005) in HRT users in comparison with nonusers. HRT users had a slightly lower crude mean IMT than nonusers, but the difference was not significant. sTM was positively associated with mean IMT (P for trend=0.001) but not with plaques. Finally, estrogen users had a lower sTM level than nonusers (difference 0.14 ng/ml, P=0.03). As HRT was associated with sTM and plaques, but not with IMT, while sTM was only associated with IMT, our hypothesis was not confirmed. This suggests that the possible beneficial effects of HRT on atherosclerosis may not go through the endothelial cell damage assessed by plasma thrombomodulin.

  20. Protection and repair of the ischemic heart

    NARCIS (Netherlands)

    Koudstaal, S.

    2014-01-01

    This thesis aimed to elucidate and advance strategies for cardioprotection and cardiac repair, translate preclinical findings towards future clinical studies and optimize the translational research process for IHD. So far, many cardioprotective strategies against reperfusion injury could not be

  1. Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery

    DEFF Research Database (Denmark)

    Holmberg, Fredrik Eric Olof; Ottas, Konstantin Alex; Andreasen, Charlotte

    2014-01-01

    OBJECTIVES: The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic...

  2. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    OpenAIRE

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects...

  3. The ischemic perinatal brain damage

    International Nuclear Information System (INIS)

    Crisi, G.; Mauri, C.; Canossi, G.; Della Giustina, E.

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis

  4. Neurovascular regulation in the ischemic brain.

    Science.gov (United States)

    Jackman, Katherine; Iadecola, Costantino

    2015-01-10

    The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

  5. Effects of ketamine and its isomers on ischemic preconditioning in the isolated rat heart

    NARCIS (Netherlands)

    Molojavyi, A.; Preckel, B.; Comfère, T.; Müllenheim, J.; Thämer, V.; Schlack, W.

    2001-01-01

    BACKGROUND: Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of

  6. Genetic inhibition of CETP, ischemic vascular disease and mortality, and possible adverse effects

    DEFF Research Database (Denmark)

    Johannsen, Trine Holm; Frikke-Schmidt, Ruth; Schou, Jesper

    2012-01-01

    This study tested whether genetic variation in the CETP gene is consistent with a protective effect of cholesteryl ester transfer protein (CETP) inhibition on risk of ischemic events and on total mortality, without the adverse effects reported for torcetrapib.......This study tested whether genetic variation in the CETP gene is consistent with a protective effect of cholesteryl ester transfer protein (CETP) inhibition on risk of ischemic events and on total mortality, without the adverse effects reported for torcetrapib....

  7. Hemichorea after ischemic stroke

    Directory of Open Access Journals (Sweden)

    Sadullah Saglam

    2016-03-01

    Full Text Available The deterioration of the balance between direct and indirect ways in the basal ganglia causes chorea. The lesions of contralateral basal ganglia, thalamus or the connection of them all together are responsible for this. Chorea can be observed during the course of metabolic and vascular diseases, neurodegenerative or hereditary diseases. Hyperkinetic movement disorders after acute ischemic stroke are reported as rare; however, hemichorea is the most frequent developing disorder of hyperkinetic movement as a result of cerebrovascular disease. In this case report, we presented two case who applied us with choreiform movements in his left half of the body after acute thalamic stroke. [Cukurova Med J 2016; 41(0.100: 29-32

  8. Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Rezvani

    2012-01-01

    Full Text Available Background: The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. Materials and Methods: A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD and Ischemic Stroke (IS was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Results: Five hundred fifty eight patients (307 females, 251 males with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000 respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020. Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Conclusion: Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occur r ence of IS and IHD.

  9. Is opium addiction a risk factor for ischemic heart disease and ischemic stroke?

    Science.gov (United States)

    Rezvani, Mohammad Reza; Ghandehari, Kavian

    2012-10-01

    The main source of studies about effects of opium consumption on heart and brain attacks originates from Iran Therefore the aim of the present study was to assess opium addiction as a probable influencing factor for ischemic heart disease and ischemic stroke. A cross-sectional study was carried out in two Cardiology and Neurology clinics in Eastern Iran in 2011. Diagnosis of Ischemic Heart Disease (IHD) and Ischemic Stroke (IS) was made by Cardiologist and Stroke Neurologist respectively. The influence of gender, hypertension, diabetes, hyperlipidemia, cigarette smoking, oral and inhaled opium consumption on distribution of IHD and IS were evaluated. Five hundred fifty eight patients (307 females, 251 males) with mean age 56.2 years enrolled the study. On adjusted odds ratios of our whole 558 patients, only hypertension and diabetes had a significant influence on occurrence of IHD; (P = 0.000 and P = 0.000) respectively. Oral and inhaled routes of opium addiction did not have a significant effect on occurrence of IHD; [OR = 1.172, 95% CI = 0.624-2.203, P = 0.621] and [OR = 1.820, 95% CI = 0.811-4.085, P = 0.147] respectively. Hypertension and diabetes were significant risk factors of IS in our 558 patients at multivariate analysis; (P = 0.000, P = 0.020). Oral opium addiction was as significant protective factor of IS in our study group; OR = 0.211, 95% CI = 0.079-0.564, P = 0.002, while inhaled opium addiction did not have a significant effect on occurrence of IS in our patients at; OR = 1.760, 95% CI = 0.760-4.076, P = 0.187. Oral opium consumption is a protective factor of IS but not IHD. Inhaled opium addiction does not have a significant influence on occurrence of IS and IHD.

  10. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  11. Estudo comparativo entre o pré-condicionamento isquêmico e a drenagem liquórica como métodos de proteção medular em cães Comparative study between ischemic preconditioning and cerebrospinal fluid drainage as methods of spinal cord protection in dogs

    Directory of Open Access Journals (Sweden)

    Anderson Benício

    2007-03-01

    after the procedure, Tarlov scores were significantly higher only in the Drainage Group when compared to the Control Group (p<0.05. Lower SSEP recovery times were also observed with cerebrospinal fluid drainage during the final reperfusion period (p<0.01. In the histopathologic study, stain showed less significant neuronal necrosis in the thoracic and lumbar gray matter in animals submitted to both methods of spinal cord protection, with it being more pronounced in the Ischemic Preconditioning Group (p<0.001. CONCLUSION: Cerebrospinal fluid drainage and immediate ischemic preconditioning seems to protect the spinal cord during descending thoracic aorta cross-clamping. Nevertheless, the obtained level of spinal cord protection seems to be more significant with cerebrospinal fluid drainage.

  12. Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Ruth E.Rosenstein; Diego C.Fernandez

    2014-01-01

    Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti-nopathy have focused either on highly speciifc therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis-tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch-emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.

  13. [The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia].

    Science.gov (United States)

    Blokhin, I O; Galagudza, M M; Vlasov, T D; Nifontov, E M; Petrishchev, N N

    2008-07-01

    Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.

  14. MRI in ischemic heart disease

    International Nuclear Information System (INIS)

    Hazirolan, T.

    2012-01-01

    Full text: The role of magnetic resonance imaging in the evaluation of ischemic heart disease has increased over the last years. Cardiac MRI is the only imaging modality that provides 'one stop shop' assessment. Information about ventricular function, myocardial ischemia and myocardial viability can be obtained in a single cardiac MRI session. Additionally, Cardiac MRI has become a gold standard method in evaluation of myocardial viability and in assessment of ventricular mass and function. As a result, cardiac MRI enable radiologist to comprehensively assess ischemic heart disease. The aim of this presentation is to provide the reader a state-of-the art on how the newest cardiac MRI techniques can be used to study ischemic heart disease patients.

  15. MR imaging of ischemic penumbra

    International Nuclear Information System (INIS)

    Abe, Osamu; Aoki, Shigeki; Shirouzu, Ichiro; Kunimatsu, Akira; Hayashi, Naoto; Masumoto, Tomohiko; Mori, Harushi; Yamada, Haruyasu; Watanabe, Makoto; Masutani, Yoshitaka; Ohtomo, Kuni

    2003-01-01

    Cerebral ischemic stroke is one of the most fatal diseases despite current advances in medical science. Recent demonstration of efficacy using intravenous and intra-arterial thrombolysis demands therapeutic intervention tailored to the physiologic state of the individual tissue and stratification of patients according to the potential risks for therapies. In such an era, the role of the neuroimaging becomes increasingly important to evaluate the extent and location of tissues at risk of infarction (ischemic penumbra), to distinguish it from unsalvageable infarcted tissues or doomed hemorrhagic parenchyma. In this review, we present briefly the current role and limitation of computed tomography and conventional magnetic resonance imaging (MRI). We also present the possible applications of advanced MR techniques, such as diffusion and perfusion imaging, concentrating on the delineation or detection of ischemic penumbra

  16. Mechanisms of gender-linked ischemic brain injury

    Science.gov (United States)

    Liu, Mingyue; Dziennis, Suzan; Hurn, Patricia D.; Alkayed, Nabil J.

    2010-01-01

    Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke. We review recent advances in our understanding of sex steroids (estradiol, progesterone and testosterone) in the context of ischemic cell death and neuroprotection. Understanding the molecular and cell-based mechanisms underlying sex differences in ischemic brain injury will lead to a better understanding of basic mechanisms of brain cell death and is an important step toward designing more effective therapeutic interventions in stroke. PMID:19531872

  17. Unilateral anterior ischemic optic neuropathy

    DEFF Research Database (Denmark)

    Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik

    2013-01-01

    of this study was to investigate the ipRGC mediated pupil response in patients with a unilateral non-arteritic anterior ischemic optic neuropathy (NAION). Consensual pupil responses during and after exposure to continuous 20 s blue (470 nm) or red (660 nm) light of high intensity (300 cd/m(2)) were recorded...

  18. [Ischemic stroke in young women

    NARCIS (Netherlands)

    Ekker, M.S.; Wermer, M.J.; Riksen, N.P.; Klijn, C.J.; Leeuw, F.E. de

    2016-01-01

    - In virtually all age groups, the incidence of ischemic stroke is higher in men. However, in women aged between 25-49 years the prevalence is higher than in men. Female-specific risk factors and disorders may explain this peak.- Pregnancy and the post-partum period are associated with physiological

  19. Diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Bergmann, Natasha; Ballegaard, Søren; Holmager, Pernille

    2014-01-01

    The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two...

  20. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    Esteban Sáez-González

    Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

  1. Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

    Directory of Open Access Journals (Sweden)

    Nicholas Caffes

    2015-03-01

    Full Text Available Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4 channels and, in some cases, microglial KATP (Sur1–Kir6.2 channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

  2. Glibenclamide for the treatment of ischemic and hemorrhagic stroke.

    Science.gov (United States)

    Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

    2015-03-04

    Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

  3. Hypertension and Ischemic Heart Disease in Women.

    Science.gov (United States)

    Dorobantu, Maria; Onciul, Sebastian; Tautu, Oana Florentina; Cenko, Edina

    2016-01-01

    Ischemic heart disease (IHD) is the most important cause of mortality worldwide. Although the awareness of cardiovascular risk factors and IHD in women has increased over the last decades, mortality rates are still higher in women than in men. Among traditional cardiovascular risk factors, hypertension is associated with a greater risk for IHD in women as compared to men. In this review, discuss gender differences in epidemiology and pathophysiology of hypertension and its impact on the incidence and outcomes of IHD in women. We also, discuss some "women conditions" such as hypertensive disorders in pregnancy (HDP) and polycystic ovarian syndrome (PCOS). Even though this is not a systematic review, English-language studies on MEDLINE and the Cochrane Database of Systematic reviews were searched for consultation and analysis. Hypertension display different epidemiological patterns in men and women. Studies have shown that hypertension has a different proatherogenic effects in men and women. Hypertension has a direct effect on microcirculation, but estrogens have a protective role in this regard in premenopausal women. However, after the decline in estrogen levels, women are exposed to the same cardiovascular risk as males. Postmenopausal women exhibit a greater burden of cardiovascular risk factors, which together with microvascular dysfunction and smaller and stiffer arteries conducts to the worse prognosis observed in women with IHD. "Women specific conditions" such as HDP and PCOS affects 10% of pregnant women and women in reproductive age, respectively. These conditions are associated with increased risk of hypertension and IHD later in life. Although women are more aware of their hypertension, cardiovascular mortality is higher in hypertensive women with comorbid IHD. Yet these gender disparities in outcomes seem to be attenuated with effective therapy. The pathophysiology of IHD is gender specific, women with ischemic symptoms presenting less often with

  4. Melatonin and Ischemic Stroke: Mechanistic Roles and Action

    Directory of Open Access Journals (Sweden)

    Syed Suhail Andrabi

    2015-01-01

    Full Text Available Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

  5. Melatonin and Ischemic Stroke: Mechanistic Roles and Action.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2015-01-01

    Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca(2+) level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke.

  6. Role of homocysteine in the ischemic stroke nad development of ischemic tolerance

    Directory of Open Access Journals (Sweden)

    Jan Lehotsky

    2016-11-01

    Full Text Available Homocysteine (Hcy is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy, as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signalling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signalling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors

  7. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure

    Directory of Open Access Journals (Sweden)

    Kyoung-Im Cho

    2014-08-01

    Full Text Available Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF, and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI-induced heart failure (HF rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group and underwent echocardiography, AF induction studies and left atrial (LA fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX, sarcoplasmic reticulum calcium ATPase (SERCA, endothelial nitric oxide synthase (eNOS and induced nitric oxide synthase (iNOS were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham, which were significantly reduced by simvastatin (p < 0.05 vs. MI. The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.

  8. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    OpenAIRE

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program....

  9. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

    Science.gov (United States)

    Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

    2016-04-07

    Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; Pischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

  10. The application of remote ischemic conditioning in cardiac surgery [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Zeljko J. Bosnjak

    2017-06-01

    Full Text Available Perioperative myocardial ischemia and infarction are the leading causes of morbidity and mortality following anesthesia and surgery. The discovery of endogenous cardioprotective mechanisms has led to testing of new methods to protect the human heart. These approaches have included ischemic pre-conditioning, per-conditioning, post-conditioning, and remote conditioning of the myocardium. Pre-conditioning and per-conditioning include brief and repetitive periods of sub-lethal ischemia before and during prolonged ischemia, respectively; and post-conditioning is applied at the onset of reperfusion. Remote ischemic conditioning involves transient, repetitive, non-lethal ischemia and reperfusion in one organ or tissue (remote from the heart that renders myocardium more resistant to lethal ischemia/reperfusion injury. In healthy, young hearts, many conditioning maneuvers can significantly increase the resistance of the heart against ischemia/reperfusion injury. The large multicenter clinical trials with ischemic remote conditioning have not been proven successful in cardiac surgery thus far. The lack of clinical success is due to underlying risk factors that interfere with remote ischemic conditioning and the use of cardioprotective agents that have activated the endogenous cardioprotective mechanisms prior to remote ischemic conditioning. Future preclinical research using remote ischemic conditioning will need to be conducted using comorbid models.

  11. Peripheral Mechanisms of Ischemic Myalgia

    Directory of Open Access Journals (Sweden)

    Luis F. Queme

    2017-12-01

    Full Text Available Musculoskeletal pain due to ischemia is present in a variety of clinical conditions including peripheral vascular disease (PVD, sickle cell disease (SCD, complex regional pain syndrome (CRPS, and even fibromyalgia (FM. The clinical features associated with deep tissue ischemia are unique because although the subjective description of pain is common to other forms of myalgia, patients with ischemic muscle pain often respond poorly to conventional analgesic therapies. Moreover, these patients also display increased cardiovascular responses to muscle contraction, which often leads to exercise intolerance or exacerbation of underlying cardiovascular conditions. This suggests that the mechanisms of myalgia development and the role of altered cardiovascular function under conditions of ischemia may be distinct compared to other injuries/diseases of the muscles. It is widely accepted that group III and IV muscle afferents play an important role in the development of pain due to ischemia. These same muscle afferents also form the sensory component of the exercise pressor reflex (EPR, which is the increase in heart rate and blood pressure (BP experienced after muscle contraction. Studies suggest that afferent sensitization after ischemia depends on interactions between purinergic (P2X and P2Y receptors, transient receptor potential (TRP channels, and acid sensing ion channels (ASICs in individual populations of peripheral sensory neurons. Specific alterations in primary afferent function through these receptor mechanisms correlate with increased pain related behaviors and altered EPRs. Recent evidence suggests that factors within the muscles during ischemic conditions including upregulation of growth factors and cytokines, and microvascular changes may be linked to the overexpression of these different receptor molecules in the dorsal root ganglia (DRG that in turn modulate pain and sympathetic reflexes. In this review article, we will discuss the

  12. Sex Hormones and Ischemic Stroke

    DEFF Research Database (Denmark)

    Holmegard, Haya N; Nordestgaard, Børge G; Jensen, Gorm B

    2016-01-01

    CONTEXT AND OBJECTIVE: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. DESIGN, SETTING, AND PARTICIPANTS: Adult men (n...... = 4615) and women (n = 4724) with measurements of endogenous sex hormones during the 1981-1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through...

  13. Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study.

    Science.gov (United States)

    Jauch, Edward C; Lindsell, Christopher; Broderick, Joseph; Fagan, Susan C; Tilley, Barbara C; Levine, Steven R

    2006-10-01

    Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100beta, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome. In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at approximately 2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy. Higher 24-hour peak concentrations of MBP, NSE, and S100beta were associated with higher National Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117, P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure. This study corroborates previous work demonstrating correlations of MBP, NSE, and S100beta with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator-treated group, we

  14. 25-Hydroxyvitamin D and symptomatic ischemic stroke

    DEFF Research Database (Denmark)

    Brøndum-Jacobsen, Peter; Nordestgaard, Børge G; Schnohr, Peter

    2013-01-01

    City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events. RESULTS: Stepwise decreasing plasma 25-hydroxyvitamin D concentrations...

  15. Cerebral ischemic stroke: is gender important?

    Science.gov (United States)

    Gibson, Claire L

    2013-09-01

    Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke.

  16. Molecular Mechanisms of Renal Ischemic Conditioning Strategies

    DEFF Research Database (Denmark)

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J; Krogstrup, Nicoline V

    2015-01-01

    summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many...

  17. Genetic variation in WRN and ischemic stroke

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Nordestgaard, Børge G.

    2017-01-01

    trends for ischemic cerebrovascular disease (P = 0.06). In meta-analyses including 59,190 individuals in 5 studies, the hazard ratio for ischemic stroke for C1367R TT homozygotes versus CC/CT was 1.14 (1.04–1.25; P = 0.008). Conclusions This study suggests that common genetic variation in WRN......Background Werner syndrome, a premature genetic aging syndrome, shares many clinical features reminiscent of normal physiological aging, and ischemic vascular disease is a frequent cause of death. We tested the hypothesis that genetic variation in the WRN gene was associated with risk of ischemic...... vascular disease in the general population. Methods We included 58,284 participants from two general population cohorts, the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS). Of these, 6,312 developed ischemic vascular disease during follow-up. In the CCHS (n = 10...

  18. Swallowing disorders after ischemic stroke

    Directory of Open Access Journals (Sweden)

    Gabriela Camargo Remesso

    2011-10-01

    Full Text Available OBJECTIVE: To investigate occurrences of swallowing disorders after ischemic stroke. METHOD: This was a retrospective study on 596 medical files. The inclusion criterion was that the patients needed to have been hospitalized with a diagnosis of ischemic stroke; the exclusion criteria were the presence of associated cardiac problems and hospital stay already more than 14 days. RESULTS: 50.5% were men and 49.5% women; mean age 65.3 years (SD=±11.7 (p<0.001. Among the risk factors, 79.4% had hypertension, 36.7% had diabetes (p<0.001 and 42.7% were smokers. 13.3% of the patients died. Swallowing disorders occurred in 19.6%, among whom 91.5% had mild difficulty and 8.5% had severe difficulty. 87.1% had spontaneous recovery after a mean of 2.4 months. A lesion in the brainstem region occurred in 6.8% (p<0.001. CONCLUSION: Swallowing disorders occurred in almost 20% of the population and most of the difficulty in swallowing found was mild. The predictors for swallowing disorders were older age, diabetes mellitus and lesions in the brainstem region.

  19. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    International Nuclear Information System (INIS)

    Li, Zhao; Jin, Zhu-Qiu

    2012-01-01

    Highlights: ► Cardiac tight junctions are present between coronary endothelial cells. ► Ischemic preconditioning preserves the structural and functional integrity of tight junctions. ► Myocardial edema is prevented in hearts subjected to ischemic preconditioning. ► Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood–heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs–Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in

  20. Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Zhou-Quan Wu

    2016-01-01

    Full Text Available This study is aimed at investigating the association between the electroacupuncture (EA pretreatment-induced protective effect against early cerebral ischemic injury and autophagy. EA pretreatment can protect cerebral ischemic and reperfusion injuries, but whether the attenuation of early cerebral ischemic injury by EA pretreatment was associated with autophagy is not yet clear. This study used the middle cerebral artery occlusion model to monitor the process of ischemic injury. For rats in the EA pretreatment group, EA pretreatment was conducted at Baihui acupoint before ischemia for 30 min for 5 consecutive days. The results suggested that EA pretreatment significantly increased the expression of autophagy in the cerebral cortical area on the ischemic side of rats. But the EA pretreatment-induced protective effects on the brain could be reversed by the specific inhibitor 3-methyladenine of autophagy. Additionally, the Pearson correlation analysis indicated that the impact of EA pretreatment on p-mTOR (2481 was negatively correlated with its impact on autophagy. In conclusion, the mechanism of EA pretreatment at Baihui acupoint against cerebral ischemic injury is mainly associated with the upregulation of autophagy expression, and its regulation of autophagy may depend on mTOR-mediated signaling pathways.

  1. Functional reconstruction of ischemic contracture in the

    Directory of Open Access Journals (Sweden)

    TANG Hao

    2011-04-01

    Full Text Available 【Abstract】Objective: To discuss the method of functional reconstruction of ischemic contracture in the lower limb and propose a classification protocol for ischemic contracture in the lower limb based on its severity and prognosis. Methods: A total of 42 patients with ischemic contracture in the lower limb were included in this study. According to different types of disturbance and degrees of severity, surgical reconstructions consisting of nerve decompression, tendon lengthening or transfer, intrinsic foot muscle release and sural-tibial nerve anastomosis were performed in every patient. Results: Postoperatively, all patients were able to walk on flat ground. Drop foot was corrected in 10 patients, and 5 patients still felt some difficulty during stair activity. Split Achilles tendon transfer to flexor hallucis longus tendon was performed in 12 patients, and their walking stability was improved. Seven patients accepted ipsilateral suraltibial nerve anastomosis, and sensitivity recovery reached to S2 in 2 patients and S3 in 5 patients. Conclusions: Ischemic contracture in the lower limb is a devastating complication after lower limb trauma. The prevention of contracture is much more important than the treatment of an established contracture. Split Achilles tendon transfer to flexor hallucis longus tendon and sural-tibial nerve anastomosis, which was initially implemented by us, could improve the functional recovery of ischemic contracture in lower limbs, and thus provides a new alternative for functional reconstruction of ischemic contracture in the lower limb. Key words: Ischemic contracture; Classification; Recovery of function

  2. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Ralph R E G Geuskens

    Full Text Available CT perfusion (CTP is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0. Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT regions. False discovery ratio (FDR, defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml; median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml. Median FDR between patients was 62% (IQR:49%-80%. Median relative mean transit time was 243% (IQR:198%-289% and 342% (IQR:249%-432% for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79 ml/100g (P<0.01 and 1.38 (IQR:1.15-1.49 ml/100g (P<0.01 for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly

  3. Transient ischemic attack: diagnostic evaluation.

    Science.gov (United States)

    Messé, Steven R; Jauch, Edward C

    2008-08-01

    A transient ischemic attack portends significant risk of a stroke. Consequently, the diagnostic evaluation in the emergency department is focused on identifying high-risk causes so that preventive strategies can be implemented. The evaluation consists of a facilitated evaluation of the patient's metabolic, cardiac, and neurovascular systems. At a minimum, the following tests are recommended: fingerstick glucose level, electrolyte levels, CBC count, urinalysis, and coagulation studies; noncontrast computed tomography (CT) of the head; electrocardiography; and continuous telemetry monitoring. Vascular imaging studies, such as carotid ultrasonography, CT angiography, or magnetic resonance angiography, should be performed on an urgent basis and prioritized according to the patient's risk stratification for disease. Consideration should be given for echocardiography if no large vessel abnormality is identified.

  4. Genetics of ischemic stroke: future clinical applications.

    Science.gov (United States)

    Wang, Michael M

    2006-11-01

    Ischemic stroke has long been thought to have a genetic component that is independent of conventional vascular risk factors. It has been estimated that over one half of stroke risk is determined by inherited genes. However, until recently, strong evidence of genetic influence on ischemic stroke has been subject to criticism because the risk factors for stroke are also inherited and because previous studies suffered from limitations imposed by this highly heterogeneous neurological disorder. Recent advances in molecular genetics have led to the identification of specific genetic loci that impart susceptibility to ischemic stroke. We review the studies of these genes and discuss the future potential applications of genetic markers on the management of ischemic stroke patients.

  5. Prognostic Factors in Ischemic Arterial Stroke

    OpenAIRE

    J Gordon Millichap

    2001-01-01

    The predictive value of presenting symptoms, MRI and CT findings, and etiology in the outcome of ischemic arterial childhood stroke was determined in a consecutive series of 31 patients followed at the University Hospital, Rotterdam, The Netherlands.

  6. [Primary emergencies: management of acute ischemic stroke].

    Science.gov (United States)

    Leys, Didier; Goldstein, Patrick

    2012-01-01

    The emergency diagnostic strategy for acute ischemic stroke consists of:--identification of stroke, based on clinical examination (sudden onset of a focal neurological deficit);--identification of the ischemic or hemorrhagic nature by MRI or CT;--determination of the early time-course (clinical examination) and the cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same general management (treatment of a life-threatening emergency, ensuring normal biological parameters except for blood pressure, and prevention of complications);--decompressive surgery in the rare cases of intracranial hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for patients admitted with 4.5 hours of stroke onset who have no contraindications, and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These treatments should be administered within a few hours. A centralized emergency call system (phone number 15 in France) is the most effective way of achieving this objective.

  7. Acute ischemic stroke prognostication, comparison between ...

    African Journals Online (AJOL)

    Ossama Y. Mansour

    2014-11-20

    Nov 20, 2014 ... patients with acute ischemic stroke in comparison with the NIHSS and the GCS. Methods: .... All patients received a CT scan of the brain on admission. Diagnostic ... adjusted for age, sex, Charlson Index and Oxfordshire. 248.

  8. Ischemic Stroke: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Thrombolytic therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Ischemic Stroke updates ... cardiogenic embolism Stroke - slideshow Thrombolytic therapy Related Health Topics Hemorrhagic Stroke Stroke Stroke Rehabilitation National Institutes of ...

  9. Paraneoplastic Ischemic Stroke: Case Report and Review

    Directory of Open Access Journals (Sweden)

    Murat Sumer

    2008-10-01

    Full Text Available OBJECTIVE: Paraneoplastic etiology is not frequent among cerebrovascular disorders. This rare disorder is interesting with different mechanisms, clinical manifestations and treatment options. Diagnosis may be overlooked for its rarity. We present a paraneoplastic ischemic stroke patient with its clinical and imaging characteristics for recalling this rare disease. CASE: A sixty years old woman with a history of ovarian and colon cancer and liver metastasis admitted with acute left sided hemiplegia. Brain magnetic resonance imaging showed multiple ischemic lesions at the same age. Laboratory findings were compatible with chronic disseminated intravascular coagulopathy. She was anticoagulated but the clinical findings were not changed. She died one month after her discharge from the hospital. CONCLUSIONS: Paraneoplastic ischemic stroke is rare and it should be recognized by the clinician to differentiate from other ischemic strokes by its different mechanisms, imaging characteristics and treatment modalities. Prognosis depends on the characteristics of the primary tumor

  10. Role of neuroinflammation in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

    2017-01-01

    Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

  11. Transient central diabetes insipidus following ischemic stroke

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Jayaraman

    2013-01-01

    Full Text Available Central Diabetes Insipidus (CDI following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery.

  12. Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model

    International Nuclear Information System (INIS)

    Choi, Samjin; Lee, Gi-Ja; Chae, Su-Jin; Kang, Sung Wook; Park, Hun-Kuk; Yin, Chang-Shik; Lee, Seung-Hoon; Choi, Seok Keun

    2010-01-01

    Acupuncture (ACU) is known to be effective in ischemia treatment, and glutamate (GLU) excitotoxicity is an important factor in neuronal cell death. We observed the effect of ACU on cerebral blood flow (%CBF) and ΔGLU (the changes in GLU release) in the ischemic stroke rat model of diabetic mellitus (DM). A global ischemia was induced using the eleven-vessel occlusion (11-VO) method in 14 Sprague-Dawley rats (DM), which were randomly divided into two groups: the control group and the ACU-treatment group. Extracellular ΔGLU was assessed using an intra-cerebral biosensor system measuring 256 samples per second, simultaneously with %CBF and electroencephalogram. ACU stimulation was applied to ACU points GB34 and GB39 during the ischemic period. Twenty-three diagnostic parameters were proposed first for a detailed analysis of changes in %CBF and GLU release during ischemia/reperfusion. ACU rats showed a significant decrease in ischemic (p < 0.05) and reperfusion %CBF (p < 0.0001) than control rats, and a significantly larger decrease in ischemic ΔGLU (p < 0.05) and peak level of reperfusion ΔGLU (p < 0.005) than control rats. From these results, we suggest that ACU stimulation is responsible for the potential protection of neurons through suppression of %CBF response in the increased plasma osmolality and extracellular ΔGLU in diabetic rats under ischemic conditions

  13. Association of nNOS Gene Polymorphism with Ischemic Stroke in Han Chinese of North China

    Directory of Open Access Journals (Sweden)

    Yingjie Dai

    2013-01-01

    Full Text Available Nitric oxide (NO is an important messenger molecule and effector molecule. This study aimed to investigate the relation of neuronal nitric oxide synthase (nNOS gene polymorphism with ischemic stroke in Han Chinese of North China. This was a case-control study. A total of 413 patients with ischemic stroke were recruited from Han Chinese of North China. There were 201 males and 212 females. In addition, 477 healthy subjects served as controls including 224 males and 253 females. Multiplex SNaPshot was employed to detect nNOS gene polymorphism (rs2293050, rs2139733, rs7308402, and rs1483757. Results showed that the rs1483757, rs2139733, and rs2293050 genotypes and allele frequencies were comparable between patients and controls. However, ischemic stroke patients had significantly reduced AG genotype and A allele frequency when compared with controls (P=0.037, P=0.041. After adjusting confounding factors (gender, age, smoking, history of drinking, hypertension, and diabetes, AG genotype and A allele were still related to ischemic stroke (OR=0.572, 95% CI: 0.335–0.978, P=0.041; OR=0.611, 95% C: 0.378–0.985, and P=0.041 and both were found to be protective factors. Our results showed that rs7308402 gene polymorphism of nNOS is related to ischemic stroke in Han Chinese of North China.

