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Sample records for ischemic mice receiving

  1. Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

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    Xiao-Hui Dong

    2017-10-01

    Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

  2. Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice.

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    Wei, Zheng Zachory; Zhang, James Ya; Taylor, Tammi M; Gu, Xiaohuan; Zhao, Yingying; Wei, Ling

    2018-03-01

    Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

  3. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

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    Yu Ri Kim

    2017-02-01

    Full Text Available The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ augmentation for cilostazol (CLS-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS. Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.

  4. 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

  5. How study patients who receive fluo pyrimidines to prevent ischemic events

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    Saldombide, L.

    2010-01-01

    Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed

  6. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

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    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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    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.

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

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    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.

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

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    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.

  10. Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.

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    Jamie K Wong

    Full Text Available Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP signaling, results in neuroprotection in an ischemia-reperfusion (I/R stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1(-/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO, Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy.

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

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    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.

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

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    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.

  13. Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

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    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. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

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    Easton, J Donald; Aunes, Maria; Albers, Gregory W; Amarenco, Pierre; Bokelund-Singh, Sara; Denison, Hans; Evans, Scott R; Held, Peter; Jahreskog, Marianne; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

    2017-09-05

    Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2

  15. Annexin V Imaging Detects Diabetes-Accelerated Apoptosis and Monitors the Efficacy of Benfotiamine Treatment in Ischemic Limbs of Mice

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    Kyung-Ho Jung

    2014-05-01

    Full Text Available The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

  16. Annexin V imaging detects diabetes-accelerated apoptosis and monitors the efficacy of benfotiamine treatment in ischemic limbs of mice.

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    Jung, Kyung-Ho; Lee, Jin Hee; Park, Jin Won; Paik, Jin Young; Quach, Cung Hoa Thien; Lee, Eun Jeong; Lee, Kyung-Han

    2014-01-01

    The role of apoptosis imaging for monitoring treatment response in ischemic limbs has not been properly explored. In this study, we investigated the ability of annexin V (AnxV) imaging to assess the efficacy of antiapoptotic treatment in ischemic limbs of diabetic mice. Normal C57BL/6 mice and streptozotocin-induced diabetic mice were subject to hindlimb ischemia. AnxV-conjugated fluorescent streptavidin probes were intravenously injected, and optical imaging was performed. Tissue apoptosis was quantified by histochemistry and Western blotting. The AnxV probes showed specific targeting to apoptotic cells on confocal microscopy and flow cytometry. Intravenous AnxV probes displayed substantially greater accumulation in ischemic limbs of diabetic mice. Benfotiamine (BFT) treatment of diabetic mice led to better perfusion recovery on laser Doppler imaging and reduced AnxV binding on optical imaging. TUNEL staining and cleaved caspase-3 Western blots confirmed accelerated apoptosis by diabetes and its suppression by BFT treatment. Furthermore, AnxV-SAv-PEcy5.5 uptake in the ischemic limbs closely correlated to cleaved caspase-3 expression. Thus, AnxV imaging may be useful for monitoring the efficacy of therapeutic agents designed to suppress ischemia-induced apoptosis.

  17. A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil

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    Felekis T

    2011-10-01

    Full Text Available T Felekis1, I Asproudis1, K Katsanos2, EV Tsianos21University Eye Clinic of Ioannina, Ioannina, Greece; 2First Department of Internal Medicine, University Hospital of Ioannina, Ioannina, GreeceAbstract: A 51-year-old male was referred to the University Eye Clinic of Ioannina with nonarteritic anterior ischemic optic neuropathy (NAION 12 hours after receiving sildenafil citrate (Viagra®. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral NAION. Although a cause-and-effect relationship is difficult to prove, there are reports indicating an association between the use of erectile dysfunction agents and the development of NAION. Physicians might need to investigate the presence of family history of NAION among systemic or vascular predisposing risk factors before prescribing erectile dysfunction drugs.Keywords: sildenafil, nonarteritic anterior ischemic optic neuropathy, erectile dysfunction drugs, family history

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

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    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.

  19. DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

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    Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

    2017-01-01

    The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

  20. Race/Ethnic differences in the risk of hemorrhagic complications among patients with ischemic stroke receiving thrombolytic therapy.

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    Mehta, Rajendra H; Cox, Margueritte; Smith, Eric E; Xian, Ying; Bhatt, Deepak L; Fonarow, Gregg C; Peterson, Eric D

    2014-08-01

    Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke. Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke. Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04-1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications. In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy. © 2014 American Heart Association, Inc.

  1. Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice.

    Science.gov (United States)

    Mohammed, Nagat; Ceprian, Maria; Jimenez, Laura; Pazos, M Ruth; Martínez-Orgado, Jose

    2017-01-01

    A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation). CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction. CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

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    Andrea Leiva

    Full Text Available For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI, a high-density lipoprotein (HDL receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the

  3. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

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    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  4. Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Nirmal

    2007-01-01

    The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysfunction in mice. Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in mice. Short-term memory was evaluated using the elevated plus maze test. The inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced impaired short-term memory, motor co-ordination and lateral push response. Three episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced behavioral deficit measured in terms of loss of short-term memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that beneficial effects of ischemic postconditioning on global cerebral ischemia and reperfusion-induced behavioral deficits may involve activation of phosphoinositide 3-kinase-linked pathway.