  14. [Molecular mechanisms of ischemic-reperfusion syndrome and its personalized therapy].

    Science.gov (United States)

    Grebenchikov, O A; Likhvantsev, V V; Plotnikov, E Iu; Silachev, D N; Pevzner, I B; Zorova, L D; Zorov, D B

    2014-01-01

    Cardiovascular pathologies are the major causes of morbidity and mortality in the world. Cessation of the blood flow in large vessels, supplying tissues with oxygen and substrates, leads to ischemic conditions accompanied by unwanted shifts of oxidative metabolism and rise of the reactive oxygen species (ROS) generation. Small amounts of ROS are essential elements of the cell metabolism, however pathological elevation of ROS jeopardizes the survival of cells, organs and even organisms. Paradoxically, blood flow restoration during prolonged ischemia leads to oxidative stress that is often fatal for a live system. Oxygen paradox appears to be a limiting factor in clinical practice that intuitively seeks for immediate and complete restoration of a damaged blood flow. Mitochondrion is a major ROS source and a key element of pro-apoptotic signaling, however it is clear, that mitochondria are the main target for anti-ischemic treatment. In the present review we consider two ways of such anti-ischemic strategy, bringing ischemic tolerance to the organ through mitochondrial involvement, such as intrinsic, biological, or artificial, pharmacological adaptive systems (preconditioning). The latter is aimed to simulate elements and high efficiency of intrinsic protective system. The role of antioxidants in anti-ischemic therapy and their effects on preconditioning signaling are discussed in the review.

  15. Effects Of Ischemic Preconditioning On The Renal Ischemia- Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Anyamanesh S

    2003-07-01

    Full Text Available  During kidney and other organ transplantation, the organ to be transplanted, must inevitably remain out of the body with little or no blood perfusion at all for a long period of time (ischemia. These events have been suggested to cause the formation of oxygen- derived free radicals (OFR. Reperfusion (reintroduction of blood flow will further exacerbate the initial damage caused by the ischemic insult and may result in the production of free radicals. The aim of this study was to investigate whether induction of brief periods of renal artery occlusion (ischemic pre¬conditioning, IPC can provide protection from the effects of a subsequent period of ischemia and reperfusion (IR in the rat kidney."nMaterials and Methods: In this regard, 28 white, male rats were randomly and equally divided into four groups: Control (sham- operated, IPC alone, IR alone (30 min ischemia followed by 10 min reperfusion, and IPC- IR. Preconditioning involved the sequential clamping of the right renal artery for 5 min and declamping for 5 min for a total of 3 cycles. To demonstrate the effectiveness of IPC regimen, vitamin E as an endogenous antioxidant and an index of lipid peroxidation was measured by HPLC after its extraction from right renal venous plasma and right renal tissue."nResults: Results of this study showed that the amount of vitamin E of renal tissue and venous plasma in the IR group had a significant decrease when compared to the control group (P< 0.0001. Whereas the amount of this vitamin in both renal tissue and venous plasma of the IPC- IR group was significantly higher than that in the IR group (P< 0.0001, but did not show any significant difference with the control group."nConclusion: In this study, preconditioning method prevented the reduction of the endogenous antioxidant (Vit. E in encountering the following sustained ischemic insult. Therefore, we suggest that ischemic preconditioning can be used to protect the Vit. E level of kidney from its

  16. [Brain protection against cerebral ischemia].

    Science.gov (United States)

    Kitagawa, Kazuo

    2013-01-01

    Previous clinical trials failed to show the benefit of several potentially protective drugs in acute ischemic stroke. However, there would be three main approaches for brain protection against stroke. The first is to develop a novel thrombolytic agent which is more efficient and safer than alteplase. Tenecteplase and desmoteplase are in progress as a new thrombolytic drug. The second strategy is to augment collateral circulation through leptomeningeal anastomosis. Administration of G-CSF could enhance arteriogenesis, but it takes several days to develop functional collateral. For this purpose, partial aortic balloon clumping or stimulation of pterygopalatine ganglion may be promising. The third one is to protect neurovascular unit against reperfusion injury. Brain hypothermia is the most effective strategy in experimental ischemia, and the clinical trial for hypothermia combined with thrombolysis therapy is in progress. Activation of endogenous protective response, as presented by ischemic tolerance, has focused on remote ischemic conditioning. Although the precise mechanisms of remote preconditioning remain unclear, intermittent limb ischemia is a safe approach. Remote ischemic conditioning is now investigated in acute patients with thrombolysis therapy.

  17. Genetically elevated C-reactive protein and ischemic vascular disease

    DEFF Research Database (Denmark)

    Zacho, J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2008-01-01

    Background: Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association. Methods: We studied 10,276 persons from a general population cohort, including 1786 in whom...... ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients...... with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms. Results: The risk of ischemic heart...

  18. MRI in ischemic brain diseases

    International Nuclear Information System (INIS)

    Steinbrich, W.; Friedmann, G.; Pawlik, G.; Boecher-Schwarz, H.G.; Heiss, W.D.

    1986-01-01

    The results of MRI and CT in 55 patients with brain infarcts were compared; in 26 of these cases an additional PET examination was obtained in order to study the regional glucose utilisation. MRI was superior to CT, demonstrating 11% more of the infarcts, particularly during the first 24 hours, in small lesions confined to the grey or subcortical white matter and in infratentorial ischemic lesion. On the other hand, only CT was able to show fresh hemorrhage, although MRI was the method of choice to demonstrate old blood collections. To characterise the follow up of an infarct, CT and MRI were similar, except the marginal contrast enhancement sometimes demonstrated by CT studies between the 2nd and 4th week after stroke event. PET was inferior to show details because of its poorer spatial resolution, but anyhow had a high sensitivity and provided additional informations concerning secondary inactivations of brain areas not directly damaged. Additionally PET was able to demonstrate areas of anaerobic glycolysis and lesions of diminished glucose utilisation in TIAs. Small areas of gliosis in the white matter of the cerebral hemispheres were frequently found in patients with cerebro-vascular diseases; they were best shown by MRI, but do not correlate with the extent of vascular stenoses or occlusions, shown by angiography. (orig) [de

  19. Imaging of ischemic heart disease

    International Nuclear Information System (INIS)

    Lipton, Martin J.; Reba, Richard C.; Bogaert, Jan; Boxt, Larry M.

    2002-01-01

    Despite advances in the understanding and treatment of ischemic cardiomyopathy, characterized by extensive coronary artery disease and left ventricular (LV) dysfunction, the prognosis remains poor with only a 50-60% 5-year survival rate. The composition of atherosclerotic lesions is currently regarded as being more important than the degree of stenosis in determining acute events. If imaging techniques could distinguish vulnerable from stable plaques, then high-risk patient subgroups could be identified. Another important concept is that LV dysfunction may be the result of either scarring due to necrosis or to the presence of myocardial hibernation, in which there is sufficient blood flow to sustain viable myocytes, but insufficient to maintain systolic contraction. This concept of myocardial viability is critical for making optimal clinical management decisions. This review describes how noninvasive imaging methods can be used to distinguish regions of irreversibly injured myocardium from viable but hibernating segments. Technical advances in CT and MR have made imaging of the beating heart possible. Considerable clinical progress has already been made and further cardiac applications are expected. Radiologists therefore have new opportunities for involvement in cardiac imaging but must recognize the political implications as well as the diagnostic potential of these modalities not only for the heart, but also for the whole vascular system. This review focuses on imaging myocardial injury. It compares state-of-the-art CT and MR with more established yet contemporary echocardiography and nuclear scintigraphy. (orig.)

  20. Smoking Cessation Intervention After Ischemic Stroke or Transient Ischemic Attack. A Randomized Controlled Pilot Trial

    DEFF Research Database (Denmark)

    Brunner Frandsen, Nicole; Sørensen, Margit; Hyldahl, Tanja Kirstine

    2012-01-01

    BACKGROUND: Smoking cessation is widely recommended for secondary stroke prevention. However, little is known about the efficacy of smoking cessation intervention after stroke or transient ischemic attack (TIA). METHODS: Ninety-four smokers under age 76, admitted with ischemic stroke or TIA were ...

  1. Quantitative Measurement of Physical Activity in Acute Ischemic Stroke and Transient Ischemic Attack

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2014-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to quantitatively measure and describe the amount and pattern of physical activity in patients within the first week after acute ischemic stroke and transient ischemic attack using accelerometers. METHODS: A total of 100 patients with acute is...

  2. Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

    NARCIS (Netherlands)

    S. Fonville (Susanne); H.M. den Hertog (Heleen); A.A.M. Zandbergen (Adrienne); P.J. Koudstaal (Peter Jan); H.F. Lingsma (Hester)

    2014-01-01

    textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing

  3. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    Science.gov (United States)

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. [Surgery of refractory ischemic arrhythmia].

    Science.gov (United States)

    Viganò, M; Graffigna, A; Salerno, G

    1992-03-01

    Since June 1980, 138 patients have undergone surgical treatment for refractory ventricular tachycardia due to ischemic heart disease. Electrically guided surgical ablation (EGSA) of the focus was performed in 117 patients, while 14 patients underwent application of automatic implantable cardioverter-defibrillator (AICD), and 8 patients underwent heart transplantation. During the whole period considered, among the EGSA patients an operative mortality of 13 patients was observed (11.4%), with a late mortality of another 14 patients (13.4%). Two early and six late recurrences were described, and 4 cases of sudden or unexplained death, with 2 cases clearly due to an arrhythmic event. Multivariate analysis showed preoperative ejection fraction lower than 25% as a powerful predictor of early mortality (32% vs 0%). Actuarial survival rate of patients with LVEF lower than 25% was 67 +/- 12% vs 95 +/- 2% at one year and 37 +/- 25% vs 94 +/- 8% at 8 years. A high operative mortality was then observed in patients who underwent aneurysmectomy alone or visually guided procedures as compared to electrically guided procedures (75% or 3 deaths out of 4 patients vs 8.5% or 10 out of 113 patients, respectively). Patients who received an AICD with or without associated procedures showed 1 case of in-hospital mortality and no late mortality; in 6 patients at least one shock was delivered; in two patients the AICD was implanted during an EGSA procedure, due to multiple or difficult origins of the arrhythmias. Of patients who underwent heart transplantation one case of later mortality was observed due to malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Ischemic Tolerance of the Brain and Spinal Cord: A Review.

    Science.gov (United States)

    Yunoki, Masatoshi; Kanda, Takahiro; Suzuki, Kenta; Uneda, Atsuhito; Hirashita, Koji; Yoshino, Kimihiro

    2017-11-15

    Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

  6. The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

    Science.gov (United States)

    Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

    2018-04-23

    Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

  7. Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

    Science.gov (United States)

    Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

    2015-10-22

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Herbal Medicine in Ischemic Stroke: Challenges and Prospective.

    Science.gov (United States)

    Gaire, Bhakta Prasad

    2018-04-01

    Herbal medicines, mainly of plant source, are invaluable source for the discovery of new therapeutic agents for all sorts of human ailments. The complex pathogenesis of stroke and multifactorial effect of herbal medicine and their active constituents may suggest the promising future of natural medicine for stroke treatment. Anti-oxidant, anti-inflammatory, anti-apoptotic, neuroprotective and vascular protective effect of herbal medicines are believed to be efficacious in stroke treatment. Herbs typically have fewer reported side effects than allopathic medicine, and may be safer to use over longer period of time. Herbal medicines are believed to be more effective for the longstanding health complaints, such as stroke. Several medicinal plants and their active constituents show the promising results in laboratory research. However failure in transformation of laboratory animal research to the clinical trials has created huge challenge for the use of herbal medicine in stroke. Until and unless scientifically comprehensive evidence of the efficacy and safety of herbal medicine in ischemic stroke patients is available, efforts should be made to continue implementing treatment strategies of proven effectiveness. More consideration should be paid to natural compounds that can have extensive therapeutic time windows, perfect pharmacological targets with few side effects. Herbal medicine has excellent prospective for the treatment of ischemic stroke, but a lot of effort should be invested to transform the success of animal research to human use.

  9. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhao [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States); Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC

  10. Infection in the ischemic lower extremity.

    Science.gov (United States)

    Fry, D E; Marek, J M; Langsfeld, M

    1998-06-01

    Infections in the lower extremity of the patient with ischemia can cover a broad spectrum of different diseases. An understanding of the particular pathophysiologic circumstances in the ischemic extremity can be of great value in understanding the natural history of the disease and the potential complications that may occur. Optimizing blood flow to the extremity by using revascularization techniques is important for any patient with an ischemic lower extremity complicated by infection or ulceration. Infections in the ischemic lower extremity require local débridement and systemic antibiotics. For severe infections, such as necrotizing fasciitis or the fetid foot, more extensive local débridement and even amputation may be required. Fundamentals of managing prosthetic graft infection require removing the infected prosthesis, local wound débridement, and systemic antibiotics while attempting to preserve viability of the lower extremity using autogenous graft reconstruction.

  11. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  12. Polymorphisms in apolipoprotein B and risk of ischemic stroke

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov

    2007-01-01

    Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

  13. [Nonfasting triglycerides and risk of ischemic stroke--secondary publication

    DEFF Research Database (Denmark)

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Jensen, J.S.

    2009-01-01

    The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...... hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level triglycerides is associated with risk of ischemic stroke Udgivelsesdato...

  14. Ischemic stroke destabilizes circadian rhythms

    Directory of Open Access Journals (Sweden)

    Borjigin Jimo

    2008-10-01

    Full Text Available Abstract Background The central circadian pacemaker is a remarkably robust regulator of daily rhythmic variations of cardiovascular, endocrine, and neural physiology. Environmental lighting conditions are powerful modulators of circadian rhythms, but regulation of circadian rhythms by disease states is less clear. Here, we examine the effect of ischemic stroke on circadian rhythms in rats using high-resolution pineal microdialysis. Methods Rats were housed in LD 12:12 h conditions and monitored by pineal microdialysis to determine baseline melatonin timing profiles. After demonstration that the circadian expression of melatonin was at steady state, rats were subjected to experimental stroke using two-hour intralumenal filament occlusion of the middle cerebral artery. The animals were returned to their cages, and melatonin monitoring was resumed. The timing of onset, offset, and duration of melatonin secretion were calculated before and after stroke to determine changes in circadian rhythms of melatonin secretion. At the end of the monitoring period, brains were analyzed to determine infarct volume. Results Rats demonstrated immediate shifts in melatonin timing after stroke. We observed a broad range of perturbations in melatonin timing in subsequent days, with rats exhibiting onset/offset patterns which included: advance/advance, advance/delay, delay/advance, and delay/delay. Melatonin rhythms displayed prolonged instability several days after stroke, with a majority of rats showing a day-to-day alternation between advance and delay in melatonin onset and duration. Duration of melatonin secretion changed in response to stroke, and this change was strongly determined by the shift in melatonin onset time. There was no correlation between infarct size and the direction or amplitude of melatonin phase shifting. Conclusion This is the first demonstration that stroke induces immediate changes in the timing of pineal melatonin secretion, indicating

  15. Neonatal ischemic brain injury: what every radiologist needs to know

    International Nuclear Information System (INIS)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E.

    2012-01-01

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  16. The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic ...

    African Journals Online (AJOL)

    The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic Stroke In Animal Model: A Review. ... Conclusion: An awareness of the benefits of acupuncture might lead more patients into accepting acupuncture therapy for the management of patients with ischemic stroke and patients with high risk of ischemic stroke.

  17. Effects of ischemic preconditioning associated to different preservation solutions in protecting the intestinal graft Efeitos do precondicionamento isquêmico associado a diferentes soluções de preservação na proteção do enxerto intestinal

    Directory of Open Access Journals (Sweden)

    José de Souza Neves

    2011-10-01

    Full Text Available PURPOSE: To evaluate the effects of ischemic preconditioning (IPC associate with different preservation solutions, in the protecting of gut. METHODS: Four groups of 14 rats underwent laparotomy and collecting 20 cm of ileum, for preservation, at 4ºC, in Belzer (Belz, Ringer (RL, Celsior (Cs and Custodiol (Cust solutions, for 24 hours. Prior to collection, half of the animals in each group were subjected to IPC. During preservation, in the periods of zero, 12, 18 and 24 hours, were conducted evaluating the degree of mucosal injury and dosage of malondialdehyde acid (MDA. RESULTS: In all periods the RL group, with and without IPC, presented MDA values higher than the Belz and Cs. The degree of mucosal injury in the non-ipc RLgroup with 12h preservation was higher than the others; with 18 and 24h, the RL and Cust had higher degrees of damage than Cs and Belz. With IPC, in all periods, the group Cs and Belz had lower degrees of injury. CONCLUSION: The Celsior and Belzer solutions had better protective effects on the gut and these effects were enhanced by IPC.OBJETIVO: Avaliar os efeitos do precondicionamento isquêmico (PCI associado a diferentes soluções de preservação, na proteção do intestino delgado. MÉTODOS: Quatro grupos de 14 ratos Wistar, foram submetidos à laparotomia e coleta de 20 cm de íleo, para preservação, a 4ºC, nas soluções de Belzer (Belz, Ringer (RL, Celsior (Cs e Custodiol (Cust por 24 horas. Previamente à coleta, em metade dos animais de cada grupo, o intestino foi submetido ao PCI. Durante a preservação, nos períodos de Zero, 12, 18 e 24 horas, foram realizados avaliação do grau de lesão da mucosa e dosagem do ácido malondialdeído (MDA. RESULTADOS: Em todos os períodos o grupo RL, sem e com pci, apresentou valores maiores de MDA do que o Belz e Cs. O grau de lesão da mucosa nos grupos sem pci com preservação de 12h, no grupo RL, foi maior que nos demais; com 18h e 24h o grupo RL e Cust apresentaram

  18. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Sillesen, Henrik

    2003-01-01

    Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.......Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity....

  19. DNA damage response in nephrotoxic and ischemic kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Mingjuan; Tang, Chengyuan [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Ma, Zhengwei [Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States); Huang, Shuang [Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL (United States); Dong, Zheng, E-mail: zdong@augusta.edu [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States)

    2016-12-15

    DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore relies on a thorough elucidation of the DDR pathways in various forms of AKI.

  20. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

    Directory of Open Access Journals (Sweden)

    Ahmad Sukari Halim

    2013-11-01

    Full Text Available BackgroundIschemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published.MethodsSixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed.ResultsThe results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups.ConclusionsIn conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts.

  1. Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

    OpenAIRE

    Fonville, Susanne; Hertog, Heleen; Zandbergen, Adrienne; Koudstaal, Peter Jan; Lingsma, Hester

    2014-01-01

    textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to...

  2. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes.

    Science.gov (United States)

    Perna, Robert; Temple, Jessica

    2015-01-01

    Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n = 172) or hemorrhagic stroke (n = 112) within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4) at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

  3. Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes

    Directory of Open Access Journals (Sweden)

    Robert Perna

    2015-01-01

    Full Text Available Background. Ischemic and hemorrhagic strokes have different pathophysiologies and possibly different long-term cerebral and functional implications. Hemorrhagic strokes expose the brain to irritating effects of blood and ischemic strokes reflect localized or diffuse cerebral vascular pathology. Methods. Participants were individuals who suffered either an ischemic (n=172 or hemorrhagic stroke (n=112 within the past six months and were involved in a postacute neurorehabilitation program. Participants completed three months of postacute neurorehabilitation and the Mayo Portland Adaptability Inventory-4 (MPAI-4 at admission and discharge. Admission MPAI-4 scores and level of functioning were comparable. Results. Group ANOVA comparisons show no significant group differences at admission or discharge or difference in change scores. Both groups showed considerably reduced levels of productivity/employment after discharge as compared to preinjury levels. Conclusions. Though the pathophysiology of these types of strokes is different, both ultimately result in ischemic injuries, possibly accounting for lack of findings of differences between groups. In the present study, participants in both groups experienced similar functional levels across all three MPAI-4 domains both at admission and discharge. Limitations of this study include a highly educated sample and few outcome measures.

  4. Ischemic Stroke during Pregnancy and Puerperium

    Directory of Open Access Journals (Sweden)

    Elisabetta Del Zotto

    2011-01-01

    Full Text Available Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy.

  5. Short Telomere Length and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Madrid, Alexander Scheller; Rode, Line; Nordestgaard, Børge Grønne

    2016-01-01

    are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding. METHODS: We genotyped 3 genetic variants in OBFC1 (oligonucleotide/oligosaccharide binding fold containing 1), TERT (telomerase reverse transcriptase), and TERC...

  6. Colonic ischemic necrosis following therapeutic embolization

    International Nuclear Information System (INIS)

    Shenoy, S.S.; Satchidanand, S.; Wesp, E.H.; State Univ. of New York, Buffalo

    1981-01-01

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding. (orig.)

  7. CT diagnosis of hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhao Xiang; Ma Jiwei; Wu Lide

    2004-01-01

    Objective: To explore CT characteristics of hypoxic ischemic encephalopathy (HIE), and to improve the accuracy of CT diagnosis. Methods: 50 cases of neonatal asphyxia in perinatal period diagnosed as hypoxic ischemic encephalopathy by CT was analyzed. Results: The main manifestation of hypoxic ischemic encephalopathy is cerebral edema and intracranial hemorrhage. Focal or diffuse hypo-dense lesion and hyper-dense area in various location and morphology were seen on CT images. (1) Localized diffuse hypo-dense area in 1 or 2 cerebral lobe were found in 17 cases, and the lesions were localized in frontal lobe (n=6), in frontotemporal lobe (n=5), and in temporo-occipital lobe (n=6). (2) Hypo-density region involving more than three cerebral lobes were found in 18 cases, and abnormalities were found in frontotemporal and parietal lobe (n=8), accompanying with subarachnoid hemorrhage (n=2); in frontal, temporal and occipital lobe (n=6), in which cerebral hemorrhage was complicated (n=1); and in other cerebral lobe (n=4). (3) Diffuse low-density region in all cerebral lobe were found in 15 cases, in which subarachnoid hemorrhage was complicated in 4 cases, and ventricular hemorrhage was found in 2 case. Conclusion: CT imaging plays an important role in diagnosis of hypoxic ischemic encephalopathy and has shown its clinical value

  8. Colonic ischemic necrosis following therapeutic embolization

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, S S; Satchidanand, S; Wesp, E H

    1981-07-15

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding.

  9. Radiopharmaceuticals for diagnosis of ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Komarek, P; Chalabala, M [Institut pro Dalsi Vzdelavani Lekaru a Farmaceutu, Prague (Czechoslovakia)

    1982-01-01

    Radiopharmaceuticals used for diagnosing ischemic heart disease in the experimental and clinical practice are reviewed. The mechanism of their retention by the heart muscle is briefly described. The respective radiopharmaceuticals are divided into preparations imaging disorders in the blood supply of the cardiac muscle, diagnosing the myocardial infarction, and evaluating the contractility of the heart.

  10. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

  11. Magnetic resonance imaging in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Kouichi [Mito Red Cross Hospital (Japan)

    2000-01-01

    This paper summarizes current MRI technology used in the diagnosis of acute cerebral infarction and discusses tasks for further improvement of MRI technology. First, the principles and methods of MRI imaging are described in terms of 1) diffusion-weighted imaging (DWI) and ADC maps, 2) perfusion imaging, 3) the fluid-attenuated inversion recovery (FLAIR) method, and 4) MR angiography (MRA). Then, the actual use of MRI in the early phase of ischemic cerebrovascular disorders is discussed focusing on general MRI procedures, cases in which an ischemic lesion dose not yield a high signal with DWI in the acute phase, and chronological changes in DWI signal strength and ADC. Third, chronological changes in acute cerebrovascular disorder in an animal model of local cerebral ischemia are summarized in terms of expansion of reduced ADC areas and ischemic penumbras in the acute phase of cerebral ischemia. Finally, chronological changes in acute ischemic disorders in patients with cerebrovascular disorders are assessed by reviewing the development of reduced ADC and expansion of DWI lesions. Whether MRI can identify cerebral tissues that can be rescued by the reperfusion method by examining the mismatchs between perfusion images and DWI, relative CBV, and ADC is also discussed. (K.H.)

  12. Rationale for ischemic conditioning to prevent stroke in patients with intracranial arterial stenosis

    Directory of Open Access Journals (Sweden)

    Sami Al Kasab

    2016-01-01

    Full Text Available Intracranial atherosclerotic arterial stenosis (ICAS is one of the most common causes of stroke worldwide and is associated with particularly a high risk of recurrent stroke. Although aggressive medical management, consisting of dual antiplatelet therapy and intensive control of vascular risk factors, has improved the prognosis of patients with ICAS, subgroups of patients remain at very high risk of stroke. More effective therapies for these high-risk patients are urgently needed. One promising treatment is remote limb ischemic conditioning, which involves producing repetitive, transient ischemia of a limb by inflating a blood pressure cuff with the intention of protecting the brain from subsequent ischemia. In this study, we review the limitations of currently available treatments, discuss the potential mechanisms of action of ischemic conditioning, describe the preclinical and clinical data suggesting a possible role of ischemic conditioning in treating patients with ICAS, and outline the questions that still need to be answered in future studies of ischemic conditioning in subjects with ICAS.

  13. Klotho upregulation contributes to the neuroprotection of ligustilide against cerebral ischemic injury in mice.

    Science.gov (United States)

    Long, Fang-Yi; Shi, Meng-Qi; Zhou, Hong-Jing; Liu, Dong-Ling; Sang, Na; Du, Jun-Rong

    2018-02-05

    Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms. Administration of ligustilide prevented the development of neurological deficits and reduced neuronal loss in the hippocampal CA1 region and the caudate putamen after cerebral ischemia. The protective effects were associated with inhibition of the RIG-I/NF-κB p65 and Akt/FoxO1 pathways and with prevention of inflammation and oxidative stress in the brain. Further, downregulation of klotho could attenuate the neuroprotection of ligustilide against cerebral ischemic injury. Ligustilide exerted neuroprotective effects in mice after cerebral ischemia by regulating anti-inflammatory and anti-oxidant signaling pathways. Furthermore, klotho upregulation contributes to the neuroprotection of LIG against cerebral ischemic injury. These results indicated that ligustilide may be a promising therapeutic agent for the treatment of cerebral ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cocktail treatment, a promising strategy to treat acute cerebral ischemic stroke?

    Directory of Open Access Journals (Sweden)

    Li-jun Liang

    2016-01-01

    Full Text Available Up to now, over 1,000 experimental treatments found in cells and rodents have been difficult to translate to human ischemic stroke. Since ischemia and reperfusion, two separate stages of ischemic stroke, have different pathophysiological mechanisms leading to brain injury, a combination of protective agents targeting ischemia and reperfusion respectively may obtain substantially better results than a single agent. Normobaric hyperoxia (NBO has been shown to exhibit neuro- and vaso-protective effects by improving tissue oxygenation when it is given during ischemia, however the effect of NBO would diminish when the duration of ischemia and reperfusion was extended. Therefore, during reperfusion drug treatment targeting inflammation, oxidative stress and free radical scavenger would be a useful adjuvant to extend the therapeutic window of tissue plasminogen activator, the only United States Food and Drug Administration (FDA approved treatment for acute ischemic stroke. In this review, we discussed the neuro- and vaso-protective effects of NBO and recent finding of combining NBO with other drugs.

  15. CT findings in isolated ischemic proctosigmoiditis

    International Nuclear Information System (INIS)

    Wiesner, Walter; Mortele, Koenraad J.; Ji, Hoon; Khurana, Bharti; Ros, Pablo R.; Glickman, Jonathan N.

    2002-01-01

    The purpose of our study was to describe the CT features of ischemic proctosigmoiditis in correlation with clinical, laboratory, endoscopic, and histopathologic findings. Our study included seven patients with isolated ischemic proctosigmoiditis. Patients were identified by a retrospective review of all histopathologic records of colonoscopic biopsies performed during a time period of 4 years. All patients presented with left lower abdominal quadrant pain, bloody stools, and leukocytosis, and four patients had fever at the time of presentation. Four of seven patients suffered from diarrhea, one of seven was constipated and two of seven had normal stool consistency. The CT examinations were reviewed by two authors by consensus and compared with clinical and histopathologic results as well as with the initial CT diagnosis. The CT showed a wall thickening confined to the rectum and sigmoid colon in seven of seven patients, stranding of the pararectal fat in four of seven, and stranding of the perisigmoidal fat in one of seven patients. There were no enlarged lymph nodes, but five of seven patients showed coexistent diverticulosis and in three of these patients CT findings were initially misinterpreted as sigmoid diverticulitis. Endoscopies and histopathologic analyses of endoscopic biopsies confirmed non-transmural ischemic proctosigmoiditis in all patients. Isolated ischemic proctosigmoiditis often presents with unspecific CT features and potentially misleading clinical and laboratory findings. In an elderly patient or a patient with known cardiovascular risk factors the diagnosis of ischemic proctosigmoiditis should be considered when wall thickening confined to the rectum and sigmoid colon is seen that is associated with perirectal fat stranding. (orig.)