  5. Evidence for the role of histaminergic pathways in neuroprotective mechanism of ischemic postconditioning in mice.

    Science.gov (United States)

    Kaur, Indresh; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal

    2017-08-01

    The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning (iPoCo). Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce I/R-induced cerebral injury in National Institutes of Health mice mice. iPoCo involving three episodes of carotid artery occlusion and reperfusion of 10 sec each was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water maze test. Rotarod test, inclined beam-walking test, and neurological severity score (NSS) were performed to assess motor incoordination and sensorimotor abilities. Brain acetylcholine esterase (AChE) activity, brain myeloperoxidase (MPO) activity, brain thiobarbituric acid-reactive species (TBARS), and glutathione level (GSH) were also estimated. BCAO produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑AChE, ↑MPO ↓GSH, and ↑TBARS). iPoCo attenuated the deleterious effect of BCAO on infarct size, memory, NSS, motor coordination, and biochemical markers. Pretreatment of carnosine (a histamine [HA] precursor) potentiated the neuroprotective effects of iPoCo, whereas pretreatment of ketotifen (HA H1 receptor blocker and mast cell stabilizer) abolished the protective effects of iPoCo as well as that of carnosine on iPoCo. It may be concluded that neuroprotective effect of iPoCo probably involves activation of histaminergic pathways. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  6. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

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    Li-Li Wang

    Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

  7. Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

    Directory of Open Access Journals (Sweden)

    Hori Motohide

    2012-11-01

    and protein targets in mice ischemic brain, and suggests new targets for thereaupetic interventions.

  8. Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

    Science.gov (United States)

    Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

    2017-12-01

    Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart

  9. How study patients who receive fluo pyrimidines to prevent ischemic events; Como estudiar los pacientes que recibiran fluopirimidinas para prevenir eventos isquemicos

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    Saldombide, L. [Hospital de Clinicas. Montevideo (Uruguay)

    2010-11-15

    Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed.

  10. Ischemic preconditioning protects against ischemic brain injury

    Directory of Open Access Journals (Sweden)

    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.

  11. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

  12. Basal ganglia perfusion using dynamic color Doppler sonography in infants with hypoxic ischemic encephalopathy receiving therapeutic hypothermia: a pilot study.

    Science.gov (United States)

    Faingold, Ricardo; Cassia, Guilherme; Morneault, Linda; Saint-Martin, Christine; Sant'Anna, Guilherme

    2016-10-01

    The objective of this study was to evaluate the cerebral perfusion of the basal ganglia in infants with hypoxic-ischemic encephalopathy (HIE) receiving hypothermia using dynamic color Doppler sonography (CDS) and investigate for any correlation between these measurements and survival. Head ultrasound (HUS) was performed with a 9S4 MHz sector transducer in HIE infants submitted to hypothermia as part of their routine care. Measurements of cerebral perfusion intensity (CPI) with an 11LW4 MHz linear array transducer were performed to obtain static images and DICOM color Doppler videos of the blood flow in the basal ganglia area. Clinical and radiological data were evaluated retrospectively. The video images were analyzed by two radiologists using dedicated software, which allows automatic quantification of color Doppler data from a region of interest (ROI) by dynamically assessing color pixels and flow velocity during the heart cycle. CPI is expressed in cm/sec and is calculated by multiplying the mean velocity of all pixels divided by the area of the ROI. Three videos of 3 seconds each were obtained of the ROI, in the coronal plane, and used to calculate the CPI. Data are presented as mean ± SEM or median (quartiles). A total of 28 infants were included in this study: 16 male, 12 female. HUS was performed within the first 48 hours of therapeutic hypothermia treatment. CPI values were significantly higher in the seven non-survivors when compared to survivors (0.226±0.221 vs . 0.111±0.082 cm/sec; P=0.02). Increased perfusion intensity of the basal ganglia area within the first 48 of therapeutic hypothermia treatment was associated with poor outcome in neonates with HIE.

  13. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    Science.gov (United States)

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.

  14. Neurological outcomes in patients with ischemic stroke receiving enoxaparin or heparin for venous thromboembolism prophylaxis: subanalysis of the Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study.

    Science.gov (United States)

    Kase, Carlos S; Albers, Gregory W; Bladin, Christopher; Fieschi, Cesare; Gabbai, Alberto A; O'Riordan, William; Pineo, Graham F

    2009-11-01

    The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression. Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage. Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression. The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared

  15. A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

    Directory of Open Access Journals (Sweden)

    Faikah Gueler

    Full Text Available Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx. In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV, might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days was initiated 24 hours after IRI when acute kidney injury (AKI was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF and glomerular filtration rate (GFR at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

  16. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

    Directory of Open Access Journals (Sweden)

    Hong-Jhang Chen

    Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

  17. Hypoglossal motoneurons in newborn mice receive respiratory drive from both sides of the medulla

    DEFF Research Database (Denmark)

    Tarras-Wahlberg, S; Rekling, J C

    2009-01-01

    Respiratory motor output in bilateral cranial nerves is synchronized, but the underlying synchronizing mechanisms are not clear. We used an in vitro slice preparation from newborn mice to investigate the effect of systematic transsections on respiratory activity in bilateral XII nerves. Complete...... in bilateral XII nerves. Hypoglossal motoneurons receive respiratory drive from both sides of the medulla, possibly mediated by contralaterally projecting dendrites....