  16. Usefulness of colonoscopy in ischemic colitis.

    Science.gov (United States)

    Lozano-Maya, M; Ponferrada-Díaz, A; González-Asanza, C; Nogales-Rincón, O; Senent-Sánchez, C; Pérez-de-Ayala, V; Jiménez-Aleixandre, P; Cos-Arregui, E; Menchén-Fernández-Pacheco, P

    2010-07-01

    the ischemic colitis is intestinal the most frequent cause of ischemia. With this work we determine the demographic and clinical characteristics, and the usefulness of the colonoscopy in the patients with ischemic colitis diagnosed in our centre in relation to a change of therapeutic attitude. retrospective study in which were selected 112 patients diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five years. It was analyzed: age, sex, reason for examination, factors of cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic attitude, treatment and outcome. the average age was of 73.64 + or - 12.10 years with an equal incidence in women (50.9%) and the men (49.1%). The associated factors were the HTA (61.1%), tobacco (37.2%) and antecedents of cardiovascular episode (52.2%). The most frequent reason for colonoscopy was rectorrhagia (53.6%) followed of the abdominal pain (30.4%), being urgent the 65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50 increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The serious ischemic colitis (25%) was more frequent in men (64.3%) in urgent indication (85.71%) and attends with high mortality (53.57%). Surgical treatment in the 57.14% was made with a good evolution in the 50%, whereas the patients with mild or moderate ischemic colitis had a better prognosis (favourable evolution in 80.95%) with smaller requirement of the surgical treatment (4.76%), p change of attitude according to the result of the same one. The evidence of a serious colitis supposed an increase of the necessity of surgery and worse prognosis.

  17. [Cerebral protection].

    Science.gov (United States)

    Cattaneo, A D

    1993-09-01

    Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

  18. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    International Nuclear Information System (INIS)

    Xia, D.Y.; Li, W.; Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K.

    2013-01-01

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis

  19. Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

    Science.gov (United States)

    Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

    2016-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

  20. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y. [Department of Neurology, Navy General Hospital of PLA, Beijing (China); Li, W. [General Hospital of Shenyang Military Command, Department of Neurology, Shenyang, China, Department of Neurology, General Hospital of Shenyang Military Command, Shenyang (China); Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K. [Department of Neurology, Navy General Hospital of PLA, Beijing (China)

    2013-08-10

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  1. Reconsideration of Secondary Risk Management Strategies in Patients with Ischemic Heart Disease.

    Science.gov (United States)

    Kashiyama, Kuninobu; Sonoda, Shinjo; Otsuji, Yutaka

    2017-01-01

    The main risk factors in ischemic heart diseases, including myocardial infarction, are hypertension, dyslipidemia, diabetes, obesity and smoking. The incidence of ischemic heart disease in Japan has been lower than that in Western countries because of differences in lifestyle and the anatomy of the coronary arteries, but the situation has been changing recently because of the westernization of lifestyle. Cardiovascular diseases have become the second most common cause of death in Japan, and 40% of those deaths are attributed to ischemic heart disease. Patients with a history of myocardial infarction, especially, have an increased risk of re-infarction, so strict management of coronary risk factors is important for the prevention of secondary ischemic heart disease. Although there are many guidelines about how to manage the risk factors, there are still many problems. Although lipid management has been demonstrated to have a protective effect against coronary artery disease and arteriosclerotic guidelines have been developed, it is reported that only about one third of patients achieved the low-density lipoprotein (LDL) target value under secondary prevention. Moreover, it is unclear whether the lower target value is required for high-risk patients. Recent research on diabetes has reported increased mortality in patients with intensive glycemic control. We should discuss when to start treatment, which medicine to use, and to what extent we should manage glycemic control. Strict management based on current therapeutic guidelines is effective for secondary prevention of ischemic heart disease, with target values of less than 135/85 mmHg for home blood pressure, less than 100 mg/dl for LDL-C, more than 40 mg/dl for HDL-C, less than 150 mg/dl for TG, and, for diabetic patients, less than 7.0% for HbA1c (NGSP).

  2. Acute kidney injury and edaravone in acute ischemic stroke: the Fukuoka Stroke Registry.

    Science.gov (United States)

    Kamouchi, Masahiro; Sakai, Hironori; Kiyohara, Yutaka; Minematsu, Kazuo; Hayashi, Kunihiko; Kitazono, Takanari

    2013-11-01

    A free radical scavenger, edaravone, which has been used for the treatment of ischemic stroke, was reported to cause acute kidney injury (AKI) as a fatal adverse event. The aim of the present study was to clarify whether edaravone is associated with AKI in patients with acute ischemic stroke. From the Fukuoka Stroke Registry database, 5689 consecutive patients with acute ischemic stroke who were hospitalized within 24 hours of the onset of symptoms were included in this study. A logistic regression analysis for the Fukuoka Stroke Registry cohort was done to identify the predictors for AKI. A propensity score-matched nested case-control study was also performed to elucidate any association between AKI and edaravone. Acute kidney injury occurred in 128 of 5689 patients (2.2%) with acute ischemic stroke. A multivariate analysis revealed that the stroke subtype, the basal serum creatinine level, and the presence of infectious complications on admission were each predictors of developing AKI. In contrast, a free radical scavenger, edaravone, reduced the risk of developing AKI (multivariate-adjusted odds ratio [OR] .45, 95% confidence interval [CI] .30-.67). Propensity score-matched case-control study confirmed that edaravone use was negatively associated with AKI (propensity score-adjusted OR .46, 95% CI .29-.74). Although AKI has a significant impact on the clinical outcome of hospital inpatients, edaravone has a protective effect against the development of AKI in patients with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  4. 3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

    Science.gov (United States)

    Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

    2017-05-01

    Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Ischemic stroke: carotid and vertebral artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, P.; Goulao, A. [Hospital Garcia de Orta, Servico de Neurorradiologia, Almada (Portugal)

    2005-03-01

    Ischemic strokes may have distinct aetiologies, including several different intrinsic arterial pathological disorders. The diagnosis and understanding of these arterial diseases is critical for the correct management of stroke as different treatment approaches are undertaken according to the aetiology. Atherosclerosis is by far the most common arterial disease among adults, and other pathological processes include arterial dissection, small vessel disease, inflammatory and non-inflammatory vasculopathy and vasomotor disorders. In children, there are several vasculopathies responsible for vaso-occlusive disease such as sickle-cell anemia, acute regressive angiopathy and Moya-Moya disease, neurofibromatosis, dissections, vasculitis associated with intracranial and systemic infections. An overview of the major carotid and vertebral pathological diseases responsible for ischemic stroke in adults and children, highlighting the accuracy of the different imaging modalities for its diagnosis and the imaging appearance of these diseases, is given. (orig.)

  6. Ischemic Stroke: Advances in Diagnosis and Management.

    Science.gov (United States)

    Cassella, Courtney R; Jagoda, Andy

    2017-11-01

    Acute ischemic stroke carries the risk of morbidity and mortality. Since the advent of intravenous thrombolysis, there have been improvements in stroke care and functional outcomes. Studies of populations once excluded from thrombolysis have begun to elucidate candidates who might benefit and thus should be engaged in the process of shared decision-making. Imaging is evolving to better target the ischemic penumbra salvageable with prompt reperfusion. Availability and use of computed tomography angiography identifies large-vessel occlusions, and new-generation endovascular therapy devices are improving outcomes in these patients. With this progress in stroke treatment, risk stratification tools and shared decision-making are fundamental. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Sickle cell-induced ischemic colitis.

    Science.gov (United States)

    Stewart, Camille L; Ménard, Geraldine E

    2009-07-01

    Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

  8. Isolated naratriptan-associated ischemic colitis

    Science.gov (United States)

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  9. Ischemic stroke: carotid and vertebral artery disease

    International Nuclear Information System (INIS)

    Vilela, P.; Goulao, A.

    2005-01-01

    Ischemic strokes may have distinct aetiologies, including several different intrinsic arterial pathological disorders. The diagnosis and understanding of these arterial diseases is critical for the correct management of stroke as different treatment approaches are undertaken according to the aetiology. Atherosclerosis is by far the most common arterial disease among adults, and other pathological processes include arterial dissection, small vessel disease, inflammatory and non-inflammatory vasculopathy and vasomotor disorders. In children, there are several vasculopathies responsible for vaso-occlusive disease such as sickle-cell anemia, acute regressive angiopathy and Moya-Moya disease, neurofibromatosis, dissections, vasculitis associated with intracranial and systemic infections. An overview of the major carotid and vertebral pathological diseases responsible for ischemic stroke in adults and children, highlighting the accuracy of the different imaging modalities for its diagnosis and the imaging appearance of these diseases, is given. (orig.)

  10. Ischemic Colitis after Weight-Loss Medication

    Directory of Open Access Journals (Sweden)

    Dan Comay

    2003-01-01

    Full Text Available BACKGROUND: Previous weight-loss medications have received cautious support due to their association with pulmonary hypertension and valvular heart disease. However, newer drugs are increasingly being recommended as potentially safer and more efficacious. We report a case of ischemic colitis possibly linked to the use of a weight-loss drug, and review the literature to highlight an important latent consequence of these medications.

  11. Stem cell therapy for ischemic heart diseases.

    Science.gov (United States)

    Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

    2017-01-01

    Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. Ischemic Colitis in an Endurance Runner

    Directory of Open Access Journals (Sweden)

    Chase Grames

    2012-01-01

    Full Text Available A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options.

  13. NADPH Oxidase, NOX1, Mediates Vascular Injury in Ischemic Retinopathy

    Science.gov (United States)

    Deliyanti, Devy; Rana, Indrajeetsinh; Miller, Antonia G.; Agrotis, Alex; Armani, Roksana; Szyndralewiez, Cédric; Wingler, Kirstin; Touyz, Rhian M.; Cooper, Mark E.; Jandeleit-Dahm, Karin A.; Schmidt, Harald H.H.W.

    2014-01-01

    Abstract Aims: Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. Results: Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. Innovation: Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. Conclusions: Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathies. Antioxid. Redox Signal. 20, 2726–2740. PMID:24053718

  14. TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    V. V. Kalyuzhin

    2014-01-01

    Full Text Available The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: ischō, meaning to hold back, and haima, meaning blood - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic and lusitropic (diastolic function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints. It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.

  15. Refining the ischemic penumbra with topography.

    Science.gov (United States)

    Thirugnanachandran, Tharani; Ma, Henry; Singhal, Shaloo; Slater, Lee-Anne; Davis, Stephen M; Donnan, Geoffrey A; Phan, Thanh

    2018-04-01

    It has been 40 years since the ischemic penumbra was first conceptualized through work on animal models. The topography of penumbra has been portrayed as an infarcted core surrounded by penumbral tissue and an extreme rim of oligemic tissue. This picture has been used in many review articles and textbooks before the advent of modern imaging. In this paper, we review our understanding of the topography of the ischemic penumbra from the initial experimental animal models to current developments with neuroimaging which have helped to further define the temporal and spatial evolution of the penumbra and refine our knowledge. The concept of the penumbra has been successfully applied in clinical trials of endovascular therapies with a time window as long as 24 h from onset. Further, there are reports of "good" outcome even in patients with a large ischemic core. This latter observation of good outcome despite having a large core requires an understanding of the topography of the penumbra and the function of the infarcted regions. It is proposed that future research in this area takes departure from a time-dependent approach to a more individualized tissue and location-based approach.

  16. ACE Gene in Egyptian Ischemic Stroke Patients.

    Science.gov (United States)

    Mostafa, Magdy A; El-Nabiel, Lobna M; Fahmy, Nagia Aly; Aref, Hany; Shreef, Edrees; Abd El-Tawab, Fathy; Abdulghany, Osama M

    2016-09-01

    Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. [Ischemic stroke in the young adult].

    Science.gov (United States)

    Calvet, D

    2016-01-01

    Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. Hypercholesterolemia in patients of ischemic stroke

    International Nuclear Information System (INIS)

    Saeed, E.; Ali, R.; Din, M.J.U.; Saeed, A.; Jadoon, R.J.

    2015-01-01

    Background: Stroke is a common neurological disease that results in significant mortality and morbidity globally. Several risk factors have been identified for stroke among which hyperlipidaemia is one of the modifiable risk factors. Recent clinical trials have shown a reduction in ischemic stroke for patients taking lipid lowering medications. Therefore, the aim of this study was to find out the frequency of hypercholesterolemia in patients of ischemic stroke in Hazara region. Method: This cross sectional study was carried out in the Medical Department of Ayub Teaching Hospital, Abbottabad. Ninety patients of stroke confirmed as ischemic by CT scan brain were enrolled in the study after informed consent. The frequency of hypercholesterolemia in patients was recorded. Results: There were 55 (61.1 percentage) males. The mean age of patients was 64.4±11.5 years. The mean serum cholesterol in all patients was 4.16±1.1 mmol/l. The mean serum cholesterol of male patients was 4.3±1.2 mmol/l and 4.0±10.9 mmol/l in the case of females. Conclusions: Hypercholesterolemia could not be established as a major risk factor for stroke in our setup through this study that allude to the fact that other risk factors might be contributing more to the incidence of cerebrovascular accident in our population. (author)

  19. Current status and outlook of endovascular therapy for cerebral ischemic diseases

    International Nuclear Information System (INIS)

    Li Minghua; Zhao Jungong

    2005-01-01

    Improvement of diagnostic technology and increasing advent of new materials for intervention has created a new area for endovascular therapy of cerebral ischemic diseases. Current research findings have shown that endovascular thrombolysis in acute stage of cerebral infarction can accelerate the rate of re-canalization of occluded arteries and greatly decrease the morbidity and mortality of cerebral ischemic vascular diseases. Stenting of arterial stenosis can the improve of blood supply distal to the lesion, prevent recurrent cerebral ischemic stroke. As a result, endovascular thrombolysis for acute cerebral infarction and stenting for intracranial and carotid arterial stenosis are booming both at home and abroad. Proper selection of patients of acute cerebral infarction for endovascular thrombolysis with less complications could be achieved through CT perfusion, MR perfusion-weighted image (PWI) and diffusion-weighted image (DWI), non-invasive vascular imaging technology including CEMRA and CTA for confirming and demonstrating the sites and causes of cerebral ischemia, and furthermore for evaluating the survival ability and etc. The research team administered albumin and magnesium sulfate as neurological protection drug to treat rat infarction model within 6 hours of onset resulting with the same effect of decreasing the damage of ischemic cerebral tissue and without hemorrhagic complication. It is certain that hemorrhagic complication in thrombolysis is a result of multiple factors with no single drug being able to solve the problem. It is predictable that, based on semi-quantitative or quantitative parameters of CT or MRI in conjunction with PWI/DWI mismatch model rather than simply on the onset time of infarction for proper selection of patients of cerebral infarction, mechanic thrombus-disruption and/or intra-arterial thrombolysis together with intervention of neurological protection drug will be the trend for treating acute cerebral infarction in the future

  20. New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

    Science.gov (United States)

    Foroozan, Rod

    2017-02-01

    Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Improving the Translation of Animal Ischemic Stroke Studies to Humans

    OpenAIRE

    Jickling, Glen C; Sharp, Frank R

    2014-01-01

    Despite testing more than 1026 therapeutic strategies in models ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendation...

  2. Neonatal ischemic brain injury: what every radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  3. Cardioprotection against experimental myocardial ischemic injury using cornin

    Directory of Open Access Journals (Sweden)

    Y. Xu

    2016-01-01

    Full Text Available Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  4. Effect of melatonin on kidney cold ischemic preservation injury

    Science.gov (United States)

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2nd, 24th, 36th, and 48th hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48th hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID:24179573

  5. Temporal delta wave and ischemic lesions on MRI

    International Nuclear Information System (INIS)

    Inui, Koji; Kawamoto, Hozumi; Kawakita, Masahiko; Wako, Kazuhisa; Nakashima, Hiromichi; Kamihara, Masanori; Nomura, Junichi

    1994-01-01

    The present study was designed to determine the clinical significance of a temporal low-voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain. (author)

  6. Ischemic perinatal brain damage. Neuropathologic and CT correlations

    Energy Technology Data Exchange (ETDEWEB)

    Crisi, G; Mauri, C; Canossi, G; Della Giustina, E

    1986-01-01

    The term ''hypoxic-ischemic encephalopathy'' covers a large part of neonatal neuropathology including the various forms of intracerebral haemorrhage. In the present work the term is confined to ischemic brain edema and actual infarction, be it diffuse or focal. Eighteen newborns with CT evidence of ischemic brain lesions and infarctual necrosis were selected. Emphasis is placed on current data on neuropathology of ischemic brain edema and its CT appearance. Particular entities such as periventricular leukomalacia and multicystic encephalopathy are discussed. Relationship between CT and temporal profile of cerebral damage is emphasized in order to predict the structural sequelae and the longterm prognosis. 31 refs.

  7. Ischemic Preconditioning of One Forearm Enhances Static and Dynamic Apnea

    DEFF Research Database (Denmark)

    Kjeld, Thomas; Rasmussen, Mads Reinholdt; Jattu, Timo

    2014-01-01

    INTRODUCTION: Ischemic preconditioning enhances ergometer cycling and swimming performance. We evaluated whether ischemic preconditioning of one forearm (four times for 5 min) also affects static breath hold and underwater swimming, whereas the effect of similar preconditioning on ergometer rowing...... preconditioning reduced the forearm oxygen saturation from 65% ± 7% to 19% ± 7% (mean ± SD; P right thigh.......05). CONCLUSIONS: We conclude that while the effect of ischemic preconditioning (of one forearm) on ergometer rowing was minimal, probably because of reduced muscle oxygenation during the warm-up, ischemic preconditioning does enhance both static and dynamic apnea, supporting that muscle ischemia is an important...

  8. Tranexamic Acid Does Not Influence Cardioprotection by Ischemic Preconditioning and Remote Ischemic Preconditioning

    NARCIS (Netherlands)

    van Caster, Patrick; Eiling, Sandra; Boekholt, Yvonne; Behmenburg, Friederike; Dorsch, Marianne; Heinen, André; Hollmann, Markus W.; Huhn, Ragnar

    2018-01-01

    Prior studies have suggested that the antifibrinolytic drug aprotinin increases the infarct size after ischemia and reperfusion (I/R) and attenuates the effect of ischemic preconditioning (IPC). Aprotinin was replaced by tranexamic acid (TXA) in clinical practice. Here, we investigated whether TXA

  9. Cancer in young adults with ischemic stroke.

    Science.gov (United States)

    Aarnio, Karoliina; Joensuu, Heikki; Haapaniemi, Elena; Melkas, Susanna; Kaste, Markku; Tatlisumak, Turgut; Putaala, Jukka

    2015-06-01

    Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke. 1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5-13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan-Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality. One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0-9.5) years and from stroke to poststroke cancer was 6.7 (2.7-10.9) years. Poststroke cancer was associated with age>40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%-85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%-23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators. Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients. © 2015 American Heart Association, Inc.

  10. Structural genomic variation in ischemic stroke

    Science.gov (United States)

    Matarin, Mar; Simon-Sanchez, Javier; Fung, Hon-Chung; Scholz, Sonja; Gibbs, J. Raphael; Hernandez, Dena G.; Crews, Cynthia; Britton, Angela; Wavrant De Vrieze, Fabienne; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Silliman, Scott; Case, L. Douglas; Hardy, John A.; Rich, Stephen S.; Meschia, James F.; Singleton, Andrew B.

    2008-01-01

    Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions;3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study. PMID:18288507

  11. Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

    Science.gov (United States)

    Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

    2017-09-01

    Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Ventricular tachycardia in ischemic heart disease substrates

    Directory of Open Access Journals (Sweden)

    Olujimi A. Ajijola

    2014-01-01

    This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT.

  13. CT fogging effect with ischemic cerebral infarcts

    International Nuclear Information System (INIS)

    Becker, H.; Desch, H.; Hacker, H.; Pencz, A.; Frankfurt Univ.

    1979-01-01

    Systematic CT studies on ten patients with persistent ischemic cerebral infarct revealed a constant phenomenon, the fogging effect. The hypodense infarct at the beginning will be isodense, or close to isodense, on the plain CT during the second or third week and at a later stage will be hypodense again. The fogging infarcted area shows homogeneous intensive contrast enhancement. Knowledge of the fogging effect is important for correct interpretation of the CT image and the indication for contrast medium CT. CT without contrast medium may lead to misinterpretation during the second and third week after the onset of cerebral infarction. (orig.) [de

  14. CT fogging effect with ischemic cerebral infarcts

    Energy Technology Data Exchange (ETDEWEB)

    Becker, H; Desch, H; Hacker, H; Pencz, A [Frankfurt Univ. (Germany, F.R.). Abt. fuer Neurologie; Frankfurt Univ. (Germany, F.R.). Abt. fuer Neuroradiologie)

    1979-01-01

    Systematic CT studies on ten patients with persistent ischemic cerebral infarct revealed a constant phenomenon, the fogging effect. The hypodense infarct at the beginning will be isodense, or close to isodense, on the plain CT during the second or third week and at a later stage will be hypodense again. The fogging infarcted area shows homogeneous intensive contrast enhancement. Knowledge of the fogging effect is important for correct interpretation of the CT image and the indication for contrast medium CT. CT without contrast medium may lead to misinterpretation during the second and third week after the onset of cerebral infarction.

  15. MR of the normal and ischemic hip

    International Nuclear Information System (INIS)

    Mitchell, D.G.

    1988-01-01

    Magnetic resonance imaging (MRI) appears to be more sensitive than traditional radiographic and radionuclide methods for detecting early avascular necrosis (AVN) of the femoral head. The authors have found that in addition to its proven value for early detection, MRI can help us characterize individual lesions and understand the pathophysiology of AVN. This chapter reviews the clinical and pathological features of AVN of the femoral head, and describes recent contributions of MRI toward understanding the normal and ischemic hip. This review summarizes the 5-year experience of the MR group at the Hospital of the University of Pennsylvania

  16. Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis

    Directory of Open Access Journals (Sweden)

    Yuusuke Mitsuka

    2010-07-01

    Full Text Available The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean survival time of 12 months. The initial symptoms are poor and atypical. Because of its rare entity and little knowledge of its treatments, there are few reports of long-term survival. We encountered a very unique case with strong impression on radiological findings of malignant peritoneal methothelioma. We had misdiagnosed it because of the findings and because the time course was similar to that of ischemic colitis. The radiological findings on CT and enema disappeared within one week after antibiotic therapy.

  17. Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China.

    Science.gov (United States)

    Yang, Xiaomeng; Li, Shuya; Zhao, Xingquan; Liu, Liping; Jiang, Yong; Li, Zixiao; Wang, Yilong; Wang, Yongjun

    2017-12-04

    Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF. Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis. Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5), advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI, 1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13), together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were independently associated with newly-detected AF. Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF. NCT02156765 (June 5, 2014).

  18. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis.

    Science.gov (United States)

    Ji, Ruijun; Schwamm, Lee H; Pervez, Muhammad A; Singhal, Aneesh B

    2013-01-01

    Approximately 10% to 14% of ischemic strokes occur in young adults. To investigate the yield of diagnostic tests, neuroimaging findings, and treatment of ischemic strokes in young adults. We retrospectively reviewed data from our Get with the Guidelines-Stroke database from 2005 through 2010. University hospital tertiary stroke center. A total of 215 consecutive inpatients aged 18 to 45 years with ischemic stroke/transient ischemic attack. The mean (SD) age was 37.5 (7) years; 51% were male. There were high incidence rates of hypertension (20%), diabetes mellitus (11%), dyslipidemia (38%), and smoking (34%). Relevant abnormalities were shown on cerebral angiography in 136 of 203 patients, on cardiac ultrasonography in 100 of 195, on Holter monitoring in 2 of 192; and on hypercoagulable panel in 30 of 189 patients. Multiple infarcts were observed in 31% and were more prevalent in individuals younger than age 35 years. Relevant arterial lesions were frequently detected in the middle cerebral artery (23%), internal carotid artery (13%), and vertebrobasilar arteries (13%). Cardioembolic stroke occurred in 47% (including 17% with isolated patent foramen ovale), and 11% had undetermined stroke etiology. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 0-9) and 81% had good outcome at hospital discharge. Of the 29 patients receiving thrombolysis (median National Institutes of Health Stroke Scale score, 14; interquartile range, 9-17), 55% had good outcome at hospital discharge and none developed symptomatic brain hemorrhage. This study shows the contemporary profile of ischemic stroke in young adults admitted to a tertiary stroke center. Stroke etiology can be determined in nearly 90% of patients with modern diagnostic tests. The causes are heterogeneous; however, young adults have a high rate of traditional vascular risk factors. Thrombolysis appears safe and short-term outcomes are favorable.

  19. Adherence to treatment of patients with past ischemic stroke.

    Directory of Open Access Journals (Sweden)

    V. Je. Azarenko

    2018-05-01

    Full Text Available The main task of the general practitioner is managing patients with the effects of ischemic stroke. The improvement of patients adherence to treatment in a significant way contributes to successful secondary prevention of ischemic stroke. Adherence to treatment can be determined through various questionnaires, including Morissky-Green. Currently, the adherence to a long-term drug therapy remains insufficient.

  20. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    DEFF Research Database (Denmark)

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...

  1. Diffusion-weighted MRI in acute posterior ischemic optic neuropathy

    International Nuclear Information System (INIS)

    Srinivasan, Sivasubramanian; Moorthy, Srikant; Sreekumar, KP; Kulkarni, Chinmay

    2012-01-01

    Blindness following surgery, especially cardiac surgery, has been reported sporadically, the most common cause being ischemic optic neuropathy. The role of MRI in the diagnosis of this condition is not well established. We present a case of postoperative posterior ischemic optic neuropathy that was diagnosed on diffusion-weighted MRI

  2. Effects of glycyrrhizin pre-treatment on transient ischemic brain ...

    African Journals Online (AJOL)

    Effects of glycyrrhizin pre-treatment on transient ischemic brain injury in mice. ... on transient ischemic brain injury in mice. Chiyeon Lim, Sehyun Lim, Young-Jun Lee, Bokcheul Kong, Byoungho Lee, Chang-Hyun Kim, Buyeo Kim, Suin Cho ... induced brain damage. Keywords: Glycyrrhizin, licorice, stroke, apoptosis ...

  3. Hospital costs of ischemic stroke and TIA in the Netherlands

    NARCIS (Netherlands)

    Buisman, Leander R.; Tan, Siok Swan; Nederkoorn, Paul J.; Koudstaal, Peter J.; Redekop, William K.

    2015-01-01

    Objectives:There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012.Methods:We conducted a retrospective cost analysis using individual

  4. Hospital costs of ischemic stroke and TIA in the Netherlands

    NARCIS (Netherlands)

    L.R. Buisman (Leander); S.S. Tan (Siok Swan); P.J. Nederkoorn (Paul); P.J. Koudstaal (Peter Jan); W.K. Redekop (Ken)

    2015-01-01

    markdownabstractObjectives: There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. Methods: We conducted a retrospective cost

  5. Changes of resting cerebral activities in subacute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-01-01

    Full Text Available This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients.

  6. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  7. Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3-A20 in Ischemic Stroke.

    Science.gov (United States)

    Wang, Shu-Na; Xu, Tian-Ying; Wang, Xia; Guan, Yun-Feng; Zhang, Sai-Long; Wang, Pei; Miao, Chao-Yu

    2016-09-01

    NAMPT is a novel therapeutic target of ischemic stroke. The aim of this study was to investigate the effect of a potential NAMPT activator, P7C3-A20, an aminopropyl carbazole derivative, on ischemic stroke. In vitro study, neuron protection effect of P7C3-A20 was investigated by co-incubation with primary neurons subjected to oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo experiment, P7C3-A20 was administrated in middle cerebral artery occlusion (MCAO) rats and infarct volume was examined. Lastly, the brain tissue nicotinamide adenine dinucleotide (NAD) levels were detected in P7C3-A20 treated normal or MCAO mice. Cell viability, morphology, and Tuj-1 staining confirmed the neuroprotective effect of P7C3-A20 in OGD or OGD/R model. P7C3-A20 administration significantly reduced cerebral infarction in MCAO rats. Moreover, brain NAD levels were elevated both in normal and MCAO mice after P7C3-A20 treatment. P7C3-A20 has neuroprotective effect in cerebral ischemia. The study contributes to the development of NAMPT activators against ischemic stroke and expands the horizon of the neuroprotective effect of aminopropyl carbazole chemicals. © 2016 John Wiley & Sons Ltd.