  18. Ischemic postconditioning confers cardioprotection and prevents reduction of Trx-1 in young mice, but not in middle-aged and old mice.

    Science.gov (United States)

    Perez, Virginia; D Annunzio, Verónica; Mazo, Tamara; Marchini, Timoteo; Caceres, Lourdes; Evelson, Pablo; Gelpi, Ricardo J

    2016-04-01

    Thioredoxin-1 (Trx-1) is part of an antioxidant system that maintains the cell redox homeostasis but their role on ischemic postconditioning (PostC) is unknown. The aim of this work was to determine whether Trx-1 participates in the cardioprotective mechanism of PostC in young, middle-aged, and old mice. Male FVB young (Y: 3 month-old), middle-aged (MA: 12 month-old), and old (O: 20 month-old) mice were used. Langendorff-perfused hearts were subjected to 30 min of ischemia and 120 min of reperfusion (I/R group). After ischemia, we performed 6 cycles of R/I (10 s each) followed by 120 min of reperfusion (PostC group). We measured the infarct size (triphenyltetrazolium); Trx-1, total and phosphorylated Akt, and GSK3β expression (Western blot); and the GSH/GSSG ratio (HPLC). PostC reduced the infarct size in young mice (I/R-Y: 52.3 ± 2.4 vs. PostC-Y: 40.0 ± 1.9, p Trx-1 expression decreased after I/R, and the PostC prevented the protein degradation in young animals (I/R-Y: 1.05 ± 0.1 vs. PostC-Y: 0.52 ± .0.07, p Trx-1 degradation, decreasing oxidative stress and allowing the activation of Akt and GSK3β to exert its cardioprotective effect. This protection mechanism is not activated in middle-aged and old animals.

  19. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

    Science.gov (United States)

    Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

    2016-02-15

    Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

  20. Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Zhang

    2018-01-01

    Full Text Available Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.

  1. Possible role of pannexin 1/P2x7 purinoceptor in neuroprotective mechanism of ischemic postconditioning in mice.

    Science.gov (United States)

    Mahi, Namarta; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal; Dhawan, Ravi

    2015-06-01

    Previous studies have suggested a significant role of pannexin 1 (Panx1)/P2X7 receptor complex in cardioprotective mechanism of ischemic preconditioning and postconditioning (IPC). The present study has been undertaken to investigate whether Panx1/P2X7 purinoceptors are also involved in the neuroprotective mechanism of IPC in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce ischemia-reperfusion-induced cerebral injury in Swiss albino mice. For IPC immediately after BCAO of 12 min, three cycles of 10-s ischemia and reperfusion each were given and then prolonged reperfusion of 24 h was used. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam walking test, and neurologic severity score (NSS) were used to assess motor dysfunction. Acetylcholine esterase levels, brain thiobarbituric acid reactive species, and glutathione level were also estimated. BCAO followed by reperfusion produced a significant increase in cerebral infarct size, NSS along with impairment of memory and motor dysfunction. It also increased brain acetylcholine esterase, thiobarbituric acid reactive species levels, and decreased the glutathione level. IPC produced a significant decrease in the cerebral infarct size and NSS along with reversal of ischemia-reperfusion-induced impairment of memory, motor dysfunction, and altered biochemical levels in the brain. IPC-induced neuroprotective effects were significantly abolished by pretreatment of mefloquine (15.0 mg/kg orally; 30.0 mg/kg orally), blocker of Panx1/P2X7 purinoceptor. Therefore, activation of Panx1/P2X7 purinoceptors appears to play a significant role in the neuroprotective mechanism of IPC. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Tadalafil enhances the neuroprotective effects of ischemic postconditioning in mice, probably in a nitric oxide associated manner.

    Science.gov (United States)

    Gulati, Puja; Singh, Nirmal

    2014-05-01

    This study investigates the modulatory effect of tadalafil, a selective phosphodiesterase (PDE-5) inhibitor, on the neuroprotective effects of ischemic postconditioning (iPoCo) in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion induced cerebral injury. Cerebral infarct size was measured using TTC staining. Memory was assessed using the Morris water maze test. Degree of motor incoordination was evaluated using inclined beam-walking, rota-rod, and lateral push tests. Brain nitrite/nitrate, acetylcholinesterase activity, TBARS, and glutathione levels were also estimated. BCAO followed by reperfusion produced a significant increase in cerebral infarct size, brain nitrite/nitrate and TBARS levels, and acetylcholinesterase activity along with a reduction in glutathione. Marked impairment of memory and motor coordination was also noted. iPoCo consisting of 3 episodes of 10 s carotid artery occlusion and reperfusion instituted immediately after BCAO significantly decreased infarct size, memory impairment, motor incoordination, and altered biochemistry. Pretreatment with tadalafil mimicked the neuroprotective effects of iPoCo. The tadalafil-induced neuroprotective effects were significantly attenuated by l-NAME, a nonselective NOS inhibitor. We concluded that tadalafil mimics the neuroprotective effects of iPoCo, probably through a nitric oxide dependent pathway, and PDE-5 could be a target of interest with respect to the neuroprotective mechanism of iPoCo.