  8. Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Tang, Z; Diamond, M A; Chen, J-M; Holly, T A; Bonow, R O; Dasgupta, A; Hyslop, T; Purzycki, A; Wagner, J; McNamara, D M; Kukulski, T; Wos, S; Velazquez, E J; Ardlie, K; Feldman, A M

    2007-10-01

    The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

  9. Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

    Science.gov (United States)

    Moises, H W; Wollschläger, D; Binder, H

    2015-08-11

    In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

  10. Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

    Science.gov (United States)

    Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

    2009-11-30

    Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

  11. Feasibility of arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke

    International Nuclear Information System (INIS)

    Wang Wei; Li Cheng; Liu Zhensheng; Zhang Xinjiang; Zhou Longjiang; Yin Haiyan

    2010-01-01

    Objective: To assess the feasibility of arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke. Methods: Six patients with acute cerebral infarction within 6 hours underwent intraarterial thrombolysis, in which arterial blood bypass was used. A 2.3 F microcatheter was advanced through the clot and two milliliters of contrast was injected beyond the clot that remained stagnant in the major branches. At this point, 20 ml of oxygenated blood from femoral artery was injected for 2 minutes through the microcatheter past the occluding clot. Then, conventional intraarterial thrombolysis, including fibrinolytic agents infusion and mechanical disruption, was performed. Intraarterial thrombolysis and oxygenated blood infusion alternated every 30 minutes. Results: Every patient received arterial blood bypass with average three times (from 1 to 5 times) in the process of the intraarterial thrombolysis, which cost (8.0 ± 3.2) min. Recanalization was achieved in all 6 patients, but minor subarachnoid hemorrhage developed in one patient. All the patients got favorable clinical outcome. The life conditions is excellent in 4 cases and good in 2 cases. Conclusions: Arterial blood bypass using microcatheter in intraarterial thrombolysis for acute cerebral ischemic stroke might be feasible, which did not interfere with conventional intraarterial thrombolysis and prolong the operation time significantly but could protect ischemic penumbra. (authors)

  12. Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Robin Lemmens

    2011-01-01

    Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

  13. Ipsilateral hemiparesis in ischemic stroke patients.

    Science.gov (United States)

    Inatomi, Y; Nakajima, M; Yonehara, T; Ando, Y

    2017-07-01

    To investigate clinical characteristics of ipsilateral hemiparesis in ischemic stroke patients. Patients with acute ischemic stroke were prospectively examined. Ipsilateral hemiparesis was defined as hemiparesis ipsilateral to recent stroke lesions. Patients with ipsilateral hemiparesis were examined with functional neuroimaging studies including transcranial magnetic stimulation (TMS) and functional MRI. Of 8360 patients, ipsilateral hemiparesis was detected in 14 patients (0.17%, mean age 71±6 years, eight men). Lesions responsible for the recent strokes were located in the frontal cortex in three patients, corona radiata in seven, internal capsule in one, and pons in three. These lesions were located along the typical route of the corticospinal tract in all but one patient. Thirteen patients also had a past history of stroke contralateral to the recent lesions; 12 of these had motor deficits contralateral to past stroke lesions. During TMS, ipsilateral magnetic evoked potentials were evoked in two of seven patients and contralateral potentials were evoked in all seven. Functional MRI activated cerebral hemispheres ipsilaterally in eight of nine patients and contralaterally in all nine. Most patients with ipsilateral hemiparesis had a past history of stroke contralateral to the recent one, resulting in motor deficits contralateral to the earlier lesions. Moreover, functional neuroimaging findings indicated an active crossed corticospinal tract in all of the examined patients. Both findings suggest the contribution of the uncrossed corticospinal tract contralateral to stroke lesions as a post-stroke compensatory motor system. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Psoriasis and ischemic coronary artery disease.

    Science.gov (United States)

    Mahiques-Santos, L; Soriano-Navarro, C J; Perez-Pastor, G; Tomas-Cabedo, G; Pitarch-Bort, G; Valcuende-Cavero, F

    2015-03-01

    Psoriasis is a chronic inflammatory disease associated with an increased risk of ischemic coronary artery disease (CAD) in some populations. We aimed to determine the association between these 2 diseases in our geographic area. We performed a cross-sectional study of patient records between 2005 and 2012 in the database (Abucacis, Datamart) that contains all medical case histories in the province of Castellón, Spain. Patients diagnosed with psoriasis were compared with a control group of patients diagnosed with melanocytic nevus. The prevalence of CAD and the presence or absence of the main cardiovascular risk factors were analyzed in each group. A total of 9181 patients with psoriasis and 21925 with melanocytic nevus were studied. Univariate logistic regression analysis showed that CAD was significantly associated with psoriasis, age (in years), sex, hypertension, diabetes mellitus, dyslipidemia, and obesity (P<.05). On adjustment for age, sex, and the other cardiovascular risk factors, multivariate regression analysis established that psoriasis was independently associated with CAD (P<.029). Our findings in a large sample of patients in a Mediterranean area support the hypothesis that patients in this population have an increased risk of ischemic CAD. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  15. [Ischemic cholangiopathy induced by extended burns].

    Science.gov (United States)

    Cohen, Laurence; Angot, Emilie; Goria, Odile; Koning, Edith; François, Arnaud; Sabourin, Jean-Christophe

    2013-04-01

    Ischemic cholangiopathy is a recently described entity occurring mainly after hepatic grafts. Very few cases after intensive care unit (ICU) for extended burn injury were reported. We report the case of a 73-year-old woman consulting in an hepatology unit, for a jaundice appearing during a hospitalisation in an intensive care unit and increasing from her leaving from ICU, where she was treated for an extended burn injury. She had no pre-existing biological features of biliary disease. Biological tests were normal. Magnetic resonance imaging acquisitions of biliary tracts pointed out severe stenosing lesions of diffuse cholangiopathy concerning intrahepatic biliary tract, mainly peri-hilar. Biopsie from the liver confirmed the diagnosis, showing a biliary cirrhosis with bile infarcts. This case is the fourth case of ischemic cholangiopathy after extended burn injury, concerning a patient without a prior history of hepatic or biliary illness and appearing after hospitalisation in intensive care unit. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Hyperglycemia, Acute Ischemic Stroke and Thrombolytic Therapy

    Science.gov (United States)

    Bruno, Askiel; Fagan, Susan C.; Ergul, Adviye

    2014-01-01

    Ischemic stroke is a leading cause of disability and is considered now the 4th leading cause of death. Many clinical trials have shown that stroke patients with acute elevation in blood glucose at onset of stroke suffer worse functional outcomes, longer in-hospital stay and higher mortality rates. The only therapeutic hope for these patients is the rapid restoration of blood flow to the ischemic tissue through intravenous administration of the only currently proven effective therapy, tissue plasminogen activator (tPA). However, even this option is associated with the increased risk of intracerebral hemorrhage. Nonetheless, the underlying mechanisms through which hyperglycemia (HG) and tPA worsen the neurovascular injury after stroke are not fully understood. Accordingly, this review summarizes the latest updates and recommendations about the management of HG and co-administration of tPA in a clinical setting while focusing more on the various experimental models studying: 1. the effect of HG on stroke outcomes; 2. the potential mechanisms involved in worsening the neurovasular injury; 3. the different therapeutic strategies employed to ameliorate the injury, and finally; 4. the interaction between HG and tPA. Developing therapeutic strategies to reduce the hemorrhage risk with tPA in hyperglycemic setting is of great clinical importance. This can best be achieved by conducting robust preclinical studies evaluating the interaction between tPA and other therapeutics in order to develop potential therapeutic strategies with high translational impact. PMID:24619488

  17. Proton NMR imaging in experimental ischemic infarction

    International Nuclear Information System (INIS)

    Buonanno, F.S.; Pykett, I.L.; Brady, T.J.; Vielma, J.; Burt, C.T.; Goldman, M.R.; Hinshaw, W.S.; Pohost, G.M.; Kistler, J.P.

    1983-01-01

    Proton nuclear magnetic resonance (NMR) images depict the distribution and concentration of mobile protons modified by the relaxation times T1 and T2. Using the steady-state-free-precession (SSFP) technique, serial coronal images were obtained sequentially over time in laboratory animals with experimental ischemic infarction. Image changes were evident as early as 2 hours after carotid artery ligation, and corresponded to areas of ischemic infarction noted pathologically. Resulting SSFP images in experimental stroke are contrasted to inversion-recovery NMR images in an illustrative patient with established cerebral infarction. Bulk T1 and T2 measurements were made in vitro in three groups of gerbils: normal, those with clinical evidence of infarction, and those clinically normal after carotid ligature. Infarcted hemispheres had significantly prolonged T1 and T2 (1.47 +/- .12 sec, 76.0 +/- 9.0 msec, respectively) when compared to the contralateral hemisphere (T1 . 1.28 +/- .05 sec, T2 . 58.7 +/- 3.9 msec) or to the other two groups. These data suggest that changes in NMR parameters occur and can be detected by NMR imaging as early as two hours after carotid artery ligation

  18. Synthetic cannabis and acute ischemic stroke.

    Science.gov (United States)

    Bernson-Leung, Miya E; Leung, Lester Y; Kumar, Sandeep

    2014-01-01

    An association between marijuana use and stroke has been previously reported. However, the health risks of newer synthetic cannabinoid compounds are less well known. We describe 2 cases that introduce a previously unreported association between synthetic cannabis use and ischemic stroke in young adults. A 22-year-old woman presented with dysarthria, left hemiplegia, and left hemianesthesia within hours of first use of synthetic cannabis. She was healthy and without identified stroke risk factors other than oral contraceptive use and a patent foramen ovale without venous thromboses. A 26-year-old woman presented with nonfluent aphasia, left facial droop, and left hemianesthesia approximately 12 hours after first use of synthetic cannabis. Her other stroke risk factors included migraine with aura, oral contraceptive use, smoking, and a family history of superficial thrombophlebitis. Both women were found to have acute, large-territory infarctions of the right middle cerebral artery. Our 2 cases had risk factors for ischemic stroke but were otherwise young and healthy and the onset of their deficits occurred within hours after first-time exposure to synthetic cannabis. Synthetic cannabis use is an important consideration in the investigation of stroke in young adults. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  20. Metabolic Prosthesis for Oxygenation of Ischemic Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Greenbaum, Elias [ORNL

    2009-01-01

    This communication discloses new ideas and preliminary results on the development of a "metabolic prosthesis" for local oxygenation of ischemic tissue under physiological neutral conditions. We report for the first time the selective electrolysis of physiological saline by repetitively pulsed charge-limited electrolysis for the production of oxygen and suppression of free chlorine. For example, using 800 A amplitude current pulses and <200 sec pulse durations, we demonstrated prompt oxygen production and delayed chlorine production at the surface of a shiny 0.85 mm diameter spherical platinum electrode. The data, interpreted in terms of the ionic structure of the electric double layer, suggest a strategy for in situ production of metabolic oxygen via a new class of "smart" prosthetic implants for dealing with ischemic disease such as diabetic retinopathy. We also present data indicating that drift of the local pH of the oxygenated environment can be held constant using a feedback-controlled three electrode electrolysis system that chooses anode and cathode pair based on pH data provided by local microsensors. The work is discussed in the context of diabetic retinopathy since surgical techniques for multielectrode prosthetic implants aimed at retinal degenerative diseases have been developed.

  1. Noninvasive evaluation of ischemic stroke with SPECT

    International Nuclear Information System (INIS)

    Gomez, C.R.; Malik, M.M.; Gomez, S.M.; Wingkun, E.C.

    1988-01-01

    Technetium Tc 99m DTPA single photon emission computerized tomography (SPECT) brain scans of 20 patients with acute ischemic stroke were reviewed retrospectively and compared with clinical and radiologic (CT) data. Fourteen of the patients had abnormal SPECT studies. The abnormal findings were demonstrated by static views in eight patients, by the flow study in one patient, and by both sets of images in the other five patients. All abnormalities correlated with the clinical syndrome of presentation, and only two of the patients had no corresponding lesions on CT. Of the six patients with normal SPECT scans, two had abnormal CT studies, and in the other four, no lesions were shown at all. The ability of /sup 99m/Tc DTPA SPECT to display cerebral infarctions appears to be, at best, comparable to that of CT. SPECT also provides qualitative information regarding flow dynamics in the affected hemisphere of some patients (6/20 in our review). This, we believe, represents the objective demonstration of the preexisting insufficient collateral flow in the hemisphere at risk for ischemic stroke

  2. Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Hsiu-Fen Lin

    Full Text Available Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα. Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011, but not in men (adjusted p = 0.300.Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

  3. Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype.

    Science.gov (United States)

    Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

    2014-07-17

    TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in stroke and ischemic preconditioning and to propose, by modulating TRAIL pathway, a new therapeutic strategy in stroke. In order to achieve this aim a rat model of harmful focal ischemia, obtained by subjecting animals to 100 min of transient occlusion of middle cerebral artery followed by 24 h of reperfusion and a rat model of ischemic preconditioning in which the harmful ischemia was preceded by 30 mins of tMCAO, which represents the preconditioning protective stimulus, were used. Results show that the neuroprotection elicited by ischemic preconditioning occurs through both upregulation of TRAIL decoy receptors and downregulation of TRAIL itself and of its death receptors. As a counterproof, immunoneutralization of TRAIL in tMCAO animals resulted in significant restraint of tissue damage and in a marked functional recovery. Our data shed new light on the mechanisms that propagate ongoing neuronal damage after ischemia in the adult mammalian brain and provide new molecular targets for therapeutic intervention. Strategies aimed to repress the death-inducing ligands TRAIL, to antagonize the death receptors, or to activate the decoy receptors open new perspectives for the treatment of stroke.

  4. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  5. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    International Nuclear Information System (INIS)

    Miyanohara, Jun; Shirakawa, Hisashi; Sanpei, Kazuaki; Nakagawa, Takayuki; Kaneko, Shuji

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca"2"+ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  6. Thrombophilia testing in young patients with ischemic stroke.

    Science.gov (United States)

    Pahus, Sidse Høst; Hansen, Anette Tarp; Hvas, Anne-Mette

    2016-01-01

    The possible significance of thrombophilia in ischemic stroke remains controversial. We aimed to study inherited and acquired thrombophilias as risk factors for ischemic stroke, transient ischemic attack (TIA) and amaurosis fugax in young patients. We included patients aged 18 to 50 years with ischemic stroke, TIA or amaurosis fugax referred to thrombophilia investigation at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012 (N=685). Clinical information was obtained from the Danish Stroke Registry and medical records. Thrombophilia investigation results were obtained from the laboratory information system. Absolute thrombophilia prevalences and associated odds ratios (OR) with 95% confidence intervals (95% CI) were reported for ischemic stroke (N=377) and TIA or amaurosis fugax (N=308). Thrombophilia prevalences for the general population were obtained from published data. No strong associations were found between thrombophilia and ischemic stroke, but patients with persistent presence of lupus anticoagulant (3%) had an OR at 2.66 (95% CI 0.84-9.15) for ischemic stroke. A significantly higher risk of TIA/amaurosis fugax was found for factor V Leiden heterozygote (12%) (OR: 1.99 (95% CI 1.14-3.28)). No other inherited or acquired thrombophilia was associated with ischemic stroke, TIA or amaurosis fugax. In young patients, thrombophilia did not infer an increased risk of ischemic stroke. Only factor V Leiden heterozygote patients had an increased risk of TIA/amaurosis fugax, and persistent presence of lupus anticoagulant was likely associated with ischemic stroke. We suggest the testing restricted to investigation of persistent presence of lupus anticoagulant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Prevalence of electrocardiographic ST-T changes during acute ischemic stroke in patients without known ischemic heart disease

    DEFF Research Database (Denmark)

    Jensen, Jesper K; Bak, Søren; Flemming Høilund-Carlsen, Poul

    2008-01-01

    We evaluated characteristics and prevalence of ST-segment depression and/or T-wave inversion in the resting electrocardiogram of 244 consecutive patients with acute ischemic stroke, but without ischemic heart disease. The prevalence of ST-T changes ranged from 13% to 16% and this is what to expect...

  8. Comparison of characteristics and healing course of diabetic foot ulcers by etiological classification: neuropathic, ischemic, and neuro-ischemic type.

    Science.gov (United States)

    Yotsu, Rie Roselyne; Pham, Ngoc Minh; Oe, Makoto; Nagase, Takeshi; Sanada, Hiromi; Hara, Hisao; Fukuda, Shoji; Fujitani, Junko; Yamamoto-Honda, Ritsuko; Kajio, Hiroshi; Noda, Mitsuhiko; Tamaki, Takeshi

    2014-01-01

    To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time. Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test. The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values. Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial

    Directory of Open Access Journals (Sweden)

    Wouters Patrick

    2011-05-01

    Full Text Available Abstract Background Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC. Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF is one of the most common complications after coronary artery bypass graft surgery (CABG, affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. Methods/design This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1 control, 2 remote ischemic preconditioning, 3 remote ischemic postconditioning, or 4 remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year. Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. Discussion The RICO-trial (the effect of

  10. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  11. The research of melatonin in hypoxic-ischemic encephalopathy

    International Nuclear Information System (INIS)

    Sun Bin; Feng Xing; Qian Zhihong; Shi Ming

    2006-01-01

    Objective: To elucidate the function of melatonin in the pathogenesis and the prognosis of hypoxic-ischemic encephalopathy (HIE) and provide the pathophysiology basis for therapying HIE with melatonin. Methods: The level of plasma melatonin of twenty normal term infants and twenty modest HIE and twenty middle-severity HIE in their acute phase and recovery phase were assayed respectively with radioimmunoassay (RIA). Then compare the difference of the melatonin level among these neonates. Results: (1) For modest HIE, the melatonin level was higher than that in the normal in the acute phase and there was no difference to the normal in the recovery phase. (2) There was no difference between the melatonin level in middle-severity HIE in the acute phase and that in the normal, but in the recovery phase it was higher than that in the normal. (3) For modest HIE, the melatonin level in acute phase was higher than that in the recovery phase, but for middle-severity HIE, it was adverse. (4) In the acute phase, the level in modest HIE was higher than that in the middle-severity HIE, but on the contrary in the recovery phase. Conclusion: Melatonin have protection action on HIE. The prognosis of modest HIE neonates with rising melatonin level in the acute phase is better than that with lower melatonin level of middle-severity HIE. (authors)

  12. Premature menopause or early menopause and risk of ischemic stroke

    Science.gov (United States)

    Rocca, Walter A.; Grossardt, Brandon R.; Miller, Virginia M.; Shuster, Lynne T.; Brown, Robert D.

    2011-01-01

    Objective The general consensus has been that estrogen is invariably a risk factor for ischemic stroke (IS). We reviewed new observational studies that challenge this simple conclusion. Methods This was a review of observational studies of the association of premature or early menopause with stroke or IS published in English from 2006 through 2010. Results Three cohort studies showed an increased risk of all stroke in women who underwent bilateral oophorectomy compared with women who conserved their ovaries before age 50 years. The increased risk of stroke was reduced by hormonal therapy (HT) in one of the studies, suggesting that estrogen deprivation is involved in the association. Four additional observational studies showed an association of all stroke or IS with the early onset of menopause or with a shorter lifespan of ovarian activity. In three of the seven studies, the association was restricted to IS. Age at menopause was more important than type of menopause (natural vs induced). Conclusions The findings from seven recent observational studies challenge the consensus that estrogen is invariably a risk factor for IS and can be reconciled by a unifying timing hypothesis. We hypothesize that estrogen is protective for IS before age 50 years and may become a risk factor for IS after age 50 years or, possibly, after age 60 years. These findings are relevant to women who experienced premature or early menopause, or to women considering prophylactic bilateral oophorectomy before the onset of natural menopause. PMID:21993082

  13. PO-62 - Remote ischemic preconditioning in head and neck cancer reconstruction - a randomized controlled trial

    DEFF Research Database (Denmark)

    Krag, A E; Kiil, B J; Hvas, Christine Lodberg

    2016-01-01

    flap anastomoses or microcirculation is the main reason for total flap necrosis with potential fatal consequences for the patient. Remote ischemic preconditioning (RIPC), where brief cycles of upper extremity ischemia are induced with an inflatable tourniquet, triggers a global protection of tissues...... will be included in the trial. The subjects will be randomized to RIPC or sham during surgery. RIPC is administered by four 5-minute cycles of upper extremity ischemia, each separated by five minutes of reperfusion. Blood samples will be drawn preoperatively, before RIPC/sham, 3 hours after RIPC/ sham, 6 hours...... oncologic therapy can be initiated in timely fashion....

  14. Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

    Directory of Open Access Journals (Sweden)

    Qiu-Yan Zhang

    2017-01-01

    Full Text Available Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198, a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R, consistent results were obtained with decreased reactive oxygen species (ROS production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC- 4 which could inhibit NADPH oxidase- (NOX- 4 and matrix metalloproteinase- (MMP- 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO- 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

  15. Arctigenin attenuates ischemic stroke via SIRT1-dependent inhibition of NLRP3 inflammasome.

    Science.gov (United States)

    Zhang, Shimeng; Jiang, Liangjun; Che, Fengyuan; Lu, Yucheng; Xie, Zhongxiang; Wang, Hao

    2017-11-04

    Arctigenin (ARC), a phenylpropanoid dibenzylbutyrolactone lignan derived from Arctium lappa L, has been reported to protect against cerebral ischemia injury in rats, but the underlying mechanism is unclear. In this study, we investigated whether ARC ameliorated ischemic stroke by inhibiting NLRP3 inflammasome-derived neuroinflammation and whether SIRT1 signaling was involved in this process. ARC (20 mg/kg) or vehicle were intraperitoneally injected to Sprague-Dawley rats for 3 days before middle cerebral artery occlusion (MCAO) surgery performed. The infarct volume, neurological score, brain water content, neuroinflammation, NLRP3 inflammasome activation and SIRT1 protein expression were assessed. Furthermore, we also investigated whether ARC protected against cerebral ischemia via SIRT1-dependent inhibition of NLRP3 inflammasome by administrating EX527, a specific SIRT1 inhibitor, under oxygen-glucose deprivation (OGD) condition. We found that ARC pretreatment decreased infarct volume, neurological score and brain water content. Moreover, ARC treatment effectively inhibited cerebral ischemia induced NLRP3 inflammasome activation and IL-1β, IL-18 secretion both in vivo and in vitro. Futhermore, ARC treatment activated Silent information regulator 1 (SIRT1) singnaling in the brain. Importantly, suppress of SIRT1 reversed the inhibitory effect of ARC on NLRP3 inflammasome activation. Taken together our results demonstrated that ARC may confer protection against ischemic stroke by inhibiting NLRP3 inflammasome activation. The activation of SIRT1 signaling pathway may contribute to the neuroprotection of ARC in MCAO. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Ischemic preconditioning improves mitochondrial tolerance to experimental calcium overload.

    Science.gov (United States)

    Crestanello, Juan A; Doliba, Nicolai M; Babsky, Andriy M; Doliba, Natalia M; Niibori, Koki; Whitman, Glenn J R; Osbakken, Mary D

    2002-04-01

    Ca(2+) overload leads to mitochondrial uncoupling, decreased ATP synthesis, and myocardial dysfunction. Pharmacologically opening of mitochondrial K(ATP) channels decreases mitochondrial Ca(2+) uptake, improving mitochondrial function during Ca(2+) overload. Ischemic preconditioning (IPC), by activating mitochondrial K(ATP) channels, may attenuate mitochondrial Ca(2+) overload and improve mitochondrial function during reperfusion. The purpose of these experiments was to study the effect of IPC (1) on mitochondrial function and (2) on mitochondrial tolerance to experimental Ca(2+) overload. Rat hearts (n = 6/group) were subjected to (a) 30 min of equilibration, 25 min of ischemia, and 30 min of reperfusion (Control) or (b) two 5-min episodes of ischemic preconditioning, 25 min of ischemia, and 30 min of reperfusion (IPC). Developed pressure (DP) was measured. Heart mitochondria were isolated at end-Equilibration (end-EQ) and at end-Reperfusion (end-RP). Mitochondrial respiratory function (state 2, oxygen consumption with substrate only; state 3, oxygen consumption stimulated by ADP; state 4, oxygen consumption after cessation of ADP phosphorylation; respiratory control index (RCI, state 3/state 4); rate of oxidative phosphorylation (ADP/Deltat), and ADP:O ratio) was measured with polarography using alpha-ketoglutarate as a substrate in the presence of different Ca(2+) concentrations (0 to 5 x 10(-7) M) to simulate Ca(2+) overload. IPC improved DP at end-RP. IPC did not improve preischemic mitochondrial respiratory function or preischemic mitochondrial response to Ca(2+) loading. IPC improved state 3, ADP/Deltat, and RCI during RP. Low Ca(2+) levels (0.5 and 1 x 10(-7) M) stimulated mitochondrial function in both groups predominantly in IPC. The Control group showed evidence of mitochondrial uncoupling at lower Ca(2+) concentrations (1 x 10(-7) M). IPC preserved state 3 at high Ca(2+) concentrations. The cardioprotective effect of IPC results, in part, from

  17. METABOLIC THERAPY IN PATIENTS WITH ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    L. B. Zavaliy

    2018-01-01

    Full Text Available The article shows the world experience of metabolic therapy use in the treatment of ischemic stroke. The issue still remains prominent. The reasonability of prescribing metabolic drugs is not completely clear, its effectiveness has not been fully proved, despite numerous studies which show only trends. The article presents an overview of the most popular drugs of different pharmacological groups with a metabolic effect which affect different parts of the ischemic cascade. Ethylmethylhydroxypyridine succinate and cytoflavin have predominantly antihypoxic effect, improve functional outcome and neurological functions, and normalize overall well-being and adaptation. Cerebrolysin is a complex of low molecular weight biologically active peptides derived from the pig’s brain. It has a multimodal effect on the brain, helps to reduce the volume of cerebral infarction, restores neurologic functions and improves the functional outcome. Cortexin is a mixture of cattle brain polypeptides, also has a complex action that provides the most complete reversion of neurological deficit, improves cognitive functions and the functional outcome, reduces the level of paroxysmal convulsive readiness and improves bioelectric activity of the brain. Citicoline is a precursor of cell membrane key ultrastructures, contributes to significant reduction in the volume of cortical brain damage, improves cholinergic transmission, which results in better clinical outcome, even despite the questionable impact on the neurological status. Choline Alfoscerate is a precursor of choline, and the use of the drug significantly limits the growth of the cerebral infarction area starting from the first day of therapy, leads to reversion of neurological symptoms and achievement of rehabilitation goals. Actovegin is deproteinized derivative of calf blood, activates metabolism in tissues, improves trophism and stimulates regeneration. In a large study, it was shown that Actovegin improved

  18. Predictors of ischemic versus hemorrhagic strokes in hypertensive patients

    International Nuclear Information System (INIS)

    Khealani, B.A.; Syed, N.A.; Maken, S.; Mapari, U.U.; Hameed, B.; Ali, S.; Qureshi, R.; Akhter, N.; Hassan, A.; Sonawalla, A.B.; Baig, S.M.; Wasay, M.

    2005-01-01

    Objective: To identify the factors that predispose to ischemic versus hemorrhagic stroke in hypertensive patients. Materials and Methods: All the hypertensive patients, who were registered in AKUH acute stroke outcome data base, over a period of 22 months, were identified and from this cohort the patients with first ever stroke were selected. The data regarding demographics, stroke type (ischemic vs. hemorrhagic), pre-existing medical problems, laboratory and radiological investigations was recorded and analyzed. Results: Five hundred and nineteen patients with either ischemic stroke or parenchymal hemorrhage were registered over a period of 22 months. Three hundred and forty-eight patients (67%) had hypertension and of these, 250 had first ever stroke at the time of admission. Presence of diabetes mellitus (OR: 3.76; Cl:1.67-8.46) and ischemic heart disease (OR: 6.97; Cl:1.57-30.98) were found to be independent predictors of ischemic strokes. Conclusion: Presence of diabetes mellitus and ischemic heart disease predict ischemic stroke in a patient with hypertension. (author)

  19. Plasma Magnesium and the Risk of Ischemic Stroke among Women

    Science.gov (United States)

    Akarolo-Anthony, Sally N.; Jiménez, Monik C.; Chiuve, Stephanie E.; Spiegelman, Donna; Willett, Walter C.; Rexrode, Kathryn M.

    2014-01-01

    Background and Purpose Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. Methods Among 32,826 participants in the Nurses’ Health Study who provided blood samples in 1989–1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. Results Median magnesium levels did not differ between ischemic stroke cases and controls (median=0.86 mmol/l for both; p-value=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk (RR) of 1.34 (95% confidence interval [CI]: 0.86–2.10, p trend=0.13) for total ischemic stroke, compared to women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels magnesium levels ≥0.82 mmol/l. No significant effect modification was observed by age, body mass index, hypertension or diabetes. Conclusions Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women. PMID:25116874

  20. Correlation study on cystatin C and ischemic stroke

    Directory of Open Access Journals (Sweden)

    CHEN Rong-bo

    2013-06-01

    Full Text Available Objective To investigate the relationship between serum cystatin C (Cys C and patients with acute ischemic stroke. Methods The clinical and laboratory data of 115 patients with acute ischemic stroke and 110 controls were recorded and analyzed. Results The serum Cys C levels of patients in ischemic stroke group [(1.15 ± 0.34 mg/L] were higher than that of the control group [(0.99 ± 0.25 mg/L]. The difference between two groups was significant after correction of age and cardiovascular risk factors (t = ? 3.889, P = 0.000. It was found that age, Cys C, homocysteine (Hcy, type 2 diabetes mellitus [hemoglobin A1c (HbA1c, fructosamine (FRU], smoking, alcohol consumption, hypertension and intima-media thickness (IMT were risk factors for ischemic stroke on univariate Logistic regression analysis. The difference of serum Cys C level between the patients and controls was significant (P = 0.000, but through covariance analysis, after adjusted other risk factors, it was not significant (P = 0.875. Conclusion The serum Cys C levels of patients in ischemic stroke group is higher than the control group. It can be used as an indicator in the acute phase of ischemic stroke. The elevation of serum Cys C is a risk factor for ischemic stroke, but not an independent risk factor.

  1. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  2. Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke.

    Science.gov (United States)

    Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena

    2017-01-01

    Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone is also synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain. Apart from performing crucial reproductive functions, it also plays a pivotal role in neurogenesis, regeneration, cognition, mood, inflammation, and myelination in the CNS. A substantial body of experimental evidence from animal models documents the neuroprotective role of P4 in various CNS injury models, including ischemic stroke. Extensive data have revealed that P4 elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies. Data regarding the neuroprotective role of P4 in ischemic stroke are of great interest due to their potential clinical implications. In this review, we succinctly discuss the biosynthesis of P4 and distribution of P4 receptors (PRs) in the brain. We summarize our work on the general mechanisms of P4 mediated via the modulation of different PR and neurotransmitters. Finally, we describe the neuroprotective mechanisms of P4 in ischemic stroke models and related clinical prospects.