  3. BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

    Science.gov (United States)

    McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D

    2017-07-18

    Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1 , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6- Lsq1-3 ). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3 Ile81 , but not BAG3 Met81 , improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3 Ile81 (n=9), but not BAG3 Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3 Met81 , BAG3 Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle

  4. Vector-free and transgene-free human iPS cells differentiate into functional neurons and enhance functional recovery after ischemic stroke in mice.

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    Osama Mohamad

    Full Text Available Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice.

  5. 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.

  6. XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.

    Science.gov (United States)

    Jiang, Meng; Yu, Shu; Yu, Zhui; Sheng, Huaxin; Li, Ying; Liu, Shuai; Warner, David S; Paschen, Wulf; Yang, Wei

    2017-06-01

    Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke. Mice with Xbp1 loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation. Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice. Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains. © 2017 American Heart Association, Inc.

  7. Synergism and rules from combination of Baicalin, Jasminoidin and Desoxycholic acid in refined Qing Kai Ling for treat ischemic stroke mice model.

    Directory of Open Access Journals (Sweden)

    Jian Li

    Full Text Available Refined Qing-Kai-Ling (QKL, a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid, plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA and principal component analysis (PCA to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5 could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4 were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM, emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.

  8. Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

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    Peter Kraft

    2010-12-01

    Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

  9. Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2+/- mice

    NARCIS (Netherlands)

    Hoekstra, H; Porte, RJ; Tian, Y; Jochum, W; Stieger, B; Moritz, W; Slooff, MJH; Graf, R; Clavien, PA

    Intrahepatic bile duct strictures are a serious complication after orthotopic liver transplantation (OLT). We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type mice and mice heterozygous for disruption of the multidrug

  10. Investigation of the role of non-selective calcium channel blocker (flunarizine) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice.

    Science.gov (United States)

    Gulati, Puja; Muthuraman, Arunachalam; Kaur, Parneet

    2015-04-01

    The present study was designed to investigate the role of flunarizine (a non-selective calcium channel blocker) on cerebral ischemic-reperfusion associated cognitive dysfunction in aged mice. Bilateral carotid artery occlusion of 12min followed by reperfusion for 24h was given to induce cerebral injury in male Swiss mice. The assessment of learning & memory was performed by Morris water maze test; motor in-coordination was evaluated by rota rod, lateral push and inclined beam walking tests; cerebral infarct size was quantified by triphenyltetrazolium chloride staining. In addition, reduced glutathione (GSH), total calcium and acetylcholinesterase (AChE) activity were also estimated in aged brain tissue. Donepezil treated group served as a positive control in this study. Ischemia reperfusion (I/R) injury produced significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Further, I/R injury also produced significant increase in levels of total calcium, AChE activity and decrease in GSH levels. Pretreatment of flunarizine significantly attenuated I/R induced infarct size, behavioral and biochemical changes. Hence, it may be concluded that, a non-selective calcium channel blocker can be useful in I/R associated cognitive dysfunction due to its anti-oxidant, anti-infarct and modulatory actions of neurotransmitters & calcium channels. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Reduced blood brain barrier breakdown in P-selectin deficient mice following transient ischemic stroke: a future therapeutic target for treatment of stroke

    Directory of Open Access Journals (Sweden)

    Petterson Jodie

    2010-02-01

    Full Text Available Abstract Background The link between early blood- brain barrier (BBB breakdown and endothelial cell activation in acute stroke remain poorly defined. We hypothesized that P-selectin, a mediator of the early phase of leukocyte recruitment in acute ischemia is also a major contributor to early BBB dysfunction following stroke. This was investigated by examining the relationship between BBB alterations following transient ischemic stroke and expression of cellular adhesion molecule P-selectin using a combination of magnetic resonance molecular imaging (MRMI, intravital microscopy and immunohistochemistry. MRMI was performed using the contrast, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA conjugated to Sialyl Lewis X (Slex where the latter is known to bind to activated endothelium via E- or P selectins. Middle cerebral artery occlusion was induced in male C57/BL 6 wild-type (WT mice and P-selectin-knockout (KO mice. At 24 hours following middle cerebral artery occlusion, T1 maps were acquired prior to and following contrast injection. In addition to measuring P- and E-selectin expression in brain homogenates, alterations in BBB function were determined immunohistochemically by assessing the extravasation of immunoglobulin G (IgG or staining for polymorphonuclear (PMN leukocytes. In vivo assessment of BBB dysfunction was also investigated optically using intravital microscopy of the pial circulation following the injection of Fluorescein Isothiocyanate (FITC-dextran (MW 2000 kDa. Results MRI confirmed similar infarct sizes and T1 values at 24 hours following stroke for both WT and KO animals. However, the blood to brain transfer constant for Gd DTPA (Kgd demonstrated greater tissue extravasation of Gd DTPA in WT animals than KO mice (P 1 stroke -Δ T1 contralateral control cortex, decreased significantly in the Gd-DTPA(sLeX group compared to Gd-DTPA, indicative of sLeX mediated accumulation of the targeted contrast agent. Regarding BBB

  12. Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice.