  3. Post-ischemic bowel stricture: CT features in eight cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Sil [Dept. of Radiology, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul (Korea, Republic of); Kim, Hyun Jin; Hong, Sung Mo; Park, Seong Ho; Lee, Jong Seok; Kim, Ah Young; Ha, Hyun Kwon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To investigate the characteristic radiologic features of post-ischemic stricture, which can then be implemented to differentiate that specific disease from other similar bowel diseases, with an emphasis on computed tomography (CT) features. Eight patients with a diagnosis of ischemic bowel disease, who were also diagnosed with post-ischemic stricture on the basis of clinical or pathologic findings, were included. Detailed clinical data was collected from the available electronic medical records. Two radiologists retrospectively reviewed all CT images. Pathologic findings were also analyzed. The mean interval between the diagnosis of ischemic bowel disease and stricture formation was 57 days. The severity of ischemic bowel disease was variable. Most post-ischemic strictures developed in the ileum (n = 5), followed by the colon (n = 2) and then the jejunum (n = 1). All colonic strictures developed in the “watershed zone.” The pathologic features of post-ischemic stricture were deep ulceration, submucosal/subserosal fibrosis and chronic transmural inflammation. The mean length of the post-ischemic stricture was 7.4 cm. All patients in this study possessed one single stricture. On contrast-enhanced CT, most strictures possessed concentric wall thickening (87.5%), with moderate enhancement (87.5%), mucosal enhancement (50%), or higher enhancement in portal phase than arterial phase (66.7%). Post-ischemic strictures develop in the ileum, jejunum and colon after an interval of several weeks. In the colonic segment, strictures mainly occur in the “watershed zone.” Typical CT findings include a single area of concentric wall thickening of medium length (mean, 7.4 cm), with moderate and higher enhancement in portal phase and vasa recta prominence.

  4. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  5. Critical care management of acute ischemic stroke.

    Science.gov (United States)

    Coplin, William M

    2012-06-01

    Acute ischemic stroke (AIS) can have profound and devastating effects on the CNS and several other organs. Approximately 15% to 20% of patients with AIS are admitted to an intensive care unit and cared for by a multidisciplinary team. This article discusses the critical care management of patients with AIS. Patients with AIS require attention to airway, pulmonary status, blood pressure, glucose, temperature, cardiac function, and, sometimes, life-threatening cerebral edema. The lack of disease-specific data has led to numerous management approaches and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of bleeding but provide little discussion of the complex critical care issues involved in caring for patients with AIS.

  6. Use of nitrates in ischemic heart disease.

    Science.gov (United States)

    Giuseppe, Cocco; Paul, Jerie; Hans-Ulrich, Iselin

    2015-01-01

    Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the incidence of acute coronary syndromes, while data from another multivariate study indicate that they have positive effects. Because of methodological differences and open questions, the two studies cannot be compared. A study in Japanese patients with vasospastic angina has shown that, when compared with calcium antagonists, long-acting nitrates do not improve long-term prognosis and that the risk for cardiac adverse events increases with the combined therapy. We have many unanswered questions.

  7. Citicoline for ischemic stroke: ICTUS trial

    Directory of Open Access Journals (Sweden)

    Vladimir Anatolyevich Parfenov

    2012-01-01

    Full Text Available The paper gives data available in the literature on the use of citicoline in an experimental model of ischemic stroke (IS and in randomized multicenter placebo-controlled trials. It analyzes the results of the ICTUS trial in which 2298 patients with IS who received randomly citicoline or placebo for 24 hours after the onset of symptoms (I000 mg intravenously every I2 hours during the first 3 days, then orally as one 500-mg tablet every 12 hours during 6 weeks. The results of the trial confirmed the safety of citicoline used in IS, but failed to show its significant advantage over placebo in reducing the degree of disability (global improvement 90 days later. However, to pool the results of the ICTUS trial with those of other randomized multicenter placebo-controlled studies demonstrates a significant decrease in the degree of disability in IS patients treated with citicoline.

  8. Metabolically Healthy Obesity and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Hansen, Louise; Netterstrom, Marie K.; Johansen, Nanna B.

    2017-01-01

    Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart...... risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome...... Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less...

  9. Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

    Science.gov (United States)

    Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

    2014-01-01

    Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

  10. [Secondary prevention of ischemic non cardioembolic stroke].

    Science.gov (United States)

    Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere

    2015-01-01

    Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  11. Acute ischemic stroke. Imaging and intervention

    International Nuclear Information System (INIS)

    Gonzalez, R.G.; Lev, M.H.; Hirsch, J.A.; Koroshetz, W.J.; Schaefer, P.

    2006-01-01

    This timely book provides basic, practical and up-to-date information on how to use imaging to diagnose and treat patients with acute ischemic stroke. Written by physicians from the Massachusetts General Hospital and faculty from the Harvard Medical School, the book distills years of experience in the day-to-day management of acute stroke patients, as well as leading-edge basic and clinical research, into a practical guide. With the growing awareness that modern CT and MR imaging can meaningfully improve the outcome of the acute stroke patient, this book provides the practical information to advance the capacities of providers in delivering the most advanced care for this disease. (orig.)

  12. Clinical evaluation of ischemic heart diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Fumio [Sendai Railway Hospital (Japan)

    1983-09-01

    Attempt were made to detect the existence of myocardial ischemia by means of both radiographic and scintigraphic techniques. Firstly, a new polygraph was especially designed for selecting the arbitrary phases in a cardiac cycle at which the corresponding radiogram should be synchronously obtained. A comparative investigation on the difference between end-systolic and-diastolic cardiac transverse diameters revealed a remarkable difference of 3.6% in normal subjects and 0.6% in patients with ischemic heart disease. These data indicating the difference of overall heart size was reflected in local dyskinesis documentation of recently developed techniques. For daily clinical purposes, radiography of the chest based on synchronously selected phases would contribute to accurate diagnosis and treatment of heart disease. Secondly, scintigraphic display using intravenously injected thallium-201 was clinically applied. For detection of ischemia, comparative study was performed of initial image relative to selective coronary cineangiography and stress scintigraphy. The former indicated a good correlation of 90%, whereas the latter served to enhance sensitivity. Sequential images (initial and delayed) facilitated the distinction of normal, necrotic, and ischemic areas. Scintigram was used for objective evaluation of coronary dilator (dilazep), either at immediate or follow-up stage. In the same way, it was also possible to indicate the effectiveness of sublingually given nitroglycerin by myocardial scintigram, where by significant increase of uptake was observed 20 minutes after administration. Rehabilitation after acute heart disease was discussed, especially on the peripheral effect. Ratio of the thigh muscle to myocardium shown in this study was useful for objective evaluation. Another preliminary study is to separate normal coronary arteries from myocardial necrosis.

  13. Clinical evaluation of ischemic heart diagnosis

    International Nuclear Information System (INIS)

    Kamei, Fumio

    1983-01-01

    Attempt were made to detect the existence of myocardial ischemia by means of both radiographic and scintigraphic techniques. Firstly, a new polygraph was especially designed for selecting the arbitrary phases in a cardiac cycle at which the corresponding radiogram should be synchronously obtained. A comparative investigation on the difference between end-systolic and-diastolic cardiac transverse diameters revealed a remarkable difference of 3.6% in normal subjects and 0.6% in patients with ischemic heart disease. These data indicating the difference of overall heart size was reflected in local dyskinesis documentation of recently developed techniques. For daily clinical purposes, radiography of the chest based on synchronously selected phases would contribute to accurate diagnosis and treatment of heart disease. Secondly, scintigraphic display using intravenously injected thallium-201 was clinically applied. For detection of ischemia, comparative study was performed of initial image relative to selective coronary cineangiography and stress scintigraphy. The former indicated a good correlation of 90%, whereas the latter served to enhnace sensitivity. Sequential images (initial and delayed) facilitated the distinction of normal, necrotic, and ischemic areas. Scintigram was used for objective evaluation of coronary dilator (dilazep), either at immediate or follow-up stage. In the same way, it was also possible to indicate the effectiveness of sublingually given nitroglycerin by myocardial scintigram, where by significant increase of uptake was observed 20 minutes after administration. Rehabilitation after acute heart disease was discussed, especially on the peripheral effect. Ratio of the thigh muscle to myocardium shown in this study was useful fer objective evaluation. Another preliminary study is to separate normal coronary arteries from myocardial necrosis. (J.P.N.)

  14. Severe ischemic colitis following olanzapine use: a Case Report

    Directory of Open Access Journals (Sweden)

    Samuel Raimundo Fernandes

    Full Text Available Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

  15. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  16. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2015-12-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  17. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  18. The peptide NDP-MSH induces phenotype changes in the heart that resemble ischemic preconditioning.

    Science.gov (United States)

    Catania, Anna; Lonati, Caterina; Sordi, Andrea; Leonardi, Patrizia; Carlin, Andrea; Gatti, Stefano

    2010-01-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) is a pro-opiomelanocortin (POMC)-derived peptide that exerts multiple protective effects on host cells. Previous investigations showed that treatment with alpha-MSH or synthetic melanocortin agonists reduces heart damage in reperfusion injury and transplantation. The aim of this preclinical research was to determine whether melanocortin treatment induces preconditioning-like cardioprotection. In particular, the plan was to assess whether melanocortin administration causes phenotype changes similar to those induced by repetitive ischemic events. The idea was conceived because both ischemic preconditioning and melanocortin signaling largely depend on cAMP response element binding protein (CREB) phosphorylation. Rats received single i.v. injections of 750microg/kg of the alpha-MSH analogue Nle(4),DPhe(7)-alpha-MSH (NDP-MSH) or saline and were sacrificed at 0.5, 1, 3, or 5h. Western blot analysis showed that rat hearts expressed melanocortin 1 receptor (MC1R) protein. Treatment with NDP-MSH was associated with early and marked increase in interleukin 6 (IL-6) mRNA. This was followed by signal transducer and activator of transcription 3 (STAT3) phosphorylation and induction of suppressor of cytokine signaling 3 (SOCS3). There were no changes in expression of other cytokines of the IL-6 family. Expression of IL-10, IL-1beta, and TNF-alpha was likewise unaltered. In hearts of rats treated with NDP-MSH there was increased expression of the orphan nuclear receptor Nur77. The data indicate that NDP-MSH induces phenotype changes that closely resemble ischemic preconditioning and likely contribute to its established protection against reperfusion injury. In addition, the increased expression of Nur77 and SOCS3 could be part of a broader anti-inflammatory effect.

  19. RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

    Science.gov (United States)

    Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

    2015-01-01

    Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

  20. Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Brulhart-Meynet

    Full Text Available New evidence shows that high density lipoproteins (HDL have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI. However, basic rHDL composition is limited to apolipoprotein AI (apoAI and phospholipids; addition of bioactive compound may enhance its beneficial effects.The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P in rHDL formulations.The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff model and the in vivo model (-48%, p<0.01. Treatment with rHDL of basic formulation (apoAI + phospholipids had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01. This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes and in vivo.HDL afford protection against IRI in a clinically relevant model (post-ischemia. rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

  1. Prothrombin and risk of venous thromboembolism, ischemic heart disease and ischemic cerebrovascular disease in the general population

    DEFF Research Database (Denmark)

    Weischer, Maren; Juul, Klaus; Zacho, Jeppe

    2010-01-01

    OBJECTIVE: We tested the hypotheses that Prothrombin G20210A heterozygosity associate with increased risk of venous thromboembolism (VTE), ischemic heart disease (IHD), and ischemic cerebrovascular disease (ICVD) in the general population and re-tested risk of IHD and ICVD in two case......-control studies. METHODS: 9231 individuals from the Danish general population were followed for VTE (VTE=DVT+PE), deep venous thrombosis (DVT), pulmonary embolism (PE), IHD, myocardial infarction (MI), ICVD, and ischemic stroke (IS) for a median of 24 years. Case-control studies included 2461 IHD cases and 867...

  2. Protective effect of atorvastatin on radiation-induced vascular endothelial cell injury in vitro

    International Nuclear Information System (INIS)

    Ran Xinze; Zong Zhaowen; Liu Dengqun; Su Yongping; Zheng Huaien; Ran Xi; Xiang Guiming

    2010-01-01

    Vascular endothelial cells are very sensitive to ionizing radiation, and it is important to develop effective prevent agents and measures in radiation exposure protection. In the present study, the protective effects of atorvastatin on irradiated human umbilical vein endothelial cells (HUVEC) and the possible mechanisms were explored. Cultured HUVEC were treated by atorvastatin at a final concentration of 10 μmol/ml for 10 minutes, and then irradiated at a dose of 2 Gy or 25 Gy. Twenty-four hours after irradiation, apoptosis of HUVEC was monitored by flow cytometry, and the expression of thrombomodulin (TM) and protein C activation in HUVEC was respectively assessed by flow cytometry and spectrophotometry. After treatment with atorvastatin for 24 h, the rate of cell apoptosis decreased by 6% and 16% in cells irradiated with 2 Gy and 25 Gy, respectively. TM expression increased by 77%, 59%, and 61% in untreated cells, 2 Gy irradiation-treated cells, and 25 Gy irradiation-treated cells, respectively. The protein C levels in 2 Gy and 25 Gy irradiation-treated cells were reduced by 23% and 34% when compared with untreated cells, but up-regulated by 79% and 76% when compared with cells which were irradiated and treated with atorvastatin. In conclusion, these data indicate that atorvastatin exerts protective effects on irradiated HUVEC by reducing apoptosis by up-regulating TM expression and enhancing protein C activation in irradiated HUVEC. (author)

  3. Protective effect of atorvastatin on radiation-induced vascular endothelial cell injury in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xinze, Ran; Zhaowen, Zong; Dengqun, Liu; Yongping, Su; Huaien, Zheng [College of Preventive Medicine, Third Military Medical Univ., Chongqing (China); Xi, Ran; Guiming, Xiang [Xinqiao Hospital, Third Military Medical Univ., Chongqing (China)

    2010-09-15

    Vascular endothelial cells are very sensitive to ionizing radiation, and it is important to develop effective prevent agents and measures in radiation exposure protection. In the present study, the protective effects of atorvastatin on irradiated human umbilical vein endothelial cells (HUVEC) and the possible mechanisms were explored. Cultured HUVEC were treated by atorvastatin at a final concentration of 10 {mu}mol/ml for 10 minutes, and then irradiated at a dose of 2 Gy or 25 Gy. Twenty-four hours after irradiation, apoptosis of HUVEC was monitored by flow cytometry, and the expression of thrombomodulin (TM) and protein C activation in HUVEC was respectively assessed by flow cytometry and spectrophotometry. After treatment with atorvastatin for 24 h, the rate of cell apoptosis decreased by 6% and 16% in cells irradiated with 2 Gy and 25 Gy, respectively. TM expression increased by 77%, 59%, and 61% in untreated cells, 2 Gy irradiation-treated cells, and 25 Gy irradiation-treated cells, respectively. The protein C levels in 2 Gy and 25 Gy irradiation-treated cells were reduced by 23% and 34% when compared with untreated cells, but up-regulated by 79% and 76% when compared with cells which were irradiated and treated with atorvastatin. In conclusion, these data indicate that atorvastatin exerts protective effects on irradiated HUVEC by reducing apoptosis by up-regulating TM expression and enhancing protein C activation in irradiated HUVEC. (author)

  4. Safety and feasibility of post-stroke care and exercise after minor ischemic stroke or transient ischemic attack: MotiveS & MoveIT

    NARCIS (Netherlands)

    Boss, H.M.; Van Schaik, S.M.; Deijle, I.A.; de Melker, E.C.; van den Berg, B.M.; Scherder, E.J.A.; Bosboom, W.M.J.; Weinstein, H.C.; van den Berg-Vos, R.M.

    2014-01-01

    Background: Despite the beneficial effect of cardiac rehabilitation after myocardial infarction, a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack (TIA). Objective: To

  5. [Preditive clinical factors for epileptic seizures after ischemic stroke].

    Science.gov (United States)

    Fukujima, M M; Cardeal, J O; Lima, J G

    1996-06-01

    Preditive clinical factors for epileptic seizures after ischemic stroke. Clinical features of 35 patients with ischemic stroke who developed epilepsy (Group 1) were compared with those of 35 patients with ischemic stroke without epilepsy (Group 2). The age of the patients did not differ between the groups. There were more men than women and more white than other races in both groups. Diabetes melitus, hypertension, transient ischemic attack, previous stroke, migraine, Chagas disease, cerebral embolism of cardiac origin and use of oral contraceptive did not differ between the groups. Smokers and alcohol users were more frequent in Group 1 (p < 0.05). Most patients of Group 1 presented with hemiparesis; none presented cerebellar or brainstem involvement. Perhaps strokes in smokers have some different aspects, that let them more epileptogenic than in non smokers.

  6. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management

    NARCIS (Netherlands)

    Kruyt, Nyika D.; Biessels, Geert Jan; DeVries, J. Hans; Roos, Yvo B.

    2010-01-01

    Patients with acute ischemic stroke frequently test positive for hyperglycemia, which is associated with a poor clinical outcome. This association between poor glycemic control and an unfavorable prognosis is particularly evident in patients with persistent hyperglycemia, patients without a known

  7. Anterior ischemic optic neuropathy in patients undergoing hemodialysis

    NARCIS (Netherlands)

    DoorenbosBot, ACC; Geerlings, W; Houtman, IA

    Four patients are discussed who underwent hemodialysis and developed anterior ischemic optic neuropathy (AION). Three patients had been treated by hemodialysis for several years. One patient developed bilateral optic neuropathy after the first hemodialysis session, So far, only four hemodialysis

  8. The Migraine-Ischemic Stroke Relation in Young Adults

    Directory of Open Access Journals (Sweden)

    Alessandro Pezzini

    2011-01-01

    Full Text Available In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1 the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2 migraine is associated with an increased prevalence of cardiovascular risk factors; (3 the link is caused by migraine-specific drugs; (4 migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.

  9. The Migraine-Ischemic Stroke Relation in Young Adults

    Science.gov (United States)

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2011-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

  10. Sexual dimorphism in ischemic stroke: lessons from the laboratory

    Science.gov (United States)

    Manwani, Bharti; McCullough, Louise D

    2011-01-01

    Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms. PMID:21612353

  11. Extracranial cerebral arterial atherosclerosis in Iranian patients suffering ischemic strokes

    Directory of Open Access Journals (Sweden)

    Sayed Ali Mousavi

    2006-12-01

    Full Text Available BACKGROUND: To determine the distribution and severity of extracranial carotid arterial atherosclerosis in Iranian patients with ischemic stroke. METHODS: 328 patients with ischemic stroke were included in this study. Doppler ultrasound was used for evaluation of atherosclerosis in extracranial carotid arteries. The NASCET criteria were used to measure carotid stenosis. RESULTS: Ninety of 328 patients (27.4% were found to have atherosclerotic plaques; 40 of these patients were women and 50 were men. Sixty-eight patients (20.7% had artery stenosis <50%, 13 patients (3.95% had 50-70 % artery stenosis and 6 (1.8% had >70% artery stenosis. CONCLUSIONS: Extracranial atherosclerosis is not rare in Iranian patients with ischemic stroke, but most carotid artery lesions were plaques with <50% stenosis. KEY WORDS: Atherosclerosis, ischemic stroke, carotid stenosis.

  12. Prognostic Factors and Outcome of Management of Ischemic ...

    African Journals Online (AJOL)

    management, prognostic factors, and outcome of ischemic priapism in patients seen at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. ..... Financial support and sponsorship. Nil. ... European Association of Urology guidelines on.

  13. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Jensen, J S; Feldt-Rasmussen, B; Strandgaard, S

    2000-01-01

    Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among...... hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease......, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person...

  14. Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke

    DEFF Research Database (Denmark)

    Andersen, Søren Due; Skjøth, Flemming; Yavarian, Yousef

    2016-01-01

    ackground: Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events...... in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). Methods: We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes...... as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we...

  15. Advances in endovascular therapy for ischemic cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Jun Lu

    2016-09-01

    Full Text Available Endovascular therapy for ischemic cerebrovascular diseases has developed rapidly in recent years. The latest clinical trials of acute ischemic stroke have shown promising results with the continued advancement of concepts, techniques, and materials. Mechanical thrombectomy is recommended in the treatment of acute ischemic stroke caused by large vessel occlusion of the anterior circulation, according to the guidelines updated in Europe, USA, and China. The long-term therapeutic efficacy of endovascular stenting for carotid artery stenosis has also been proved noninferior to that of carotid endarterectomy. However, the latest clinical trials have shown that the efficacy of stenting for intracranial artery and vertebral artery stenosis is inferior to that of medical treatment alone, which needs urgent attention through further development and studies. Keywords: Ischemic cerebrovascular diseases, Interventional surgery, Progress

  16. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  17. Evaluation of the Effects of Atorvastatin and Ischemic Postconditioning Preventing on the Ischemia and Reperfusion Injury: Experimental Study in Rats

    Directory of Open Access Journals (Sweden)

    Henrique Budib Dorsa Pontes

    Full Text Available Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus were distributed in 5 groups: Ischemia and Reperfusion (A, Ischemic Postconditioning (B, Statin (C, Ischemic Postconditioning + Statins (D and SHAM (E. After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029. The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001. The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001. The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006. The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.

  18. Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines.

    Science.gov (United States)

    Chao de la Barca, Juan Manuel; Bakhta, Oussama; Kalakech, Hussein; Simard, Gilles; Tamareille, Sophie; Catros, Véronique; Callebert, Jacques; Gadras, Cédric; Tessier, Lydie; Reynier, Pascal; Prunier, Fabrice; Mirebeau-Prunier, Delphine

    2016-09-24

    Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role. Rat plasma samples from RIPC and control groups were analyzed using a targeted metabolomic approach aimed at measuring 188 metabolites. Principal component analysis and orthogonal partial least-squares discriminant analysis were used to identify the metabolites that discriminated between groups. Plasma samples from 50 patients subjected to RIPC were secondarily explored to confirm the results obtained in rats. Finally, a combination of the metabolites that were significantly increased in both rat and human plasma was injected prior to myocardial ischemia/reperfusion in rats. In the rat samples, 124 molecules were accurately quantified. Six metabolites (ornithine, glycine, kynurenine, spermine, carnosine, and serotonin) were the most significant variables for marked differentiation between the RIPC and control groups. In human plasma, analysis confirmed ornithine decrease and kynurenine and glycine increase following RIPC. Injection of the glycine and kynurenine alone or in combination replicated the protective effects of RIPC seen in rats. We have hereby reported significant variations in a cocktail of amino acids and biogenic amines after remote ischemic preconditioning in both rat and human plasma. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01390129. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Neuroprotection by curcumin in ischemic brain injury involves the Akt/Nrf2 pathway.

    Directory of Open Access Journals (Sweden)

    Jingxian Wu

    Full Text Available Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(PH: quinone oxidoreductase1 (NQO1 induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2 to antioxidant response element (ARE were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage.

  20. Neuroprotection by Curcumin in Ischemic Brain Injury Involves the Akt/Nrf2 Pathway

    Science.gov (United States)

    Wu, Jingxian; Li, Qiong; Wang, Xiaoyan; Yu, Shanshan; Li, Lan; Wu, Xuemei; Chen, Yanlin; Zhao, Jing; Zhao, Yong

    2013-01-01

    Oxidative damage plays a critical role in many diseases of the central nervous system. This study was conducted to determine the molecular mechanisms involved in the putative anti-oxidative effects of curcumin against experimental stroke. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular expression of NAD(P)H: quinone oxidoreductase1 (NQO1) induced by OGD was counteracted by curcumin post-treatment, which paralleled attenuated cell injury. The reduction of phosphorylation Akt induced by OGD was restored by curcumin. Consequently, NQO1 expression and the binding activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) to antioxidant response element (ARE) were increased. LY294002 blocked the increase in phospho-Akt evoked by curcumin and abolished the associated protective effect. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 60 minutes. Curcumin administration significantly reduced infarct size. Curcumin also markedly reduced oxidative stress levels in middle cerebral artery occlusion (MCAO) rats; hence, these effects were all suppressed by LY294002. Taken together, these findings provide evidence that curcumin protects neurons against ischemic injury, and this neuroprotective effect involves the Akt/Nrf2 pathway. In addition, Nrf2 is involved in the neuroprotective effects of curcumin against oxidative damage. PMID:23555802

  1. Cyclical blood flow restriction resistance exercise: a potential parallel to remote ischemic preconditioning?

    Science.gov (United States)

    Sprick, Justin D; Rickards, Caroline A

    2017-11-01

    Remote ischemic preconditioning (RIPC) is characterized by the cyclical application of limb blood flow restriction and reperfusion and has been shown to protect vital organs during a subsequent ischemic insult. Blood flow restriction exercise (BFRE) similarly combines bouts of blood flow restriction with low-intensity exercise and thus could potentially emulate the protection demonstrated by RIPC. One concern with BFRE, however, is the potential for an augmented rise in sympathetic outflow due to greater activation of the exercise pressor reflex. Because of the use of lower workloads, however, we hypothesized that BFRE would elicit an attenuated increase in sympathetic outflow [assessed via plasma norepinephrine (NE) and mean arterial pressure (MAP)] and middle cerebral artery velocity (MCAv) when compared with conventional exercise (CE). Fifteen subjects underwent two leg press exercise interventions: 1 ) BFRE-220 mmHg bilateral thigh occlusion at 20% 1 rep-max (1RM), and 2 ) CE-65% 1RM without occlusion. Each condition consisted of 4 × 5-min cycles of exercise, with 3 × 10-reps in each cycle. Five minutes of rest and reperfusion (for BFRE) followed each cycle. MAP increased with exercise ( P exercise ( P exercise only ( P = 0.07). Plasma NE concentration increased with CE only ( P exercise ( P ≤ 0.02). The attenuated sympathetic response, combined with similar cerebrovascular responses, suggest that cyclical BFRE could be explored as an alternative to CE in the clinical setting. Copyright © 2017 the American Physiological Society.

  2. Association between seizures after ischemic stroke and stroke outcome

    OpenAIRE

    Xu, Tao; Ou, Shu; Liu, Xi; Yu, Xinyuan; Yuan, Jinxian; Huang, Hao; Chen, Yangmei

    2016-01-01

    Abstract A systematic review and meta-analysis were performed to investigate a potential association between post-ischemic stroke seizures (PISS) and subsequent ischemic stroke (IS) outcome. A systematic search of two electronic databases (Medline and Embase) was conducted to identify studies that explored an association between PISS and IS outcome. The primary and secondary IS outcomes of interest were mortality and disability, respectively, with the latter defined as a score of 3 to 5 on th...

  3. Hospital costs of ischemic stroke and TIA in the Netherlands.

    Science.gov (United States)

    Buisman, Leander R; Tan, Siok Swan; Nederkoorn, Paul J; Koudstaal, Peter J; Redekop, William K

    2015-06-02

    There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. We conducted a retrospective cost analysis using individual patient data from a national diagnosis-related group registry. We analyzed 4 subgroups: inpatient ischemic stroke, inpatient TIA, outpatient ischemic stroke, and outpatient TIA. Costs of carotid endarterectomy and costs of an extra follow-up visit were also estimated. Unit costs were based on reference prices from the Dutch Healthcare Insurance Board and tariffs provided by the Dutch Healthcare Authority. Linear regression analysis was used to examine the association between hospital costs and various patient and hospital characteristics. A total of 35,903 ischemic stroke and 21,653 TIA patients were included. Inpatient costs were €5,328 ($6,845) for ischemic stroke and €2,470 ($3,173) for TIA. Outpatient costs were €495 ($636) for ischemic stroke and €587 ($754) for TIA. Costs of carotid endarterectomy were €6,836 ($8,783). Costs of inpatient days were the largest contributor to hospital costs. Age, hospital type, and region were strongly associated with hospital costs. Hospital costs are higher for inpatients and ischemic strokes compared with outpatients and TIAs, with length of stay (LOS) the most important contributor. LOS and hospital costs have substantially declined over the last 10 years, possibly due to improved hospital stroke care and efficient integrated stroke services. © 2015 American Academy of Neurology.

  4. Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management.

    Science.gov (United States)

    Berry, Shauna; Lin, Weijie V; Sadaka, Ama; Lee, Andrew G

    2017-01-01

    Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea). The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION.

  5. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    International Nuclear Information System (INIS)

    Kannan, Anusha; Srinivasan, Sivasubramanian

    2012-01-01

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  6. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

    2012-09-15

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  7. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  8. The Migraine-Ischemic Stroke Relation in Young Adults

    OpenAIRE

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2010-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by s...

  9. Health behavior of patients with ischemic heart disease

    OpenAIRE

    Paweł Węgorowski; Joanna Michalik; Rafał Zarzeczny; Renata Domżał-Drzewiecka; Grzegorz Nowicki

    2017-01-01

    Admission By analyzing the available scientific literature, it is possible to define ischemic heart disease as a set of disease symptoms that are a consequence of a chronic state of imbalance between the ability to supply nutrients and oxygen and the real need of myocardial cells for these substances. Adapting life-style behaviors to healthy living is a priority to prevent the onset and development of cardiovascular disease, especially ischemic heart disease, Purpose of research T...

  10. Smoking and Risk of Ischemic Stroke in Young Men.

    Science.gov (United States)

    Markidan, Janina; Cole, John W; Cronin, Carolyn A; Merino, Jose G; Phipps, Michael S; Wozniak, Marcella A; Kittner, Steven J

    2018-05-01

    There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ 2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men. © 2018 American Heart Association, Inc.

  11. Basic and clinical research advances in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Yuan-yuan MA

    2018-01-01

    Full Text Available Stroke is the most common cerebrovascular disease worldwide, which seriously affects life quality of survivals and results in huge economic burden of families and society. In terms of clinical treatment for ischemic stroke, apart from thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA, the occurrence and successful application of endovascular thrombectomy in patients of ischemic stroke is a major breakthrough. Meanwhile, many novel clinical drugs for ischemic stroke therapy have entered into clinical trials. Most of basic and clinical researches have showed promising results in ischemic stroke therapy. This review mainly summarizes the progress of research during the period of Twelfth Five-Year Plan for National Economic and Social Development on treatment of ischemic stroke, including omics technologies, gene therapy, microRNA (miRNA interference and stem cell therapy. Stem cell therapy has shown great potential since many clinical trials have been completed or are ongoing. The development and mutual transformation of basic and clinical research will provide valuable and comprehensive information for the precise treatment of ischemic stroke.

  12. Transient Ischemic Attack Caused by Iron Deficiency Anemia

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    Ufuk Emre

    2006-02-01

    Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

  13. Hepatitis isquémica Ischemic hepatitis

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    Marcos Amuchástegui (h

    2006-10-01

    Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

  14. Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

    Science.gov (United States)

    Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

    2011-12-31

    An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

  15. Effectiveness of home rehabilitation for ischemic stroke

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    Pakaratee Chaiyawat

    2009-08-01

    Full Text Available The objective of this study was to develop and examine the effectiveness of an individual home rehabilitation program for patients with ischemic stroke. This was a randomized controlled trial in 60 patients with recent middle cerebral artery infarction. After hospital discharge for acute stroke care, they were randomly assigned to receive either a home rehabilitation program for three months (intervention group or usual care (control group. We collected outcome data over three months after their discharge from the hospital. The Barthel Index (BI, the Modified Rankin Scale (MRS, the health-related quality-of-life index (EQ-5D, the Hospital Anxiety and Depression score (HADs, and the Thai Mental State Examination (TMSE were used to analyze the outcomes. In the intervention group, all outcomes were significantly better (p<0.05 than in the control group, except in the case of TMSE. A favorable outcome, which was defined as minimal or no disability as measured by BI (score 95-100, was achieved by 93.33% of patients in the intervention group, and 90% had favorable scores (0 or 1 on the MRS. This showed a benefit in reducing disability, with two being the number of patients considered as needed-to-treat (NNT (95% CI, 1.0-1.2. All dimensions of EQ-5D in the intervention group were significantly better for quality of life and generic health status than in the control group (p=0.001. Depression was found in one patient (3.33% in the intervention group and in two patients (6.67% in the control group. Dementia was found in three patients (10% in the intervention group and in four patients (13.33% in the control group. We concluded that an early home rehabilitation program for patients with ischemic stroke in the first three-month period provides significantly better outcomes in improving function, reducing disability, increasing quality of life, and reducing depression than a program of usual care does.

  16. 31P nuclear magnetic resonance surface coil study of ischemic preconditioned isolated perfused rat heart

    International Nuclear Information System (INIS)

    Yan Yongbin; Luo Xuechun; Zhang Riqing; Wang Xiaoyin; Zuo Lin; Liu Wei

    2000-01-01

    ischemic preconditioning (IPC) will protect the heart from the damage caused by a subsequent long ischemia period. 31 P spectra of isolated perfused rat heart measured by the nuclear magnetic resonance (NMR) surface coil technique can be used to continually, dynamically and noninvasively obtain metabolism information. This paper explores the IPC mechanisms by NMR. This study shows that IPC has no effect on enhancing the ATP and PCr levels during reperfusion but makes significantly slows and smooths the changes of intracellular pH and ATP during ischemia periods. The ATP and PCr recovery rate of the IPC group after ischemia is significantly higher than that of the control group. In conclusion, the above results support that IPC can protect the rat heart by reducing damage during the ischemia period

  17. Classification of etiologic subtypes for transient ischemic attacks. Clinical significance of lacunar transient ischemic attack

    International Nuclear Information System (INIS)

    Ohara, Tomoyuki; Yamamoto, Yasumasa; Nagakane, Yoshinari; Tanaka, Eijiro; Morii, Fukiko; Koizumi, Takashi

    2011-01-01

    Lacunar transient ischemic attack (lacunar TIA) may have been underestimated because of diagnostic difficulties. The aim of our study was to classify TIAs by etiologic subtypes, especially using defined criteria for diagnosis of lacunar TIA and clarify clinical characteristics of lacunar TIA.105 TIA patients out of consecutive 1,244 patients with acute ischemic stroke admitted to our hospital between January 2007 and June 2010 were enrolled in the present study. TIA was defined as an acute focal neurological deficit lasting less than 24 hours, suspected to be of cerebrovascular origin regardless of ischemic lesions on MRI. TIAs were classified to 5 etiologic subtypes; cardioembolic TIA, atherothrombotic TIA, lacunar TIA, other etiologies, and undetermined etiology and clinical characteristics in each subtype and the incidence of recurrent stroke after TIA were investigated. Lacunar TIA was diagnosed if the following criteria were fulfilled; presence of lacunar infarct on MRI and/or the presence of unilateral dysfunction of at least two of three body parts (face, arm, leg) in the absence of cortical dysfunction presumed due to subcortical ischemia. Absence of cardiac sources of embolism and large artery atherosclerosis. In 105 patients with TIA, lacunar TIA was the most frequent etiology (31%) followed by cardioembolic TIA (27%), atherothrombotic TIA (19%), undetermined etiology (18%), and other etiologies (6%). In patients with lacunar TIA, history of repeated TIA was more frequent and systolic blood pressure on admission was higher significantly than in cardioembolic TIA. Six of 105 patients had experienced recurrent stroke after TIA during admission. Among these 6 patients, 3 patients were diagnosed as lacunar infarctions. Lacunar TIA was most common TIA subtype in the present study. It is critical to identify lacunar TIA on admission because some patients with lacunar TIAs experience early recurrent stroke. (author)

  18. Electroacupuncture preconditioning reduces cerebral ischemic injury via BDNF and SDF-1α in mice

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    Kim Ji Hyun

    2013-01-01

    Full Text Available Abstract Background This study was designed to determine if electroacupuncture (EA preconditioning improves tissue outcome and functional outcome following experimentally induced cerebral ischemia in mice. In addition, we investigated whether the expression of brain-derived neurotrophic factor (BDNF and stromal cell derived factor-1α (SDF-1α and infarct volume were related with improvement in neurological and motor function by interventions in this study. Methods After treatment with EA at the acupoints ‘Baihui (GV20’ and ‘Dazhui (GV14’ for 20 min, BDNF was assessed in the cortical tissues based on Western blot and the SDF-1α and vascular endothelial growth factor (VEGF levels in the plasma determined by ELISA. To assess the protective effects of EA against ischemic injury, the mice received once a day 20 min EA preconditioning for three days prior to the ischemic event. Focal cerebral ischemia was then induced by photothrombotic cortical ischemia. Infarct volumes, neurobehavioral deficit and motor deficit were evaluated 24 h after focal cerebral ischemia. Results The expression of BDNF protein increased significantly from 6 h, reaching a plateau at 12 h after the end of EA treatment in the cerebral cortex. Furthermore, SDF-1α, not VEGF, increased singnificantly from 12 h to 48 h after EA stimulation in the plasma. Moreover, EA preconditioning reduced the infarct volume by 43.5% when compared to control mice at 24 h after photothrombotic cortical ischemia. Consistent with a smaller infarct size, EA preconditioning showed prominent improvement of neurological function and motor function such as vestibule-motor function, sensori-motor function and asymmetric forelimb use. The expression of BDNF colocalized within neurons and SDF-1α colocalized within the cerebral vascular endothelium was observed throughout the ischemic cortex by EA. Conclusions Pretreatment with EA increased the production of BDNF and SDF-1α, which elicited

  19. Biochemical signaling by remote ischemic conditioning of the arm versus thigh: Is one raise of the cuff enough?

    Directory of Open Access Journals (Sweden)

    Cameron Dezfulian

    2017-08-01

    Full Text Available Remote Ischemic Conditioning (RIC, induced by brief cycles of ischemia and reperfusion, protects vital organs from a prolonged ischemic insult. While several biochemical mediators have been implicated in RIC's mechanism of action, it remains unclear whether the localization or “dose” of RIC affects the extent of protective signaling. In this randomized crossover study of healthy individuals, we tested whether the number of cycles of RIC and its localization (arm versus thigh determines biochemical signaling and cytoprotection. Subjects received either arm or thigh RIC and then were crossed over to receive RIC in the other extremity. Blood flow, tissue perfusion, concentrations of the circulating protective mediator nitrite, and platelet mitochondrial function were measured after each RIC cycle. We found that plasma nitrite concentration peaked after the first RIC cycle and remained elevated throughout RIC. This plasma nitrite conferred cytoprotection in an in vitro myocyte model of hypoxia/reoxygenation. Notably, though plasma nitrite returned to baseline at 24 h, RIC conditioned plasma still mediated protection. Additionally, no difference in endpoints between RIC in thigh versus arm was found. These data demonstrate that localization and “dose” of RIC does not affect cytoprotection and further elucidate the mechanisms by which nitrite contributes to RIC-dependent protection.

  20. Pediatric ischemic stroke due to dengue vasculitis.

    Science.gov (United States)

    Nanda, Subrat Kumar; Jayalakshmi, Sita; Mohandas, Surath

    2014-10-01

    Dengue infection is an important arboviral infection in southeast Asia, especially in India. Neurological manifestations of dengue are increasingly recognized. We report an ischemic stroke due to dengue vasculitis in an 8-year-old child. We present a girl with a short febrile illness followed by episodic severe headache, with gradually progressive hemiparesis and visual impairment. Her brain magnetic resonance imaging revealed multiple infarctions in the anterior and posterior circulation. The magnetic resonance angiogram revealed irregular narrowing of bilateral middle cerebral arteries, right anterior cerebral artery, left posterior cerebral, and bilateral vertebral arteries suggestive of vasculitis. Her dengue serology was strongly positive for immunoglobulin M with 68.9 panbio units. The rest of the evaluation for pediatric stroke was unremarkable. She was treated with intravenous followed by oral corticosteroids and recovered totally with resolution of vasculitis on magnetic resonance angiogram over the next 3 months. This child illustrates possible immune-mediated vasculitis caused by dengue infection which is rather a rare presentation in a child who subsequently recovered well. One should consider dengue in childhood strokes in endemic regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Clinical study on transient ischemic attack

    International Nuclear Information System (INIS)

    Takusagawa, Yoshihiko; Fujiwara, Yasuhiro; Ichiki, Ken; Suga, Takeshi; Nishigaki, Shinichi

    1986-01-01

    The purpose of this study was to neuroradiologically elucidate the mechanism by which transient ischemic attack (TIA) occurs. A total of 65 patients with TIA, including 52 with TIA in the internal carotid artery (Group I) and 13 with TIA in the vertebrobasilar artery (Group II), underwent computed tomography (CT) and cerebral angiography (CAG). In Group I, CAG revealed normal findings in 25 patients, extracranial lesions in 14, intracranial lesions in 11, and mixed extra- and intra-cranial lesions in 2; and the corresponding figures for Group II were 8, 4, 1 and 0, respectively. CT findings in Groups I and II included: normal findings in 27 and 9 patients, atrophied cerebrum and dilated cerebral ventricle in 7 and 2, TIA-unrelated infarction in 5 and one, and TIA-related infarction in 15 and one, respectively. In the 15 patients with TIA-related infarction in Group I, 10 had infarction in the basal cell nucleolus and the other 5 had widespread infarction extending to the area under the cortex. The latter 5 patients had cerebral infarction, and showed recanalization of the vessels. This finding may support the theory of ''microembolus'' as a possible cause of TIA. (Namekawa, K.)

  2. Radiology of ischemic strokes in children

    International Nuclear Information System (INIS)

    Raybaud, C.A.; Jiddane, M.; Livet, M.O.; Pinsard, N.

    1985-01-01

    Arterial ischemic strokes are a relatively frequent diagnostic occurrence in pediatric neuroradiology. They occur mostly in three main etiologic contexts: 1) congenital heart disease; 2) neonatal distress; 3) infections, focal or general inducing vasculitis, but many cases are considered as idiopathic. The positive diagnosis is made by CT; in neonates, however, ultrasound appears as a promising tool. The CT features are basically similar at that age and in adults, although the site of the infarct may result from pathologies more particular to children (e.g. basal ganglia infarction due to arteritis of the carotid syphon and its branches). Infarcts may be multiple and also more frequently hemorrhagic at that age, the homorrhagic phenomena affecting only the gray matter except in young infants in which the subcortical white matter may be affected also. Anatomical sequels include focal atrophy and asymmetry of the brain. Data regarding the etiology can be gathered from angiography which may show the degree of impairment of the arterial bed, its extent, the collateral blood supply and the morphological type of arterial lesion responsible for the cerebral damage. The most particular picture at that age is that of the often diffuse vasculitis, with its various expressions (segmental narrowing of the lumen, dissecting aneurysm, string-of-beads appearance). (orig.)

  3. Radiology of ischemic strokes in children

    International Nuclear Information System (INIS)

    Raybaud, C.A.; Livet, M.O.; Jiddane, M.; Pinsard, N.

    1985-01-01

    Arterial ischemic strokes are a relatively frequent diagnostic occurrence in pediatric neuroradiology. They occur mostly in three main etiologic contexts: 1) congenital heart disease; 2) neonatal distress; 3) infections, focal or general inducing vasculitis, but many cases are considered idiopathic. The positive diagnosis is made by CT; in neonates, however, ultrasound appears as a promising tool. The CT features are basically similar at that age and in adults, although the site of the infarct may result from pathologies more particular to children (e.g. basal ganglia infarction due to arteritis of the carotid siphon and its branches). Infarcts may be multiple and also more frequently hemorrhagic at that age, the hemorrhagic phenomena affecting only the gray matter except in young infants in which the subcortical white matter may be affected also. Anatomical sequels include focal atrophy and asymmetry of the brain. Data regarding the etiology can be gathered from angiography which may show the degree of impairment of the arterial bed, its extent, the collateral blood supply and the morphological types of arterial lesion responsible for the cerebral damage. The most particular picture at that age is that of the often diffuse vasculitis, with its various expressions (segmental narrowing of the lumen, dissecting aneurysm, string-of-beads appearance)

  4. Cardiac MRI in ischemic heart disease

    International Nuclear Information System (INIS)

    Ishida, Masaki; Kato, Shingo; Sakuma, Hajime

    2009-01-01

    Considerable progress has been made in cardiac magnetic resonance imaging (MRI). Cine MRI is recognized as the most accurate method for evaluating ventricular function. Late gadolinium-enhanced MRI can clearly delineate subendocardial infarction, and the assessment of transmural extent of infarction on MRI is widely useful for predicting myocardial viability. Stress myocardial perfusion MRI allows for detection of subendocardial myocardial ischemia, and the diagnostic accuracy of stress perfusion MRI is superior to stress perfusion single-photon emission computed tomography in patients with multivessel coronary artery disease (CAD). In recent years, image quality, volume coverage, acquisition speed and arterial contrast of 3-dimensional coronary magnetic resonance angiography (MRA) have been substantially improved with use of steady-state free precession sequences and parallel imaging techniques, permitting the acquisition of high-quality, whole-heart coronary MRA within a reasonably short imaging time. It is now widely recognized that cardiac MRI has tremendous potential for the evaluation of ischemic heart disease. However, cardiac MRI is technically complicated and its use in clinical practice is relatively limited. With further improvements in education and training, as well as standardization of appropriate study protocols, cardiac MRI will play a central role in managing patients with CAD. (author)

  5. Genetics of Dyslipidemia and Ischemic Heart Disease.

    Science.gov (United States)

    Sharma, Kavita; Baliga, Ragavendra R

    2017-05-01

    Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

  6. Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.

    Science.gov (United States)

    Gelderblom, Mathias; Melzer, Nico; Schattling, Benjamin; Göb, Eva; Hicking, Gordon; Arunachalam, Priyadharshini; Bittner, Stefan; Ufer, Friederike; Herrmann, Alexander M; Bernreuther, Christian; Glatzel, Markus; Gerloff, Christian; Kleinschnitz, Christoph; Meuth, Sven G; Friese, Manuel A; Magnus, Tim

    2014-11-01

    Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke. © 2014 American Heart Association, Inc.

  7. Granuloma anular: distribuição tecidual dos dendrócitos dérmicos fator XIIIa+, das células dérmicas trombomodulina+ e de macrófagos CD68+ Granuloma annulare: tissue distribution of factor XIIIa+ dermal dendrocytes, thrombomodulin+ dermal cells and CD68+ macrophages

    Directory of Open Access Journals (Sweden)

    Claudia Regina Wanderley Soub

    2003-06-01

    expresses the pro-coagulation factor XIIIa, while others express the anti-coagulation cofactor thrombomodulin. These cells can be involved in inflammatory and reparative tissue events. OBJETIVES: We investigated the participation of factor XIIIa+ dermal cells and thrombomodulin+ (TM+ dermal cells in the histopathological picture of granuloma annulare which is characterized by collagen necrobiosis and macrophagic infiltrate. METHODS: The histopathological picture of granuloma annulare observed in 23 skin biopsies was classified according to presence of complete or incomplete collagen degeneration and distribution of dermal infiltrate. Factor XIIIa+ dermal dendrocytes and thrombomodulin+ dermal cells were recognized by specific antibodies applied in immunohistochemical protocols; a macrophage marker (CD68 was also used. Distribution of distinct cell subsets were observed and semiquantitative analysis performed. RESULTS: Factor XIIIa+ dendrocytes were rarely detected in the lesion while thrombomodulin+ and CD68+ cells represented a considerable part of cell infiltrate. They were seen at its periphery (palisade arrangement, among degenerated collagen or diffusely distributed. A tendency was noted for association between higher semiquantification of thrombomodulin+ cells and both lower semiquantification of FXIIIa+ dendrocytes and histological type II. Dermal dendrocyte hyperplasia around the lesion was detected. CONCLUSION: The different tissue distribution of the FXIIIa+ cells and TM+ cells could reflect their distinct and complementary roles in the recovery of dermal tissue and in the lesion evolutive process in granuloma annulare.

  8. Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

    OpenAIRE

    Zun-Jing Liu; Wei Liu; Lei Liu; Cheng Xiao; Yu Wang; Jing-Song Jiao

    2013-01-01

    Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPAR ? agonist in that it upregulated PPAR ? expression and PPAR ? -PPRE binding activity. Administration of curcumin markedly dec...

  9. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L. [University of Colorado Anschutz School of Medicine, Department of Radiology, Aurora, CO (United States); Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Armstrong-Wells, Jennifer [University of Colorado Anschutz School of Medicine, Department of Pediatrics (Neurology) and OB/GYN, Aurora, CO (United States); University of Colorado Hemophilia and Thrombosis Center, Aurora, CO (United States)

    2016-01-15

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm{sup 3} vs. 36,995 mm{sup 3}; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10{sup -6} mm{sup 2}/s vs. 611 x 10{sup -6} mm{sup 2}/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  10. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

    International Nuclear Information System (INIS)

    Stence, Nicholas V.; Mirsky, David M.; Deoni, Sean C.L.; Armstrong-Wells, Jennifer

    2016-01-01

    Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm 3 vs. 36,995 mm 3 ; P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 x 10 -6 mm 2 /s vs. 611 x 10 -6 mm 2 /s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis. (orig.)

  11. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

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    S. I. Shkrobot

    2018-02-01

    Full Text Available Objectives. The aim of the present study was to clarify clinical neurological characteristics and different ischemic stroke subtypes unfavorable course predictors in acute phase. Material and Methods. 482 patients with different ischemic stroke subtypes were observed. Among them there were 125 (25.9 % with cardioembolic infarct (CEI, 119 (24.7 % with large artery atherosclerosis (LAAS infarct, 122 (25.3 % with lacunar stroke (LAC, 116 (24.1 % with stroke of undetermined etiology (UDE. The comparative analysis of clinical picture was performed. The predictors of unfavorable course of acute phase were established. Results. We have found out that severe neurological deficit, high mortality and the worst functional outcome during the first 14 days were observed in patients with CEI and LAAS. The highest frequency of early neurological deterioration (END was detected at LAC (in 22.7 % of patients. There was a relationship between END and presence of transient ischemic attack (TIA in past medical history, the level of systolic blood pressure (SBP at the beginning of the disease and the degree of carotid arteries stenosis on the side of lesion. The patients with LAC had mild neurological deficit and better prognosis compared with other ischemic stroke subtypes. Among the clinical factors that have impact on the CEI, LAAS and UDE acute phase course were: the size of lesion, the level of consciousness on the 1st day, the baseline SBP, patient’s age. At LAAS, the presence of transient ischemic attack (TIA in past medical history and low SBP in the onset of the disease (less than140 mm Hg has an additional prognostic value for an unfavorable functional outcome. The severity of LAC in acute period depended on its localization and size. Localization of LAC in the internal capsule, thalamus and pons were characterized by the highest severity. Conclusions. Clinical neurological features of ischemic stroke depend on its subtype and have some prognostic value

  12. Health behavior of patients with ischemic heart disease

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    Paweł Węgorowski

    2017-06-01

    Full Text Available Admission By analyzing the available scientific literature, it is possible to define ischemic heart disease as a set of disease symptoms that are a consequence of a chronic state of imbalance between the ability to supply nutrients and oxygen and the real need of myocardial cells for these substances. Adapting life-style behaviors to healthy living is a priority to prevent the onset and development of cardiovascular disease, especially ischemic heart disease, Purpose of research The aim of the study is to determine the health behavior of patients with ischemic heart disease. Materials and methods The study was conducted from 01.08.2015 to 28.12.2015 in a group of 35 people (15 women and 20 men. The research method used in the work is a diagnostic survey, the research technique used was a survey of its own author. Conclusions By analyzing the data collected, it is important to note that patients with coronary heart disease are often associated with health problems such as hypertension, diabetes and abnormal weight. The nutritional habits of the subjects studied can be described as abnormal, particularly the excessive intake of oily meat and too little fish intake. It has also been observed that most of the patients studied have familial predisposition to ischemic heart disease. Discussion Heart attacks occur mostly in people with obesity, diabetes and atherosclerosis. It is also closely related to ischemic heart disease. The health behaviors of patients suffering from Ischemic Heart Disease are moderately satisfactory and therefore the role of a nurse practitioner as a health educator is very difficult but essential in the prevention of ischemic heart disease.

  13. Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

    Science.gov (United States)

    Andrés-Hernando, Ana; Altmann, Christopher; Ahuja, Nilesh; Lanaspa, Miguel A.; Nemenoff, Raphael; He, Zhibin; Ishimoto, Takuji; Simpson, Pete A.; Weiser-Evans, Mary C.; Bacalja, Jasna

    2011-01-01

    Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury. PMID:21677145

  14. Proteção funcional da enzima heme-oxigenase-1 na lesão renal aguda isquêmica e tóxica Protección funcional de la enzima heme-oxigenasa-1 en la lesión renal aguda isquémica y tóxica Functional protection of heme-oxygenase-1 enzyme in ischemic and toxic acute kidney injury

    Directory of Open Access Journals (Sweden)

    Cassiane Dezoti

    2009-01-01

    estudio demuestran que la isquemia y la PmxB inducen AKL por la elevación de los peróxidos urinarios. El inductor de HO-1 atenuó la lesión en ambos modelos por atenuación del mecanismo redox.OBJECTIVE: To investigate the functional protection of heme-oxygenase-1 enzyme (HO-1 when using its inducer (Hemin and inhibitor (zinc protoporphyrin-ZnPP in ischemic and toxic acute kidney injury by Polymixin B in mice. MATERIALS: Adult male Wistar mice divided into 8 groups were used: SHAM (control, Ischemic (Isq, Isq+Hemin (Inducer of H0-1, Isq+ZnPP (inhibitor of H0-1, SALINA (control, Polimyxin B (PmxB, PmxB+Hemin, PmxB+ZnPP. METHOD: Analysis consists of Jaffé (creatinine clearance [crCl] and FOX-2 (urinary peroxides [UP]. RESULTS: Thirty minutes renal ischemia and its treatment with PmxB reduced the crCl and maintained urinary output. Urinary peroxide levels increased in both injuries. The administration of the inducer of H0-1 resulted in improvement in renal function and reduction in the levels of urinary peroxide. CONCLUSIONS: Findings indicated that ischemia and PmxB induce LAR (acute kidney injury [AKI] by elevating the levels of urinary peroxide. The HO-1 inducer ameliorated the injury in both animal models through redox mechanism.

  15. Potential protective role of hydrogen against cisplatininduced side ...

    African Journals Online (AJOL)

    Potential protective role of hydrogen against cisplatininduced side effects during chemotherapy: A mini-review of a novel hypothesis for antagonism of hydrogen. ... Molecular hydrogen has been shown to have therapeutic effects against damage to various organs (especially kidney, brain and liver) caused by ischemic ...

  16. Predicting Long-term Ischemic Events Using Routine Clinical Parameters in Patients with Coronary Artery Disease: The OPT-CAD Risk Score.

    Science.gov (United States)

    Han, Yaling; Chen, Jiyan; Qiu, Miaohan; Li, Yi; Li, Jing; Feng, Yingqing; Qiu, Jian; Meng, Liang; Sun, Yihong; Tao, Guizhou; Wu, Zhaohui; Yang, Chunyu; Guo, Jincheng; Pu, Kui; Chen, Shaoliang; Wang, Xiaozeng

    2018-06-05

    high-risk (≥151 points) patients were 1.6%, 5.5%, and 15.0%, respectively. Compared to GRACE score, OPT-CAD score had a better discrimination in predicting ischemic events and all-cause mortality (ischemic events: 0.72 vs 0.65, all-cause mortality: 0.79 vs 0.72, both Pmanagement of antiplatelet therapy for patients with CAD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Protective effect of atorvastatin on radiation-induced endothelial cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Xinze, Ran; Huaien, Zheng; Fengchao, Wang; Xi, Ran; Aiping, Wang; Jing, Han; Yanqi, Zhang; Jun, Chen [Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing (China)

    2009-04-15

    Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 {mu}mol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

  18. Protective effect of atorvastatin on radiation-induced endothelial cell injury

    International Nuclear Information System (INIS)

    Ran Xinze; Zheng Huaien; Wang Fengchao; Ran Xi; Wang Aiping; Han Jing; Zhang Yanqi; Chen Jun

    2009-01-01

    Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 μmol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

  19. Gender and post-ischemic recovery of hypertrophied rat hearts

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    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  20. Neuroradiological study of transient ischemic attack

    Energy Technology Data Exchange (ETDEWEB)

    Takusagawa, Yoshihiko; Fujiwara, Yasuhiro; Ichiki, Ken; Suga, Takeshi; Nishigaki, Shinichi

    1986-08-01

    Fifty-two patients with carotid TIAs and thirteen patients with vertebrobasilar TIAs were investigated by angiography and computed tomography. TIA was diagnosed by clinical symptoms in accordance with the criteria for TIA of the Joint Committee for Stroke Facilities in the U.S.A. (1974). The 65 patients with TIAs included 49 males and 16 females with average age of 63.5 years old at the initial episode of TIA. As for the diseases associated with TIA, hypertension (51 %), diabetes mellitus (15 %) and ischemic heart diseases (11 %) were the major disorders. Atrial fibrillation was observed in 2 cases. Intervals from last TIA attack to angiography were less than 7 days in 22 cases, 8 -- 30 days in 19 cases, 1 -- 4 monthes in 14 cases and more than 4 monthes in 10 cases, respectively. The cases in which angiography was done earlier after attacks displayed more abnormal findings. In 52 patients with caroted TIAs the artherosclerotic change of extracranial portion of the internal carotid artery was found in 14 cases (27 %), that of intracranial portion of the artery in 11 cases (21 %) and both lesions in 2 cases (4 %). On the other hand, in 13 patients with vertebrobasilar TIAs, this change was observed in 4 cases at the extracranival potion and in 1 case at the intracranial potion (siphon) of the internal carotid artery. Abnormal CT findings were found in 29 of 65 patients, namely 9 had ventricular dilatation and brain atrophy, 6 had cerebral infarction which was not associated with associated with symptoms of TIA. In carotid TIAs, Cerebral infarction was associated with symptoms of TIAs in 15 cases, namely 10 had a small low density area in the basal ganglia near the internal capsule and 5 had a low density area in the cortical or subcortical region. All of these 5 cases had cerebral embolism, which recanalized after attacks. (J.P.N.).

  1. Neuroradiological study of transient ischemic attack

    International Nuclear Information System (INIS)

    Takusagawa, Yoshihiko; Fujiwara, Yasuhiro; Ichiki, Ken; Suga, Takeshi; Nishigaki, Shinichi

    1986-01-01

    Fifty-two patients with carotid TIAs and thirteen patients with vertebrobasilar TIAs were investigated by angiography and computed tomography. TIA was diagnosed by clinical symptoms in accordance with the criteria for TIA of the Joint Committee for Stroke Facilities in the U.S.A. (1974). The 65 patients with TIAs included 49 males and 16 females with average age of 63.5 years old at the initial episode of TIA. As for the diseases associated with TIA, hypertension (51 %), diabetes mellitus (15 %) and ischemic heart diseases (11 %) were the major disorders. Atrial fibrillation was observed in 2 cases. Intervals from last TIA attack to angiography were less than 7 days in 22 cases, 8 ∼ 30 days in 19 cases, 1 ∼ 4 monthes in 14 cases and more than 4 monthes in 10 cases, respectively. The cases in which angiography was done earlier after attacks displayed more abnormal findings. In 52 patients with caroted TIAs the artherosclerotic change of extracranial portion of the internal carotid artery was found in 14 cases (27 %), that of intracranial portion of the artery in 11 cases (21 %) and both lesions in 2 cases (4 %). On the other hand, in 13 patients with vertebrobasilar TIAs, this change was observed in 4 cases at the extracranival potion and in 1 case at the intracranial potion (siphon) of the internal carotid artery. Abnormal CT findings were found in 29 of 65 patients, namely 9 had ventricular dilatation and brain atrophy, 6 had cerebral infarction which was not associated with associated with symptoms of TIA. In carotid TIAs, Cerebral infarction was associated with symptoms of TIAs in 15 cases, namely 10 had a small low density area in the basal ganglia near the internal capsule and 5 had a low density area in the cortical or subcortical region. All of these 5 cases had cerebral embolism, which recanalized after attacks. (J.P.N.)

  2. Robotic exoskeleton assessment of transient ischemic attack.

    Directory of Open Access Journals (Sweden)

    Leif Simmatis

    Full Text Available We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA. A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS score, Chedoke-McMaster Stroke Assessment (CMSA of the arm, the Behavioural Inattention Test (BIT, the Purdue pegboard test (PPB, and the Montreal Cognitive Assessment (MoCA. Age-related white matter change (ARWMC, prior infarction and cella-media index (CMI were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5% showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5% participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.

  3. Robotic exoskeleton assessment of transient ischemic attack.

    Science.gov (United States)

    Simmatis, Leif; Krett, Jonathan; Scott, Stephen H; Jin, Albert Y

    2017-01-01

    We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.