    Science.gov (United States)

    Chien, Mei-Yin; Chuang, Cheng-Hung; Chern, Chang-Ming; Liou, Kou-Tong; Liu, Der-Zen; Hou, Yu-Chang; Shen, Yuh-Chiang

    2016-10-01

    Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Encapsulation of interleukin-2 in murine erythrocytes and subsequent deposition in mice receiving a subcutaneous injection

    International Nuclear Information System (INIS)

    DeLoach, J.R.; Andrews, K.; Sheffield, C.L.

    1988-01-01

    Radiolabeled recombinant human interleukin-2 (IL-2) was successfully encapsulated in both mouse and sheep erythrocytes. Of the added IL-2, 70% was recovered bound to or encapsulated within the carrier cells. Erythrocytes containing IL-2 were stable in vitro and most of the IL-2 remained associated with the cells following a 16-h incubation at 37 degrees C. When carrier erythrocytes containing IL-2 were injected subcutaneously into mice, intact [ 35 S]IL-2 was detectable in a number of tissues 3 days after injection

  14. Transfusion of CXCR4-primed endothelial progenitor cells reduces cerebral ischemic damage and promotes repair in db/db diabetic mice.

    Directory of Open Access Journals (Sweden)

    Ji Chen

    Full Text Available This study investigated the role of stromal cell-derived factor-1α (SDF-1α/CXC chemokine receptor 4 (CXCR4 axis in brain and endothelial progenitor cells (EPCs, and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO. In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null or CXCR4 (Ad-CXCR4 followed with high glucose (HG treatment for 4 days. For pathway block experiments, cells were pre-incubated with PI3K inhibitor or nitric oxide synthase (NOS inhibitor for two hours. The CXCR4 expression, function and apoptosis of EPCs were determined. The p-Akt/Akt and p-eNOS/eNOS expression in EPCs were also measured. In in vivo study, EPCs transfected with Ad-null or Ad-CXCR4 were infused into mice via tail vein. On day 2 and 7, the cerebral blood flow, neurologic deficit score, infarct volume, cerebral microvascular density, angiogenesis and neurogenesis were determined. We found: 1 The levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were decreased in db/db mice; 2 The basal level of SDF-1α and MCAO-induced up-regulation of SDF-1α/CXCR4 axis were reduced in the brain of db/db mice; 3 Ad-CXCR4 transfection increased CXCR4 expression in EPCs and enhanced EPC colonic forming capacity; 4 Ad-CXCR4 transfection prevented EPCs from HG-induced dysfunction (migration and tube formation and apoptosis via activation of PI3K/Akt/eNOS signal pathway; 4 Ad-CXCR4 transfection enhanced the efficacy of EPC infusion in attenuating infarct volume and promoting angiogenesis and neurogenesis. Our data suggest that Ad-CXCR4 primed EPCs have better therapeutic effects for ischemia stroke in diabetes than unmodified EPCs do.

  15. Dually supplied T-junctions in arteriolo-arteriolar anastomosis in mice: key to local hemodynamic homeostasis in normal and ischemic states?

    Science.gov (United States)

    Toriumi, Haruki; Tatarishvili, Jemal; Tomita, Minoru; Tomita, Yutaka; Unekawa, Miyuki; Suzuki, Norihiro

    2009-10-01

    The functional role of arteriolo-arteriolar anastomosis (AAA) between the middle cerebral artery (MCA) and anterior cerebral artery in local hemodynamics is unknown, and was investigated here. Blood flow in AAAs was examined using fluorescein isothiocyanate-labeled red blood cells (RBCs) as a flow indicator in 16 anesthetized C57BL/6J mice before and after MCA occlusion up to 7 experimental days. We observed paradoxical flow in AAAs; labeled RBCs entered from both the MCA and anterior cerebral artery sides and the opposing flows met at a branching T-junction, where the flows combined and passed into a penetrating arteriole. The dually fed T-junction was not fixed in position, but functionally jumped to adjacent T-junctions in response to changing hemodynamic conditions. On MCA occlusion, RBC flow from the MCA side immediately stopped. After a period of "hesitation," blood started to move retrogradely in one of the MCA branches toward the MCA stem. The retrograde blood flow was statistically significantly (P<0.05), serving to feed blood to other MCA branches after a lag period. In capillaries, MCA occlusion induced immediate RBC disappearance in the ischemic core and to a lesser extent in the marginal zone near AAAs. At day 3 after ischemia, we recognized the beginning of remodeling with angiogenesis centering on AAAs. AAAs appear to play a key role in local hemodynamic homeostasis, both in the normal state and in the development of collateral channels and revascularization during ischemia.