  4. Spectroscopic photoacoustics for assessing ischemic kidney damage

    Science.gov (United States)

    Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

    2018-02-01

    Ischemic reperfusion injuries (IRIs) are caused by return of blood to a tissue or organ after a period without oxygen or nutrients. Damage in the microvasculature causes an inflammatory response and heterogeneous scarring, which is associated with an increase in collagen in the extracellular matrix. Although most often associated with heart attacks and strokes, IRI also occurs when blood reperfuses a transplanted organ. Currently, monitoring for IRI is limited to biopsies, which are invasive and sample a limited area. In this work, we explored photoacoustic (PA) biomarkers of scarring. IRI events were induced in mice (n=2) by clamping the left renal artery, then re-establishing flow. At 53 days post-surgery, kidneys were saline perfused and cut in half laterally. One half was immediately imaged with a VevoX system (Fujifilm-VisualSonics, Toronto) in two near infrared ranges - 680 to 970 nm (NIR), and 1200 to 1350 nm (NIR II). The other half was decellularized and then imaged at NIR and NIR II. Regions of interest were manually identified and analyzed for each kidney. For both cellularized and decellularized samples, the PA signal ratio based on irradiation wavelengths of 715:930 nm was higher in damaged kidneys than for undamaged kidneys (p collagen in the NIR II range, while healthy kidneys did not. Collagen rich spectra were more apparent in decellularized kidneys, suggesting that in the cellularized samples, other components may be contributing to the signal. PA imaging using spectral ratios associated with collagen signatures may provide a non-invasive tool to determine areas of tissue damage due to IRIs.

  5. Rescuing the ischemic penumbra: Our experience

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    Milosavljević Tamara

    2013-12-01

    Full Text Available Objectives: Over one million strokes per year are occurring in Europe. Brain stroke is one of the most important death and disability causes in Europe and USA. The main role of perfusion is to determine the border of insult core and ischemic penumbra. Penumbra can be saved with thrombolytic therapy but core have irreversible injuries and represent death of brain cells. Aim: to determine the role of CT brain perfusion in cases of acute brain stroke and following thrombolytic therapy. Methods: We examined 64 patients with acute brain stroke who received thrombolytic therapy after that. All patients were examining on 16 MDCT with 50 ml of iodine contrast agent following the standard procedure for CT perfusion. Patients were 34 male and 30 female with middle age of 64 years. MRI was made after thrombolytic therapy and compare with perfusion results before therapy. Results: Using an artery and a vein as reference three parameters were measured - blood flow (CBF, blood volume (CBV and mean transit time (MTT, for each patient. Hemorrhagic was find in 9 (14.01% patients after thrombolytic therapy. 4 (6.25% other patients develop new stroke of same but mostly other side of brain. 8 (12.50% more patients finished lethally. From other 42 patients with thrombolytic therapy we can positively say that in 31 (48.44% patients penumbra was rescued. For other 11 (17.19% stroke was same size like firstly involved core and penumbra but not bigger. Conclusion: CT perfusion plays major role by showing a curable parts of tissue in brain strokes.

  6. Global DNA methylation of ischemic stroke subtypes.

    Directory of Open Access Journals (Sweden)

    Carolina Soriano-Tárraga

    Full Text Available Ischemic stroke (IS, a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA, small-artery disease (SAD, and cardio-aortic embolism (CE. A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204 were included, distributed across 3 IS subtypes: LAA (78/281, 59/204, SAD (97/281, 53/204, and CE (106/281, 89/204. In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.

  7. Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management

    Directory of Open Access Journals (Sweden)

    Berry S

    2017-09-01

    Full Text Available Shauna Berry,1 Weijie V Lin,2 Ama Sadaka,1 Andrew G Lee1–7 1Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 3Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch (UTMB, Galveston, TX, USA; 4Department of Ophthalmology, 5Department of Neurology, 6Department of Neurosurgery, Weill Cornell Medicine, Houston, TX, USA; 7Department of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Nonarteritic anterior ischemic optic neuropathy (NAION is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea. The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION. Keywords: anterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy, ischemic optic neuropathy

  8. Pharmaceutical Sponsorship Bias Influences Thrombolytic Literature in Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Ryan P Radecki

    2011-05-01

    Full Text Available Background: The efficacy of thrombolytic therapy for acute ischemic stroke remains controversial in Emergency Medicine and has not been fully endorsed by either the American College of Emergency Physicians or the American Academy of emergency medicine. A growing recognition exists of the influence of pharmaceutical sponsorship on the reported findings of published clinical trials. Sponsorship bias has been suggested as a potential criticism of the literature and guidelines favoring thrombolytic therapy. Objective: The objective of this study is to review the most influential literature regarding thrombolytic therapy for acute ischemic stroke and document the presence or absence of pharmaceutical sponsorship. Methods: A publication-citation analysis was performed to identify the most frequently cited articles pertaining to thrombolytic therapy for acute ischemic stroke. Identified articles were reviewed for disclosures of pharmaceutical funding. Results: Of the 20 most-cited articles pertaining to thrombolytic therapy for acute stroke, 17 (85% disclosed pharmaceutical sponsorship. These disclosures range from general sponsorship to direct employment of authors by pharmaceutical companies. Conclusion: An overwhelming predominance of the most influential literature regarding thrombolytic therapy for acute ischemic stroke is susceptible to sponsorship bias. This potential bias may provide a basis for physician concern regarding the efficacy and safety of thrombolytic therapy. Further, large, independent, placebo-controlled studies may be required to guide therapy and professional guidelines definitively for acute ischemic stroke. [West J Emerg Med. 2011;12(4:435–441.

  9. Relationship between hypertensive cerebral hemorrhage and ischemic lesions

    International Nuclear Information System (INIS)

    Yamaguchi, Shinya; Tsuchiya, Takashi; Yamaguchi, Takenori

    1991-01-01

    Patchy parenchymal lesions of increased intensity were frequently identified in patients with cerebral hemorrhage in T2-weighted image of high-fields MR imaging. We studied 64 patients with brain hemorrhage to determine the frequency and distribution of those lesions. We defined an area with high intensity in T2 weighted and low or iso-intensity area in T1 weighted images smaller than 1.5 cm in diameter to be 'ischemic lesion'. Ishemic lesions were found in 48 (75%) of all cases; in 25 (75%) of 32 patients with putaminal hemorrhage, in 15 (100%) of 15 with thalamic hemorrhage, in 3 (33%) of 9 with subcortical hemorrhage. Multiple ischemic lesions were more frequently seen in thalamic hemorrhage than in putaminal hemorrhage. Only 5 (10%) of 48 cases with associated ischemic lesions had a previous history related to those lesions. Multivariable regression analysis identified hypertension as the major predictor of the presence of ischemic lesions. Patients with brain hemorrhage frequently accompanied with incidental ischemic lesions, making it difficult to establish a guideline of blood pressure control for prevention of recurrent stroke. (author)

  10. Mortality study for a decade: ischemic stroke in the elderly.

    Directory of Open Access Journals (Sweden)

    Javier J. García Zacarías

    2014-09-01

    Full Text Available Cerebrovascular diseases are among the top three causes of death in Cuba and the world, about 80 % of these patients belong to Ischemic Stroke. The objective of this paper is to describe the clinical and developmental profile of patients who died of Ischemic Stroke. A descriptive, prospective research, cross- sectional study was made, the sample included all deaths from ischemic stroke at the University Hospital "Camilo Cienfuegos" Sancti Spiritus, between January 1st, 2001 and December 31, 2010, and persons over 60 years of age with necropsy performed. Atherothrombotic stroke was the most frequent category, the highest mortality rates were observed in persons over 80 years of age and in females, hypertension, ischemic heart disease and transient ischemic attack were the main significant medical history; most patients were admitted in the stroke unit and died in Middle Progressive Care, cerebral edema and intracranial hypertension and hypostatic bronchopne umonia were complications and specific main causes of most frequent death. Value of cerebral edema and hypostatic bronchopneumonia as clinical complications and causes of death in patients investigated is confirmed.

  11. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  12. Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure.

    Science.gov (United States)

    Foster, Gary P; Westerdahl, Daniel E; Foster, Laura A; Hsu, Jeffrey V; Anholm, James D

    2011-12-15

    Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure. Published by Elsevier B.V.

  13. Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients

    International Nuclear Information System (INIS)

    Kurata, Mie; Okura, Takafumi; Kumon, Yoshiaki; Tagawa, Masahiko; Watanabe, Hideaki; Miyazaki, Tatsuhiko; Higaki, Jitsuo; Nose, Masato; Nakahara, Toshinori

    2012-01-01

    Atherothrombosis is the primary pathophysiology that underlies ischemic cerebral infarction. Osteopontin (OPN) is produced in atherosclerotic lesions and is cleaved by activated thrombin. We hypothesized that the rupture or damage of an unstable atherosclerotic plaque increases plasma levels of thrombin-cleaved OPN (trOPN). This study included 90 patients who received carotid angioplasty with stenting (CAS), 23 patients with essential hypertension (EHT) and 10 patients who were treated with carotid endarterectomy (CEA). The CAS patient group included 36 patients that had pre- and post-operative blood tests, diffusion-weighted imaging (DWI) using cerebral MRIs and estimated thrombus debris within the protection device. Immunohistochemistry of CEA specimens revealed that trOPN was detected around intra-plaque vessels. The highest tertile of plasma trOPN levels in CAS patients was higher than trOPN levels in EHT patients. Post-operative trOPN levels were significantly higher in symptomatic compared with asymptomatic patients (P=0.003). New ipsilateral DWI-positive patients revealed higher post-operative trOPN levels (P=0.003) and a higher grade of thrombi (P<0.001) than DWI-negative patients. TrOPN may be a novel biomarker that reflects the atherothrombotic status in ischemic stroke. (author)

  14. Cardioprotective Effects of Pomegranate (Punica granatum) Juice in Patients with Ischemic Heart Disease.

    Science.gov (United States)

    Razani, Zahra; Dastani, Mostafa; Kazerani, Hamid Reza

    2017-11-01

    Ischemic heart disease is the leading cause of mortality worldwide. The purpose of this study was to evaluate the cardioprotective effects of pomegranate juice in patients with ischemic heart disease. One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each). During 5 days of hospitalization, in addition to the conventional medical therapies, the test groups received 220 mL pomegranate juice, daily. During the hospitalization period, the blood pressure, heart rate, as well as the intensity, occurrence, and duration of the angina were evaluated on a regular basis. At the end of the hospitalization period, the serum levels of malondialdehyde, interleukin-6, and tumor necrosis factor alpha were measured in all patients. The levels of serum troponin and high-sensitive C-reactive protein levels were also assayed in patients diagnosed with myocardial infarction. Pomegranate juice caused significant reductions in the intensity, occurrence, and duration of angina pectoris in patients with unstable angina. Consistently, the test patients had significantly lower levels of serum troponin and malondialdehyde. Other studied parameters did not change significantly. The results of this study suggest protective effects of pomegranate juice against myocardial ischemia and reperfusion injury. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke.

    Science.gov (United States)

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

  16. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    Directory of Open Access Journals (Sweden)

    Hailian Wang

    2016-01-01

    Full Text Available Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms.

  17. Is there any cardioprotective role of Taurine during cold ischemic period following global myocardial ischemia?

    Directory of Open Access Journals (Sweden)

    Gamsizkan Mehmet

    2011-03-01

    Full Text Available Abstract Background The aim of the present study was to investigate the cardioprotective effect of Taurine on the donor hearts during cold ischemic period. Methods 32 rats were divided into four groups (sham, taurine, ischemia, treatment group, 8 rats in each. All rats were fed with rat food for three weeks. Taurine and treatment groups were given a 200 mg/kg/day dose of Taurine by oral gavage besides rat feed. Cardiectomy was performed in all rats after three weeks. In ischemia and treatment groups, harvested hearts were kept in 0.9% sodium chloride at +4 degrees C for 5 hours. Tissue samples were taken from left ventricle in all groups. These samples were evaluated by histopathologic and biochemical examination. Results In the present study results of the biochemical and histopathological examination reveals the protective effects of Taurine. As a marker of lipid peroxidation, Malondialdehyde (MDA levels in ischemia group were significantly higher than both Sham and Taurine groups. MDA values were recorded; 3.62 ± 0.197 in the sham group, 2.07 ± 0.751 in the Taurine group, 9.71 ± 1.439 in the ischemia group and 7.68 ± 1.365 in the treatment group. MDA levels decreased in treatment group. (p Conclusion Taurine decreased myocardial damage during cold ischemic period following global myocardial ischemia.

  18. Combination of five clinical data as prognostic factors of mortality after ischemic stroke

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    Rizaldy Taslim Pinzon

    2017-04-01

    Age, high random blood glucose level, complications, metabolic encephalopathy risk and the use of ventilators are associated with mortality after ischemic stroke. The predictive mortality score can be used to assess the prognosis of patients with ischemic stroke.

  19. Elevated Plasma YKL-40 Levels and Ischemic Stroke in the General Population

    DEFF Research Database (Denmark)

    Kjaergaard, A.D.; Bojesen, S.E.; Johansen, J.S.

    2010-01-01

    inside the vessel wall. Methods: We measured plasma YKL-40 in 8,899 21- to 93-year-old participants of the Copenhagen City Heart Study 1991-1994 examination, and followed them for up to 18 years. Endpoints were ischemic stroke, ischemic cerebrovascular disease, myocardial infarction, and ischemic heart......% confidence interval, 11%-30%) for ischemic stroke, 16% (8%-24%) for ischemic cerebrovascular disease, 3% (-5%-11%) for myocardial infarction, and 7% (1%-12%) for ischemic heart disease. Interpretation: In the general population, elevated plasma YKL-40 levels are associated with increased risk of ischemic...... stroke and ischemic cerebrovascular disease, independent of plasma CRP levels. ANN NEUROL 2010;68:672-680...

  20. Radioisotope heart examination during exercise to diagnose ischemic heart disease

    International Nuclear Information System (INIS)

    Farsky, S.

    1986-01-01

    The radioisotope exercise test is discussed and its benefits characterized for the diagnosis of ischemic heart disease, namely the use of 99m Tc in scintiscanning heart ventricles and of 201 Tl in scintiscanning myocardial perfusion. The exercise ventricular function and perfusion scintigraphies are compared with the common exercise ECG examination, and their superior sensitivity and specificity emphasized. Considering the constraints of scintigraphic imaging, indications are outlined for patients including those with suspect serious ischemic heart disease in whom the exercise ECG test has been negative or inconclusive, patients with the so-called nondiagnostic ECG, patients with atypical symptoms, and healthy individuals for whom the exercise ECG test indicated with respect to their occupation has been positive. Both radionuclide imaging techniques are complementary and are shown to be valuable not only in improving the diagnosis of ischemic heart disease but also in identifying the high-risk patients in whom cardiac surgery is to be considered. (L.O.)

  1. Clinical effect of Dilazep on ischemic heart disease

    International Nuclear Information System (INIS)

    Tsuda, Takashi; Hayashi, Senji; Shibata, Akira; Hama, Hitoshi; Mitani, Tohru.

    1982-01-01

    Dilazep tablets (300 mg/day) were administered to 9 patients with ischemic heart disease for more than 2 months. Stress myocardial scintigraphy was performed before and after the treatment to examine the clinical effect of this drug on the heart. The improvement rate of subjective symptoms was 57% (4/7 cases). No significant difference was observed in double product by the ergometer before and after the treatment, nor were any significant changes observed in ST by Master's two-step exercise test in any patient. The pre- to posttreatment improvement rate of myocardial uptake, demonstrated by stress myocardial scintigraphy, was 89% (8/9 cases). Thus, Dilazep tablets seemed to increase the blood flow in the ischemic area of the myocardium during exercise in ischemic heart disease. (Chiba, N.)

  2. Intensive treadmill training in the acute phase after ischemic stroke

    DEFF Research Database (Denmark)

    Strømmen, Anna Maria; Christensen, Thomas; Jensen, Kai

    2016-01-01

    The aim of the study was to (a) assess the feasibility of intensive treadmill training in patients with acute ischemic stroke, (b) test whether physical activity of the legs during training increases with time, and (c) evaluate to what extent training sessions contribute toward the overall physical...... activity of these patients. Twenty hospitalized patients with acute ischemic stroke trained on a treadmill twice daily for 30 min for 5 days and on day 30. Physical activity was measured as activity counts (AC) from accelerometers. A total of 196 of 224 initiated training sessions were completed. Training...... with increasing number of days, with the median AC being 133% higher on day 5 than on day 1. AC in the paretic leg during 60 min of training constituted median 53% of the daytime AC. Early intensive treadmill training in acute ischemic stroke patients is thus feasible and contributes considerably toward...

  3. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    Science.gov (United States)

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. A Case Of Transient Ischemic Attack Presenting As Hemichroea

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    Hasan Hüseyin Özdemir

    2013-12-01

    Full Text Available Chorea is defined as; involuntary movements of the distal parts of limbs which have arrhythmic, rapid, bouncing or smooth, simple or complex properties. Choreiform movements occur when putamen, globus pallidus and subthalamic nucleus are affected. Chorea can be observed during the course of metabolic and vascular diseases, neurodegenerative or hereditary diseases. Chorea may be a rare symptom of cerebral hypoperfusion. Transient ischemic attack is an event that occurs in short term characterized by a temporary ischemia of brain. A wide variety of symptoms can be seen depending on the localization of cerebral hypoperfusion. Hemichorea is a very rare finding observed during transient ischemic attacks. In this article hemichorea in a case of symptomatic transient ischemic attack is discussed with relevant literature.

  5. Air Pollution and Ischemic Stroke Among Young Adults.

    Science.gov (United States)

    Yitshak Sade, Maayan; Novack, Victor; Ifergane, Gal; Horev, Anat; Kloog, Itai

    2015-12-01

    Studies have demonstrated consistent associations between cardiovascular illness and particulate matter (PM) stroke received less attention. We hypothesized that air pollution, an inflammation progenitor, can be associated with stroke incidence in young patients in whom the usual risk factors for stroke are less prevalent. We aimed to evaluate the association between stroke incidence and exposure to PM stroke between 2005 and 2012. Exposure assessment was based on a hybrid model incorporating daily satellite remote sensing data at 1-km spatial resolution. We performed case-crossover analysis, stratified by personal characteristics and distance from main roads. We identified 4837 stroke cases (89.4% ischemic stroke). Interquartile range of PM ischemic stroke and increases of interquartile range average concentrations of particulate matter ischemic stroke associated with PM among young adults. This finding can be explained by the inflammatory mechanism, linking air pollution and stroke. © 2015 American Heart Association, Inc.

  6. A rare cause of ischemic stroke: Intravasculer B cell lymphoma

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    Şeyma Çiftçi

    2014-08-01

    Full Text Available Intravascular B cell lymphoma is rare and an agressive form of large B cell lymphoma which can affect central nervous system. Because of its varied clinical symptoms and the absence of lymphadenopathy, it is generally diagnosed postmortem. Cerebral infarction due to occlusion of arteries can be seen as a rare clinical form of central nervous system involvement. Large artery atherosclerosis, cardiyoembolism and small artery occlusion are the important causes of ischemic stroke but no any cause is detected in %15-40 of all cases. In this report, with the discussion of a case with ischemia like encephalopathy and multiple cerebral ischemic lesions at different stages in cranial MRI which was diagnosed by the help of brain biopsy as a intravascular B cell lymphoma, it is aimed to take attention intravascular lymphoma as a rare cause of ischemic stroke.

  7. Ischemic colitis or melanosis coli: a case report

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    Nadeem Mohammed

    2007-09-01

    Full Text Available Abstract Background Melanosis Coli is described as black or brown discolouration of the mucosa of the colon. Its a benign condition, which arises from anthraquinone laxative abuse and has no symptoms of its own. The main importance of diagnosing Melanosis Coli correctly lies in the fact that if its extensive, there may be difficulty in differentiating it from ischemic colitis. Case presentation We present a case of extensive Melanosis Coli involving the whole of large bowel that appeared gangrenous. A sub total colectomy was performed on presumed diagnosis of ischemic bowel. Conclusion This report reminds the clinicians that extensive Melanosis Coli may mimic ischemic colitis and thus must be considered as a differential diagnosis.

  8. miRNAs as therapeutic targets in ischemic heart disease.

    Science.gov (United States)

    Frost, Robert J A; van Rooij, Eva

    2010-06-01

    Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

  9. Contemporary Management of Ischemic Mitral Regurgitation: a Review.

    Science.gov (United States)

    Sandoval, Yader; Sorajja, Paul; Harris, Kevin M

    2018-02-28

    Ischemic mitral regurgitation occurs relatively frequently in patients with coronary artery disease and is associated with an increased long term risk. The pathophysiology of ischemic mitral regurgitation is vexing, and poses both diagnostic and therapeutic challenges, leading to the need for a comprehensive, multidisciplinary approach. The management is largely focused on medical therapy, and for those eligible, coronary revascularization and/or cardiac resynchronization therapy may be considered. In select patients, mitral valve surgery or catheter-based therapy may be undertaken with careful consideration of the underlying pathophysiology, surgical risk, and expected long-term outcomes. The appropriate evaluation of patients with ischemic mitral regurgitation involves a careful multidisciplinary approach that carefully considers symptomatology, the etiology and severity of the mitral regurgitation, as well as the assessment of comorbidities and operative risk to individualize the care of these patients. Copyright © 2018. Published by Elsevier Inc.

  10. Anticoagulant treatment in patients with atrial fibrillation and ischemic stroke

    DEFF Research Database (Denmark)

    Brunner-Frandsen, Nicole; Dammann Andersen, Andreas; Ashournia, Hamoun

    2015-01-01

    BACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia, with a lifetime risk of 25%, and it is a well-known independent risk factor for ischemic stroke. Over the last 15 years, efforts have been made to initiate relevant treatment in patients with AF. A retrospective study...... was set up to clarify whether this effort has resulted in a decreased proportion of patients with known AF experiencing an ischemic stroke. METHODS: Patients admitted to the Department of Neurology, Vejle Hospital, Denmark, with ischemic stroke from January 1997 to December 2012 were included in the study....... RESULTS: A total of 4134 patients were included in the study. Overall, the yearly proportion of patients with known AF varied between 9% and 18%. No significant change was observed (P = .511). The proportion of patients with known AF treated with anticoagulants at the time of the stroke and the proportion...

  11. The effects of citicoline on acute ischemic stroke

    DEFF Research Database (Denmark)

    Overgaard, Karsten

    2014-01-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression...... lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute...... therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11...

  12. The Siblings With Ischemic Stroke Study (SWISS Protocol

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    Hardy John

    2002-02-01

    Full Text Available Abstract Background Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. Methods Screening at multiple clinical centers identifies patients (probands with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. Discussion Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members.

  13. Improvement of postoperative cognitive dysfunction and attention network function of patients with ischemic cerebrovascular disease via dexmedetomidine.

    Science.gov (United States)

    Zhang, Jingchao; Wang, Guoliang; Zhang, Fangxiang; Zhao, Qian

    2018-03-01

    The protective effect of dexmedetomidine on cognitive dysfunction and decreased attention network function of patients with ischemic cerebrovascular disease after stenting was investigated. Fifty-eight patients with ischemic cerebrovascular disease undergoing stenting in Guizhou Provincial People's Hospital were selected and randomly divided into control group (n=29) and dexmedetomidine group (n=29). The dexmedetomidine group was treated with dexmedetomidine before induced anesthesia, while the control group was given the same dose of normal saline; and the normal volunteers of the same age were selected as the normal group (n=29). At 3 days after operation, the levels of serum S100B and nerve growth factor (NGF) in each group were detected using the enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic factor (BDNF) was detected via western blotting. Montreal cognitive assessment (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive function and attention network function, and the effects of dexmedetomidine on cognitive function and attention network function were evaluated. The concentrations of serum S100B and NGF in dexmedetomidine group was lower than those in control group (Pfunction scores, attention scores, delayed memory scores, targeted network efficiency and executive control network efficiency in dexmedetomidine group were obviously higher than those in control group (Pcognitive function and attention network function of patients with ischemic cerebrovascular disease have a certain degree of damage, and the preoperative administration of dexmedetomidine can effectively improve the patient's cognitive dysfunction and attention network function after operation.

  14. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA{sub 2} activity

    Energy Technology Data Exchange (ETDEWEB)

    Takatani-Nakase, Tomoka, E-mail: nakase@mukogawa-u.ac.jp; Takahashi, Koichi, E-mail: koichi@mukogawa-u.ac.jp

    2015-07-17

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA{sub 2}, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death. - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA{sub 2} activity, leading to avoidance of non-apoptotic cell death.

  15. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA2 activity

    International Nuclear Information System (INIS)

    Takatani-Nakase, Tomoka; Takahashi, Koichi

    2015-01-01

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA 2 , which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death. - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA 2 activity, leading to avoidance of non-apoptotic cell death

  16. A prototypical Sigma-1 receptor antagonist protects against brain ischemia

    OpenAIRE

    Schetz, John A.; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W.

    2007-01-01

    Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this s...

  17. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

    Science.gov (United States)

    Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

    2017-10-01

    Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

  18. Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

    Directory of Open Access Journals (Sweden)

    Matthew A Schechter

    Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

  19. The Serotonin Transporter Gene Polymorphisms and Risk of Ischemic Stroke

    DEFF Research Database (Denmark)

    Mortensen, Janne Kærgård; Kraglund, Kristian Lundsgaard; Johnsen, Søren Paaske

    2018-01-01

    may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms...... and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA). MATERIALS AND METHODS: We conducted a case...

  20. Ischemic colitis after mesotherapy combined with anti-obesity medications.

    Science.gov (United States)

    Kim, Jong Bin; Moon, Won; Park, Seun Ja; Park, Moo In; Kim, Kyu-Jong; Lee, Jae Nam; Kang, Seong Joo; Jang, Lee La; Chang, Hee Kyung

    2010-03-28

    Mesotherapy and anti-obesity medications are gradually gaining worldwide popularity for purposes of body contouring and weight loss. Their adverse effects are various, but there is a tendency to disregard them. Ischemic colitis is one of the most common diseases associated with non-obstructive blood vessel disorders. However, there have been no case reports about the adverse effects resulting from mesotherapy only or in combination with anti-obesity medications. We report on an interesting case of ischemic colitis after mesotherapy combined with anti-obesity medications in a 39-year-old female who had no risk factors.

  1. Exploring lifestyle changes in women with ischemic heart disease

    DEFF Research Database (Denmark)

    Wagner, Malene; Nielsen, Karina; Jensen, Peter Errboe

    2017-01-01

    Ischemic heart disease (IHD) is a major cause of death for women worldwide, and thus it is important to focus on lifestyle changes to reduce the impact of the disease on women’s everyday lives. Nine women were interviewed using an explorative approach to describe women’s lifestyle changes after...... being diagnosed with IHD. Three major themes emerged; ‘Heart disease: A life-changing event’, ‘Social life – both inhibiting and promoting lifestyle changes’ and ‘Maintaining changes: An ongoing challenge and a conscious choice’. Ischemic heart disease caused anxiety, and the women strived to find...

  2. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    International Nuclear Information System (INIS)

    Park, Ju Young; Lee, In Ho; Song, Chang June; Hwang, Hee Youn

    2012-01-01

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  3. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Young; Lee, In Ho; Song, Chang June [Chungnam National University Hospital, Daejeon (Korea, Republic of); Hwang, Hee Youn [Eulji University Hospital, Daejeon(Korea, Republic of)

    2012-03-15

    A 57-year-old woman experienced bilateral acute ischemic optic neuropathy after spine surgery. Routine MR imaging sequence, T2-weighted image, showed subtle high signal intensity on bilateral optic nerves. A contrast-enhanced T1 weighted image showed enhancement along the bilateral optic nerve sheath. Moreover, diffusion-weighted image (DWI) and an apparent diffusion coefficient map showed markedly restricted diffusion on bilateral optic nerves. Although MR findings of T2-weighted and contrast enhanced T1-weighted images may be nonspecific, the DWI finding of cytotoxic edema of bilateral optic nerves will be helpful for the diagnosis of acute ischemic optic neuropathy after spine surgery.

  4. Ischemic Stroke Due to Cardiac Involvement: Emery Dreifuss Patient

    Directory of Open Access Journals (Sweden)

    Ersin Kasım Ulusoy

    2015-08-01

    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD is a hereditary disease. It is characterized by early-onset contractures, slowly progressive weakness, fatigue related to skapulo-humero-peroneal muscle weakness, cardiomyopathy which develops in adulthood and cardiac conduction system block. Cardiac involvement has a prognostic significance in patients with EDMD and even sudden cardiac death may be the first clinical presentation. In this article, an EDMD patient with ischemic stroke clinic who didn’t have regular cardiac follow-up was reported and the importance of the treatment of cardiac diseases which could play a role in ischemic stroke etiology and the implantation of pace-maker was mentioned.

  5. Mechanism of troponin elevations in patients with acute ischemic stroke

    DEFF Research Database (Denmark)

    Jensen, Jesper K.; Atar, Dan; Mickley, Hans

    2007-01-01

    the introduction of troponin in the diagnosis of acute myocardial infarction, this marker has been measured in a number of other conditions as well. One of these conditions is acute ischemic stroke, causing diagnostic dilemmas for clinicians. Because various electrocardiographic alterations have also been reported...... in these patients, it has been suggested that elevated troponin levels are somehow neurologically mediated, thus not caused by direct cardiac release. In conclusion, this review examines the available studies that systematically measured troponin in patients with acute ischemic stroke to properly interpret troponin...... elevations in these patients Udgivelsesdato: 2007-Mar-15...

  6. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  7. Incipient nonarteritic anterior ischemic optic neuropathy.