  16. Reciprocal translocations in germ cells of male mice receiving external γ-irradiation

    International Nuclear Information System (INIS)

    Bayrakova, A.; Filev, G.; Baev, I.

    1987-01-01

    Experiments were undertaken in which yields were recorded of reciprocal translocations in germ cells of male mice exposed to 0.9 Gy of γ-radiation at dose rates ranging from 6.14 x 10 -3 to 6.14 x 10 2 mGy/min (6 levels); comparisons were made with data published up to 1985 from similar studies using other fixed doses. To do this, translocation yields were expressed as relative yields (F) and their relationship to the dose rate (P) for the individual fixed doses was represented by an equation of the type: F = α + β log P. For most of the equations, the regression coefficients were in good agreement and a single relationship was obtained to represent them. From the analysis performed it follows that, within the 0.6-6.0 Gy dose range, the pattern of the F vs. P relationship is unaffected by the dose. This supports the initial assumption that for the dose range up to 6.0 Gy the dose response for the reciprocal translocation yield is a non-threshold straight-line relationship. (Auth.)

  17. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

    DEFF Research Database (Denmark)

    Clausen, Bettina H; Lambertsen, Kate L; Babcock, Alicia A

    2008-01-01

    BACKGROUND: Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We inv...

  18. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    International Nuclear Information System (INIS)

    Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

    2016-01-01

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  19. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

    2016-03-15

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  20. 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 ...

  1. 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.

  2. Aging alters the immunological response to ischemic stroke.

    Science.gov (United States)

    Ritzel, Rodney M; Lai, Yun-Ju; Crapser, Joshua D; Patel, Anita R; Schrecengost, Anna; Grenier, Jeremy M; Mancini, Nickolas S; Patrizz, Anthony; Jellison, Evan R; Morales-Scheihing, Diego; Venna, Venugopal R; Kofler, Julia K; Liu, Fudong; Verma, Rajkumar; McCullough, Louise D

    2018-05-11

    The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls

  3. Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

    OpenAIRE

    Antonenko, Kateryna; Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H

    2016-01-01

    Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes.\\ud Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibril...

  4. Cardiac MRI in mice at 9.4 Tesla with a transmit-receive surface coil and a cardiac-tailored intensity-correction algorithm.

    Science.gov (United States)

    Sosnovik, David E; Dai, Guangping; Nahrendorf, Matthias; Rosen, Bruce R; Seethamraju, Ravi

    2007-08-01

    To evaluate the use of a transmit-receive surface (TRS) coil and a cardiac-tailored intensity-correction algorithm for cardiac MRI in mice at 9.4 Tesla (9.4T). Fast low-angle shot (FLASH) cines, with and without delays alternating with nutations for tailored excitation (DANTE) tagging, were acquired in 13 mice. An intensity-correction algorithm was developed to compensate for the sensitivity profile of the surface coil, and was tailored to account for the unique distribution of noise and flow artifacts in cardiac MR images. Image quality was extremely high and allowed fine structures such as trabeculations, valve cusps, and coronary arteries to be clearly visualized. The tag lines created with the surface coil were also sharp and clearly visible. Application of the intensity-correction algorithm improved signal intensity, tissue contrast, and image quality even further. Importantly, the cardiac-tailored properties of the correction algorithm prevented noise and flow artifacts from being significantly amplified. The feasibility and value of cardiac MRI in mice with a TRS coil has been demonstrated. In addition, a cardiac-tailored intensity-correction algorithm has been developed and shown to improve image quality even further. The use of these techniques could produce significant potential benefits over a broad range of scanners, coil configurations, and field strengths. (c) 2007 Wiley-Liss, Inc.

  5. 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.

  6. Cardiac-specific inducible overexpression of human plasma membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury.

    Science.gov (United States)

    Sadi, Al Muktafi; Afroze, Talat; Siraj, M Ahsan; Momen, Abdul; White-Dzuro, Colin; Zarrin-Khat, Dorrin; Handa, Shivalika; Ban, Kiwon; Kabir, M Golam; Trivieri, Maria G; Gros, Robert; Backx, Peter; Husain, Mansoor

    2018-03-30

    Background: Heart failure (HF) is associated with reduced expression of plasma membrane Ca 2+ -ATPase 4 (PMCA4). Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin. Here we examine temporally regulated cardiac-specific overexpression of hPMCA4b in mouse models of myocardial ischemia reperfusion injury (IRI) ex vivo , and HF following experimental myocardial infarction (MI) in vivo Methods and results: Doxycycline-regulated cardiomyocyte-specific overexpression and activity of hPMCA4b produced adaptive changes in expression levels of Ca 2+ -regulatory genes, and induced hypertrophy without significant differences in Ca 2+ transients or diastolic Ca 2+ concentrations. Total cardiac NOS and nNOS-specific activities were reduced in mice with cardiac overexpression of hPMCA4b while nNOS, eNOS and iNOS protein levels did not differ. hMPCA4b-overexpressing mice also exhibited elevated systolic blood pressure vs. controls, with increased contractility and lusitropy in vivo In isolated hearts undergoing IRI, hPMCA4b overexpression was cardioprotective. NO donor-treated hearts overexpressing hPMCA4b showed reduced LVDP and larger infarct size versus vehicle-treated hearts undergoing IRI, demonstrating that the cardioprotective benefits of hPMCA4b-repressed nNOS are lost by restoring NO availability. Finally, both pre-existing and post-MI induction of hPMCA4b overexpression reduced infarct expansion and improved survival from HF. Conclusions: Cardiac PMCA4b regulates nNOS activity, cardiac mass and contractility, such that PMCA4b overexpression preserves cardiac function following IRI, heightens cardiac performance and limits infarct progression, cardiac hypertrophy and HF, even when induced late post-MI. These data identify PMCA4b as a novel therapeutic target for IRI and HF. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  7. 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.).

  8. 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

  9. 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

  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. 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).

  12. Proliferative Activity of Mammary Carcinoma Cells by AgNOR Count in C3H mice Receiving Ethanol Extract of Sponge Haliclona sp

    Science.gov (United States)

    Sijabat, Lanceria; Susilaningsih, Neni; Trianto, Agus; Murwani, Retno

    2018-02-01

    Quantification of argyrophilic nucleolar organizer region (AgNORs) was considered as one of markers of proliferative activity of cancer cells. Sponge Haliclona sp extract contains anticancer bioactive compounds and our previous study showed that the extract was able to improve histological grade of induced mammary adenocarcinoma in mice. The following research was conducted to study the extract administration on the proliferative activity of the carcinoma cells represented by AgNOR count in mice. This experimental study applied post test only control group design. Twenty C3H mice were divided into four groups namely C (control), H1, H2 and H3. Each group was given 0, 0.15, 1.5, and 15 mg Haliclona sp extract respectively. After three weeks of extract administration, mice were inoculated with breast cancer cells from donor mice. The extract administration were continued for another three weeks. AgNOR count was performed on tumor sections and expressed as mean of AgNOR (mAgNOR) and percentage of AgNOR (pAgNOR). Means of mAgNOR in C, H1, H2 and H3 were 4.070, 3.195, 3.450, and 3.190 respectively. Means of pAgNOR in C, H1, H2 and H3 were 34,40, 25,40, 38,40 and 19,80 respectively. The lowest means of mAgNOR and pAgNOR which is an indication of lower proliferative activity of the cancer cells was found in H3. However no significant difference can be found among treatment groups (p>0.05). Using AgNOR count, the ethanol extract of Haliclona sp could not show significant reduction in proliferation of mammary carcinoma cells of C3H mice. This finding support the view that AgNOR alone could not be used to determine pathology of cancer cells.

  13. IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

    Directory of Open Access Journals (Sweden)

    Norifumi Urao

    2010-10-01

    Full Text Available Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS. IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF-induced ROS production and migration of cultured endothelial cells (ECs; however, its role in post-ischemic neovascularization is unknown.Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+ macrophages and CD31(+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and α-actin positive arterioles. Furthermore, IQGAP1(-/- mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/- mice. In vitro, IQGAP1(-/- BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/- mice.IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

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

    Science.gov (United States)

    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.

  15. Books Received

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. Books Received. Articles in Resonance – Journal of Science Education. Volume 1 Issue 1 January 1996 pp 118-118 Books Received. Books Received · More Details Fulltext PDF. Volume 1 Issue 2 February 1996 pp 120-120 Books Received. Books Received.

  16. Probucol plus cilostazol attenuate hypercholesterolemia‑induced exacerbation in ischemic brain injury via anti-inflammatory effects.

    Science.gov (United States)

    Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-09-01

    Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.

  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. 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

  19. 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.

  20. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  1. Tritium retention in the femoral bone marrow and spleens of mice receiving single intravenous injections of tritiated water and tritiated thymidine

    International Nuclear Information System (INIS)

    Joshima, Hisamasa; Matsushita, Satoru; Fukutsu, Kumiko; Kashima, Masatoshi

    1987-01-01

    To derive parameters necessary for evaluating the possible hazards of tritium, retention of tritium in total and TCA-insoluble fractions of the femoral marrow and spleen of mice were observed after single intravenous injections of tritiated water and tritiated thymidine. Retention curves of tritium in TCA-insoluble fractions of the femoral marrow and spleen were resolved fairly well into two exponential components. After injecting tritiated thymidine, most of the activity was detected in the TCA-insoluble fraction. Tritium in this fraction decreased with half-times of 2.2 days in the femoral marrow and 3.6 days in the spleen as the first component, and 23.9 days and 30.5 days, respectively, as the second component. After tritiated water injections, the tritium incorporated into the TCA-insoluble fraction was quite small. Most of the activity was considered to be in the TCA-soluble fraction. Tritium in this fraction was estimated to decrease with half-times of 2.6 days in the femoral marrow and 2.3 days in the spleen as the first component, and 8.0 days and 8.2 days, respectively, as the second component. It is concluded that the retention curves of tritium in the bone marrow are similar to those in the spleen for tritiated water, but not for tritiated thymidine. (author)