    Science.gov (United States)

    Hayreh, Sohan Singh; Zimmerman, M Bridget

    2007-09-01

    To describe the clinical entity of incipient nonarteritic anterior ischemic optic neuropathy (NAION). Cohort study. Fifty-four patients (60 eyes) seen in our clinic from 1973 through 2000. At their first visit to our clinic, all patients gave a detailed ophthalmic and medical history and underwent a comprehensive ophthalmic evaluation, color fundus photography, and fluorescein fundus angiography. At each follow-up visit (of 49 patients [55 eyes]), the same ophthalmic evaluation was performed, except for fluorescein fundus angiography. Clinical features of incipient NAION. Mean age (+/- standard deviation) of the patients was 58.7+/-15.9 years. Median follow-up time was 6.3 years (interquartile range [IQR], 2.1-8.5). At initial visit, all had optic disc edema (ODE) without any visual loss attributable to NAION. In 55%, the fellow eye had classic NAION; in 25%, incipient progressed to classic NAION (after a median time of 5.8 weeks [IQR, 3.2-10.1]); and in 20%, classic NAION developed after resolution of the first episode of incipient NAION. Patients with incipient, compared with classic, NAION had a greater prevalence of diabetes mellitus (Pheart disease (P = 0.046). Patients who progressed to classic NAION versus those who did not were significantly younger (P = 0.025), and their visual acuity worsened in 31% and 0%, respectively, and remained stable in 62% and 98%, respectively; in the eyes with progression, central (in 31%) and peripheral (in 77%) visual fields worsened compared with only 1 eye and 2 eyes, respectively, that did not (P = 0.01 and Pversus 9.6 weeks (IQR, 6.0-17.7) in those who did not progress. The results show that incipient NAION is a distinct clinical entity, with asymptomatic ODE and no visual loss attributable to NAION. When a patient seeks treatment with asymptomatic ODE, incipient NAION must be borne in mind as a strong possibility in those who have had classic NAION in the fellow eye, in diabetics of all ages, and in those with high risk

  8. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

  9. Silent ischemic brain lesions after transcatheter aortic valve replacement : lesion distribution and predictors

    NARCIS (Netherlands)

    Samim, Mariam; Hendrikse, Jeroen; van der Worp, H. Bart; Agostoni, Pierfrancesco; Nijhoff, Freek; Doevendans, Pieter A.; Stella, Pieter R.

    Silent ischemic brain lesions and ischemic stroke are known complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate the occurrence and distribution of TAVR-related silent ischemic brain lesions using diffusion-weighted magnetic resonance imaging (DWI). Consecutive

  10. Simultaneous Onset of Ischemic and Hemorrhagic Stroke Due To Intracranial Artery Dissection

    OpenAIRE

    Kim, Jong-Hoon; Jung, Young-Jin; Chang, Chul-Hoon

    2017-01-01

    Intracranial dissections commonly present as ischemic stroke and as hemorrhagic stroke. In general, while either ischemic stroke or hemorrhagic stroke may develop, the simultaneous onset of both may also occasionally occur. In this report, we present a case of simultaneous development of ischemic stroke and hemorrhagic stroke due to an intracranial artery dissection.

  11. Neuroprotective action of magneto-lasertherapy during the acute period of ischemic insult

    International Nuclear Information System (INIS)

    Samosyuk, N.I.; Ehkshi Il'ker

    2001-01-01

    New methods of ischemic insult treatment, in particular use of magneto-lasertherapy are described. Patients with different forms of ischemic insult were treated during acute period of it. Restoration of functions was registered in 80% of them. Clinical studies show considerable morphoprotective effect of this method and the expediency of its introduction in intensive ischemic insult therapy

  12. Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C{sub 2}H{sub 2} zinc finger protein

    Energy Technology Data Exchange (ETDEWEB)

    Han, D.; Zhang, C. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); Fan, W.J. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China); The Second Affiliated Hospital, University of South China, Hengyang City, Hunan Province (China); Pan, W.J.; Feng, D.M.; Qu, S.L.; Jiang, Z.S. [Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Post-doctoral Mobile Stations for Basic Medicine, University of South China, Hengyang City, Hunan Province (China)

    2014-10-31

    Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C{sub 2}H{sub 2} motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

  13. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  14. Novel therapy for renal protection.

    Science.gov (United States)

    Zarbock, Alexander; Milles, Kindgen

    2015-08-01

    Acute kidney injury (AKI) is a common and serious complication that significantly increases morbidity, mortality, and cost of care after surgery. In this article, we review recent studies that deal with strategies for renal protection and the prevention of AKI after surgery. A prerequisite for any prophylactic intervention is the identification of patients at risk for AKI or those with acute kidney damage before kidney function deteriorates. In this context, new biomarkers can help to detect cellular injury early. This way, a window for interventions can be opened. Several studies demonstrated the tissue-protective effect of remote ischemic preconditioning in various organs. There is clear evidence that use of balanced crystalloid fluids and the avoidance of hyperchloremic solutions for infusion therapy can reduce the incidence of AKI. Preliminary data show a protective effect if dexmedetomidine is used as a sedative agent following cardiac surgery. The most important intervention with proven efficacy to protect from AKI is aggressive hemodynamic stabilization. Early identification of patients at risk for AKI is crucial to apply any protective intervention. An improved perioperative management is required to prevent AKI. Although pharmacological therapies aiming to protect AKI are under evaluation, hemodynamic optimization and avoidance of nephrotoxic drugs are critical for perioperative patient.

  15. Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance.

    Science.gov (United States)

    Koronowski, Kevin B; Khoury, Nathalie; Saul, Isabel; Loris, Zachary B; Cohan, Charles H; Stradecki-Cohan, Holly M; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A

    2017-11-01

    Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain. We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions. Resveratrol-induced neuroprotection from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal Sirt1 , accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro. Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders. © 2017 American Heart Association, Inc.

  16. Whistleblower Protection

    Science.gov (United States)

    The Whistleblower Protection Enhancement Act of 2012 (WPA) and the Whistleblower Protection Act of 1989 Enhanced by the Act of 2012 provides protection rights for Federal employees against retaliation for whistleblowing activities.

  17. Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack

    Science.gov (United States)

    Brookes, Rebecca L.; Crichton, Siobhan; Wolfe, Charles D.A.; Yi, Qilong; Li, Linxin; Hankey, Graeme J.; Rothwell, Peter M.

    2018-01-01

    Background and Purpose— A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Methods— Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. Results— A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77; P=0.003). Conclusions— These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. PMID:29247141

  18. Radiation protection

    International Nuclear Information System (INIS)

    Koelzer, W.

    1975-01-01

    Physical and radiological terms, quantities, and units. Basic principles of radiation protection (ICRP, IAEA, EURATOM, FRG). Biological effects of ionizing radiation. Objectives of practical radiation protection. (HP) [de

  19. Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

    Science.gov (United States)

    Reddy, Manasa; Tawfik, Bernard; Gavva, Chakri; Yates, Sean; De Simone, Nicole; Hofmann, Sandra L; Rambally, Siayareh; Sarode, Ravi

    2016-12-01

    Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Endothelial Cells and Astrocytes: A Concerto en Duo in Ischemic Pathophysiology

    Directory of Open Access Journals (Sweden)

    Vincent Berezowski

    2012-01-01

    Full Text Available The neurovascular/gliovascular unit has recently gained increased attention in cerebral ischemic research, especially regarding the cellular and molecular changes that occur in astrocytes and endothelial cells. In this paper we summarize the recent knowledge of these changes in association with edema formation, interactions with the basal lamina, and blood-brain barrier dysfunctions. We also review the involvement of astrocytes and endothelial cells with recombinant tissue plasminogen activator, which is the only FDA-approved thrombolytic drug after stroke. However, it has a narrow therapeutic time window and serious clinical side effects. Lastly, we provide alternative therapeutic targets for future ischemia drug developments such as peroxisome proliferator- activated receptors and inhibitors of the c-Jun N-terminal kinase pathway. Targeting the neurovascular unit to protect the blood-brain barrier instead of a classical neuron-centric approach in the development of neuroprotective drugs may result in improved clinical outcomes after stroke.

  1. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    International Nuclear Information System (INIS)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar

    2015-01-01

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO x ) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO x concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group

  2. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Energy Technology Data Exchange (ETDEWEB)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar, E-mail: ghasemi@endocrine.ac.ir [Endocrine Physiology Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Endocrine Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-02-15

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO{sub x}) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO{sub x} concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  3. Relationship Between Ischemic Heart Disease and Sexual Satisfaction.

    Science.gov (United States)

    Ghanbari Afra, Leila; Taghadosi, Mohsen; Gilasi, Hamid Reza

    2015-06-10

    Ischemic heart disease is a life-threatening condition. Considerable doubts exist over the effects of this disease on patients' sexual activity and satisfaction. The aim of this study was to evaluate the relationship between ischemic heart disease and sexual satisfaction. In a retrospective cohort study, the convenience sample of 150 patients exposure with ischemic heart disease and 150 people without exposure it was drawn from Shahid Beheshti hospital, Kashan, Iran. Sampling was performed from March to September 2014. We employed the Larson's Sexual Satisfaction Questionnaire for gathering the data. Data were analyzed using descriptive statistics and Chi-square, t-test and linear regression analysis. The means of sexual satisfaction in patients exposure with ischemic heart disease and among the subjects without exposure it were 101.47±13.42 and 100.91±16.52, respectively. There was no significant difference between the two groups regarding sexual satisfaction. However, sexual satisfaction was significantly correlated with gender and the use of cardiac medications (P valuepay closer attention to patient education about sexual issues.

  4. Visible aging signs as risk markers for ischemic heart disease

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2016-01-01

    Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from...

  5. Rapid determination of the hypoxanthine increase in ischemic exercise tests

    NARCIS (Netherlands)

    Bolhuis, P. A.; Zwart, R.; Bär, P. R.; de Visser, M.; van der Helm, H. J.

    1988-01-01

    After ischemic exercise tests, performed to detect glycogenoses or myoadenylate deaminase (EC 3.5.4.6) deficiency, the increases in serum lactate and ammonia usually are measured. Determination of hypoxanthine instead of ammonia can also be used to show myoadenylate deaminase deficiency, but HPLC of

  6. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic ...

    African Journals Online (AJOL)

    Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 ...

  7. Causes and Treatment of Acute Ischemic Stroke During Pregnancy.

    Science.gov (United States)

    Terón, Ina; Eng, Melissa S; Katz, Jeffrey M

    2018-05-21

    Treatment recommendations for pregnancy associated ischemic stroke are scarce. This may be due to the fact that, in general, obstetricians tend not to make recommendations for stroke patients and neurologists are not commonly involved in the care of pregnant women. Herein, we review the multiple etiologies of ischemic stroke during pregnancy, considerations for diagnostic testing, and acute treatment and prevention options, including associated risks specific to the pregnant and puerperal state. Intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy have been used successfully to treat pregnant women with acute ischemic stroke. Recent national guidelines recommend considering tPA use during pregnancy for moderate and severe strokes if the potential benefits offset the risks of uterine hemorrhage. Pregnancy-associated ischemic stroke is rare, but can be devastating, and recanalization therapy should not be systematically withheld. Women who are at risk for stroke should be followed carefully, and providers caring for pregnant women should be educated regarding stroke signs and symptoms. Many of the standard post stroke diagnostic modalities may be used safely in pregnancy, and primary and secondary stroke prevention therapy must be tailored to avoid fetal toxicity.

  8. Indigenous drugs in ischemic heart disease in patients with diabetes.

    Science.gov (United States)

    Dwivedi, Shridhar; Aggarwal, Amitesh

    2009-11-01

    India is currently facing the silent epidemic of ischemic heart disease, type 2 diabetes mellitus (T2DM), hypertension, and stroke. Both diabetes and ischemic heart disease appear in Indian people a decade earlier compared to whites. The recent evidence that certain medicinal plants possess hypoglycemic, lipid-lowering, and immunomodulating properties on account of their rich flavonoid and/or other glucose-lowering active constituents merits scientific scrutiny in this regard. The present communication aims to give a brief review of those plants that could be useful in T2DM associated with hypertension, ischemic heart disease, and/or dyslipidemia. Aegle marmelos (bael), Allium sativum (garlic), Curcuma domestica (turmeric), Eugenia jambolana (jamun), Murraya koenigii (curry leaves), Trigonella foenum graecum (fenugreek), and Terminalia arjuna (arjun) have been found to be useful in diabetes associated with ischemic heart disease. Their active biomolecules have been identified. They have also been demonstrated to be safe in long-term use. Further clinical research regarding their potency and efficacy vis-à-vis oral hypoglycemics needs to done.

  9. Acute ischemic stroke and long-term outcome after thrombolysis

    DEFF Research Database (Denmark)

    Schmitz, Marie Louise; Simonsen, Claus Z; Hundborg, Heidi

    2014-01-01

    to compute adjusted hazard ratios for all outcomes. RESULTS: Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score-matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long...

  10. Treatment and partial recovery of ischemic stroke hemiplegy through acupuncture

    Directory of Open Access Journals (Sweden)

    David Gonçalves Nordon

    2011-06-01

    Full Text Available ABSTRACT We present the case of a patient with hemiplegy and dysphonia due to an ischemic stroke in the pons who was treated through classical systemic and scalpean acupuncture and electroacupuncture, presenting considerable improvement in speaking, walking and moving her right arm after three months of treatment.

  11. Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke

    DEFF Research Database (Denmark)

    Ölmestig, Joakim N E; Marlet, Ida R; Hainsworth, Atticus H

    2017-01-01

    Phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil (Viagra®) are widely used for erectile dysfunction and pulmonary hypertension. Preclinical studies suggest that PDE5i may improve functional outcome following ischemic stroke. In this systematic review we aimed to evaluate the effects...

  12. The risk of ischemic optic neuropathy post phacoemulsification cataract surgery.

    Science.gov (United States)

    Al-Madani, Mousa Victor; Al-Raqqad, Nancy Khalaf; Al-Fgarra, Naser Abdallah; Al-Thawaby, Amal Mousa; Jaafar, Ahmed Abdelra'of

    2017-01-01

    The aim was to study the risk of non arteritic ischemic optic neuropathy after phacoemulsification cataract surgery. This study was conducted at King Hussein Medical Center during the period between January 2015 and July 2016. Patients attending ophthalmology clinic complaining of decreased vision due to lens opacity were evaluated. Patients were divided into two groups. First group included patients with no medical illness and second group included patients with diabetes mellitus, hypertension or hyperlipidemia. The two groups were further divided into two subgroups. First subgroup included patients who had phacoemulsification surgery and second subgroup did not have surgery. All patients were followed up for 6 months. They were assessed by neuro-ophthalmologist looking for ischemic optic neuropathy. A total number of 568 patients were enrolled. Group 1A included patients with no medical illness who underwent surgery and group 1B did not undergo surgery. The number of patients in these two subgroups was 119 and 103 respectively. Number of patients in group 2A (medical illness and surgery) was 188 and number of patients in group 2B (medical illness and no surgery) was 130. The incidence of ischemic optic neuropathy was 4.3 % in group 2A, 4.2 % in group 1A, 0.8% in group 2B, and 0% in group 1B. Phacoemulsification is a risk factor for non arteritic ischemic optic neuropathy independent of the presence of medical risk factors. Suggested mechanisms would be local anaesthesia, intraocular pressure fluctuation and local intraocular inflammation.

  13. Obesity increases risk of ischemic stroke in young adults.

    Science.gov (United States)

    Mitchell, Andrew B; Cole, John W; McArdle, Patrick F; Cheng, Yu-Ching; Ryan, Kathleen A; Sparks, Mary J; Mitchell, Braxton D; Kittner, Steven J

    2015-06-01

    Body mass index has been associated with ischemic stroke in older populations, but its association with stroke in younger populations is not known. In light of the current obesity epidemic in the United States, the potential impact of obesity on stroke risk in young adults deserves attention. A population-based case-control study design with 1201 cases and 1154 controls was used to investigate the relationship of obesity and young onset ischemic stroke. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between body mass index and ischemic stroke with and without adjustment for comorbid conditions associated with stroke. In analyses adjusted for age, sex, and ethnicity, obesity (body mass index >30 kg/m(2)) was associated with an increased stroke risk (odds ratio, 1.57; 95% confidence interval, 1.28-1.94) although this increased risk was highly attenuated and not statistically significant after adjustment for smoking, hypertension, and diabetes mellitus. These results indicate that obesity is a risk factor for young onset ischemic stroke and suggest that this association may be partially mediated through hypertension, diabetes mellitus, or other variables associated with these conditions. © 2015 American Heart Association, Inc.

  14. Urinary and plasma magnesium and risk of ischemic heart disease

    NARCIS (Netherlands)

    Joosten, Michel M.; Gansevoort, Ron T.; Mukamal, Kenneth J.; van der Harst, Pim; Geleijnse, Johanna M.; Feskens, Edith J. M.; Navis, Gerjan; Bakker, Stephan J. L.

    Background: Previous studies on dietary magnesium and risk of ischemic heart disease (IHD) have yielded inconsistent results, in part because of a lack of direct measures of actual magnesium uptake. Urinary excretion of magnesium, an indicator of dietary magnesium uptake, might provide more

  15. Ischemic Colitis of the Left Colon in a Diabetic Patient

    Directory of Open Access Journals (Sweden)

    Anastasios J. Karayiannakis

    2011-04-01

    Full Text Available Diabetes mellitus may affect the gastrointestinal tract possibly as a result of autonomic neuropathy. Here we present a 68-year-old male with non-insulin-dependent diabetes mellitus who presented with prolonged watery diarrhea and in whom imaging studies demonstrated ischemic colitis of the left colon. Resection of the affected colon resulted in sustained disappearance of symptoms.

  16. Application of mechanical embolectomy in acute ischemic stroke

    International Nuclear Information System (INIS)

    Lu Haitao; Li Minghua; Zhao Jungong

    2008-01-01

    Acute ischemic stroke is a common disease serevely threatening the public health. The main management involves intravenous thrombolysis, intra-arterial thrombolysis and mechanical embolectomy. Recently, endovascular mechanical embolectomy is attracted more attention because it provides a good outcome for patients either ineligible not responsible for IV thrombolytic therapy. The article reviews the relative aspects with summerization in this field. (authors)

  17. Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).

    Science.gov (United States)

    Brown, Arleen F; Liang, Li-Jung; Vassar, Stefanie D; Stein-Merkin, Sharon; Longstreth, W T; Ovbiagele, Bruce; Yan, Tingjian; Escarce, José J

    2011-12-01

    Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

  18. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

    African Journals Online (AJOL)

    The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

  19. Hereditary hemochromatosis and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer

    2005-01-01

    BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...

  20. Parvovirus B19 Infection in Children With Arterial Ischemic Stroke.

    Science.gov (United States)

    Fullerton, Heather J; Luna, Jorge M; Wintermark, Max; Hills, Nancy K; Tokarz, Rafal; Li, Ying; Glaser, Carol; DeVeber, Gabrielle A; Lipkin, W Ian; Elkind, Mitchell S V

    2017-10-01

    Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases. The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens. Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries. Using MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis. © 2017 American Heart Association, Inc.

  1. Intravenous Thrombolysis in Acute Ischemic Stroke with Active Cancer

    Directory of Open Access Journals (Sweden)

    Ki-Woong Nam

    2017-01-01

    Full Text Available Ischemic stroke patients with active cancer are known to have poor clinical outcomes. However, the efficacy and safety of intravenous alteplase (IV t-PA in this group are still unclear. In this study, we aimed to evaluate whether stroke patients with cancer had poor clinical outcomes after use of IV t-PA. We reviewed ischemic stroke patients with active cancer treated with isolated IV t-PA between April 2010 and March 2015 at three national university hospitals from the registry for ischemic stroke in Korea. The clinical outcomes of early neurological deterioration (END, hemorrhagic transformation, in-hospital mortality, 3-month modified Rankin scale (mRS, the National Institutes of Health Stroke Scale (NIHSS discharge score, and duration of hospitalization were compared. We enrolled a total of 12 patients, and the cohort showed poor outcomes including 4 (33% END events, 7 (58% hemorrhagic transformations, 3 (25% in-hospital mortality cases, and 7 (58% poor mRS (3–6 scores. Additionally, the cryptogenic stroke group (n = 6 more frequently had high mRS scores (P = 0.043 as well as tendencies for frequent END events, hemorrhagic transformations, in-hospital mortality cases, and higher discharge NIHSS scores without statistical significance. In conclusion, ischemic stroke patients with active cancer, especially those with a cryptogenic mechanism, showed poor clinical outcomes after use of IV t-PA.

  2. Newer concepts in the pathophysiology of ischemic heart disease.

    Science.gov (United States)

    Kirk, E S; Factor, S; Sonnenblick, E H

    1984-11-01

    Thus the thrust of these studies suggests that blood flow is the overwhelming factor in determining the consequences of the imbalance of oxygen supply and demand. Moreover, the factors that determine the requirements for tissue survival in the presence of deep ischemia are not the same as those shown for the normal myocardium in figure 1. In deep ischemia, contraction ceases, and metabolism shifts from aerobic to anaerobic pathways. Survival rather than contractile function then becomes the agenda. Not only does supply tend to overshadow demand in determining extent of transmural necrosis, but the anatomical pattern of supply precisely delineates the region at risk following a coronary occlusion as well as the ultimate extent of infarction. These views are summarized in the model presented in figures 12 and 13. The anatomic distribution of the ligated artery determines the lateral limits of the ischemic region (Fig. 12) and thus the lateral extension of necrosis (Fig. 13). The extension of the necrosis across the heart wall depends largely on the status of perfusion within the ischemic region. Extension of an infarct, should it occur, has to be explained by other mechanisms. These might include: (i) vascular obstruction in adjacent vascular systems that were not involved in the first occlusion, (ii) relative ischemia in the normal tissue surrounding the ischemic tissue due to an increased wall stress at the demarcation between contracting and noncontracting tissue, or (9) interruption of vessels supplying large interdigitations of normal tissue within the originally ischemic tissue due to changes associated with the process of infarction of ischemia. Alternatively, much that is called extension of infarction may involve more of the wall transmurally without lateral extension. Additional features of the development of myocardial infarction in figures 12 and 13 include: (i) the development of collateral vessel function resulting in an increased capacity to supply the

  3. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    Science.gov (United States)

    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  4. Usefulness of perfusion MR imaging in hyperacute ischemic stroke

    International Nuclear Information System (INIS)

    Park, Ji Hoon; Kim, Jae Hyoung; Shin, Tae Min; Lee, Eun Ja; Chung, Sung Hoon; Choi, Nack Cheon; Lim, Byeong Hoon; Kim, In One

    1998-01-01

    Perfusion MR imaging is a new technique for the assessment of acute ischemic stroke. The aim of this study was to evaluate the usefulness of this imaging in hyperacute ischemic stroke in comparison with conventional CT and MR imaging. Eight patients presenting the symptoms of acute ischemic stroke due to middle cerebral artery occlusion were included in this study. Within 2 hours of initial CT scan and 6 hours after the onset of stroke, perfusion MR imaging was performed in all patients using a single-section dynamic contrast-enhanced T2*-weighted imager in conjunction with conventional routine MR imaging and MR angiography. Cerebral blood volume (CBV) maps were then obtained from dynamic MR imaging data by using numerical integration techniques. The findings of CBV maps were compared with those of initial and follow-up CT or MR images. The findings of CBV maps were obviously abnormal in all patients, as compared with normal or focal subtle abnormal findings seen on initial CT and MR images. CBV in the occluded arterial territory was lower in all eight patients;two had focal regions of increased CBV within the affected territory, indicating reperfusion hyperemia. In all patients, regions of abnormal CBV were eventually converted to infarctions on follow-up images. Perfusion MR imaging was useful for the evaluation of hemodynamic change occurring during cerebral perfusion in hyperacute ischemic stroke, and prediction of the final extent of infarction. These results suggest that pertusion MR imaging can play an important role in the diagnosis and management of hyperacute ischemic stroke.=20

  5. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    International Nuclear Information System (INIS)

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-01-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35–54 had a 1.66 times (95% CI, 1.16–2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55–64 years (hazard ratio = 0.87; 95% CI, 0.56–1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  6. Enterocolic lymphocytic phlebitis: statistical analysis of histology features in viable and ischemic bowel.

    Science.gov (United States)

    Medlicott, Shaun A C; Guggisberg, Kelly A; DesCôteaux, Jean-Gaston; Beck, Paul

    2006-07-01

    Enterocolic lymphocytic phlebitis is a rare cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Myointimal hyperplasia may represent a chronic phase of enterocolic lymphocytic phlebitis. Subclinical or early stage enterocolic lymphocytic phlebitis is not well delineated. We analyzed 600 submucosal and subserosal veins from both ischemic and intact bowel segments to discern if vascular morphology varied between sites. Crescentic and circumferential lymphocytic phlebitis is more common in viable bowel than in the ischemic segment. A nonsignificant trend was found for increased crescentic morphology between intact bowel remote from the ischemic focus compared with that adjacent to the ischemic focus. Hallmarks of ischemic bowel are necrotizing phlebitis and thrombi formation. Thrombophlebitis morphology is distinctly different in viable and ischemic bowel, changing from the classic lymphocytic to necrotizing lesions respectively.

  7. Cardiorespiratory Fitness after Transient Ischemic Attack and Minor Ischemic Stroke : Baseline Data of the MoveIT Study

    NARCIS (Netherlands)

    Boss, H. Myrthe; Deijle, Inger A.; Van Schaik, Sander M.; de Melker, Edwin C.; van den Berg, Bob T.J.; Weinstein, Henry C.; Geerlings, Mirjam I.; Kappelle, L. Jaap; Van den Berg-Vos, Renske M.

    2017-01-01

    Background Cardiorespiratory fitness (CRF) is reduced in patients with stroke. It is unclear whether it is also reduced in patients with a transient ischemic attack (TIA) or minor stroke. We investigated the CRF in patients with a recent TIA or minor stroke and explored which determinants are

  8. Transient Ischemic Attack and Ischemic Stroke in Danon Disease with Formation of Left Ventricular Apical Thrombus despite Normal Systolic Function

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-01-01

    Full Text Available Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder presenting with hypertrophic cardiomyopathy, Wolf-Parkinson-White syndrome, skeletal myopathy, and mild intellectual disability. Early morbidity and mortality due to heart failure or sudden death are known in Danon disease, more in males than in females. Here, we present a 17-year-old female adolescent with Danon disease and severe concentric hypertrophy with normal left ventricular (LV systolic function, who has been complaining of intermittent headache and weakness for about 3 years, initially diagnosed with hemiplegic migraine. Subsequently, her neurological manifestation progressed to transient ischemic attack (TIA and eventually to ischemic stroke confirmed by CT scan with 1-day history of expressive aphasia followed by persistent left side weakness and numbness. Detailed echocardiogram for the first time revealed a small LV apical thrombus with unchanged severe biventricular hypertrophy and normal systolic function. This unexpected LV apical thrombus may be associated with a wide spectrum of neurological deficits ranging from TIA to ischemic stroke in Danon disease. Possibility of cerebral ischemic events should be suspected in Danon disease when presenting with neurological deficits even with normal systolic function. Careful assessment for LV apical thrombus is warranted in such cases.

  9. Physical protection

    International Nuclear Information System (INIS)

    Myers, D.A.

    1989-01-01

    Physical protection is defined and its function in relation to other functions of a State System of Accounting for and Control of Nuclear Materials is described. The need for a uniform minimum international standard for physical protection as well as the need for international cooperation in physical protection is emphasized. The IAEA's INFCIRC/225/Rev. 1 (Annex 1) is reviewed. The Convention on the Physical Protection of Nuclear Material (Annex 2) is discussed. Photographs show examples of typical physical protection technology (Annex 3)

  10. Diplomatic Protection

    OpenAIRE

    Režná, Jana

    2006-01-01

    Final thesis Topic: Diplomatic protection Thesis supervisor: JUDr. Vladimír Balaš, CSc. Student: Marek Čermák Thesis on the topic of diplomatic protection deals with the granting of exercise of diplomatic protection by the states and is divided into seven chapters which follow each other. The first chapter describes the diplomatic protection and its historical foundations. The second chapter focuses on the possibility of exercise of diplomatic protection in respect of natural persons and the ...

  11. Remote pre-procedural ischemic stroke as the greatest risk in carotid‑stenting‑associated stroke and death: a single center's experience.

    Science.gov (United States)

    Rašiová, Mária; Špak, Ľubomír; Farkašová, Ľudmila; Pataky, Štefan; Koščo, Martin; Hudák, Marek; Moščovič, Matej; Leško, Norbert

    2017-08-01

    The goal of carotid artery stenting (CAS) is to decrease the stroke risk in patients with carotid stenosis. This procedure carries an immediate risk of stroke and death and many patients do not benefit from it, especially asymptomatic patients. It is crucial to accurately select the patients who would benefit from carotid procedure, and to rule out those for whom the procedure might be hazardous. Remote ischemic stroke is a known risk factor for stroke recurrence during surgery. The aim of our study was to determine the periprocedural complication risk (within 30 days after CAS) associated with carotid stenting (stroke, death) in patients with and without remote pre-procedural ischemic stroke, to analyze periprocedural risk in other specific patient subgroups treated with CAS, and to determine the impact of observed variables on all-cause mortality during long-term follow-up. We conducted a retrospective review of prospectively collected data from all patients treated with protected CAS between June 20, 2008 and December 31, 2015. Patient age, gender, type of carotid stenosis (symptomatic versus asymptomatic), side of stenosis (right or left carotid artery), type of cerebral protection (proximal versus distal), presence of comorbidities (remote ischemic pre-procedural ischemic stroke, coronary artery disease, diabetes mellitus, peripheral artery disease), previous ipsilateral carotid endarterectomy (CEA), contralateral carotid occlusion (CCO) and previous contralateral CAS/CEA were analyzed to identify higher CAS risk and to determine the impact of these variables on all-cause mortality during follow-up. Survival data were obtained from the Health Care Surveillance Authority registry. Mean follow-up was 1054 days (interquartile range 547.3; 1454.8). Remote pre-procedural ischemic stroke was defined as any-territory ischemic stroke >6 months prior to CAS. Primary periprocedural endpoint incidence (stroke/death) in 502 patients was 3.8% (N.=19) of all patients, 5

  12. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available Th