  2. Increased expression of Matrix Metalloproteinase 9 in liver from NZB/W F1 mice received antibody against human parvovirus B19 VP1 unique region protein

    Directory of Open Access Journals (Sweden)

    Hsu Gwo-Jong

    2009-01-01

    Full Text Available Abstract Background Human parvovirus B19 infection has been postulated to the anti-phospholipid syndrome (APS in autoimmunity. However, the influence of anti-B19-VP1u antibody in autoimmune diseases is still obscure. Methods To elucidate the effect of anti-B19-VP1u antibodies in systemic lupus erythematosus (SLE, passive transfer of rabbit anti-B19-VP1u IgG was injected intravenously into NZB/W F1 mice. Results Significant reduction of platelet count and prolonged thrombocytopenia time were detected in anti-B19-VP1u IgG group as compared to other groups, whereas significant increases of anti-B19-VP1u, anti-phospholipid (APhL, and anti-double strand DNA (dsDNA antibody binding activity were detected in anti-B19-VP1u group. Additionally, significant increases of matrix metalloproteinase-9 (MMP9 activity and protein expression were detected in B19-VP1u IgG group. Notably, phosphatidylinositol 3-phosphate kinase (PI3K and phosphorylated extracellular signal-regulated kinase (ERK proteins were involved in the induction of MMP9. Conclusion These experimental results firstly demonstrated the aggravated effects of anti-B19-VP1u antibody in disease activity of SLE.

  3. 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.

  4. 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 ...

  5. Diversity receiver

    NARCIS (Netherlands)

    2005-01-01

    The invention is directed to the reception of high rate radio signals (for example DVB-T signals) while the receiver is moving at a high speed (for example in or with a car). Two or more antennas (12, 16) are closely spaced and arranged behind each other in the direction of motion (v) for receiving

  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. 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. Survival benefits of remote ischemic conditioning in sepsis.

    Science.gov (United States)

    Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2017-06-01

    Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an

  9. 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.

  10. [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)

  11. 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

  12. Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort.

    Directory of Open Access Journals (Sweden)

    Mi Kyoung Son

    Full Text Available Atrial fibrillation (AF is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old without previous stroke who were diagnosed with AF in 2007-2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6% patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32-0.53. Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed.

  13. 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.

  14. 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

  15. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury.

    Science.gov (United States)

    Moore, Scott M; Zhang, Hua; Maeda, Nobuyo; Doerschuk, Claire M; Faber, James E

    2015-07-01

    Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies. We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention. Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction. Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.

  16. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

    Directory of Open Access Journals (Sweden)

    Huang Po-Hsun

    2012-08-01

    Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ

  17. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    OpenAIRE

    V. I. Petrov; O. N. Smuseva; Yu. V. Solovkina

    2013-01-01

    Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months,...

  18. 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.

  19. 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...

  20. [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

  1. 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...

  2. 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.

  3. Effect of Pre-nutrion of Flax Seed Oil (Linum Usitatissimum on the amount of Cerebral ischemic lesion and motor nerve disorders in animal model rat.

    Directory of Open Access Journals (Sweden)

    SV Hosseini

    2015-10-01

    Full Text Available Background & aim: Stroke is the third death agent (factor in industrial countries after cardiovascular disease and cancer. With regard to high content of antioxidant materials in flax seed oil like &alpha-linolenic acid, lignan as well as phenolic combinations like secoisolarisirsinol (SDG, this study performed for studding relationship between of cerebral ischemic lesion and motor-nerve disorders in model of stroke in rat. Methods: in the study, 35 male mice from strain Wistar divided to 5 groups. The groups included control, sham and 3 experimental groups. They received doses 0.25, 0.5 and 0.75 ml/kg from flax seed oil orally. By gavage for 30 days two control and sham groups received aqua distillate (distil water. Two hours after the last gavaged dose, overly group with 7 pieces operated for measurement of the amount of cerebral lesion and motor-nerve disorders. (Middle Cerebral Artery Occlusion Model. Middle cerebral Artery Occlusion by the model resulted in local ischemic stroke in animal. Data analyzed by software SPSS, test ANOVA and disorders by test mann-Whitney. Findings: Average of records of motor-nerve disorders decreased significantly in group with dose 0.5 and 0.75 using flax seed oil (P<0.05. The amount of cerebral ischemic lesion in doses 0.5 and 0.75 than to control group is indicated meaning full different, but percent of the total cerebral lesion in control group in compared group with dose 0.25 is not indicated meaningful different. Percent of the amount of ischemic lesion in region penumbra in group 0.75 and 0.5 than to control group is indicated meaningful different, but percent of the amount of lesion in region penumbra in control group in compared region penumbra in group with dose 0.25 is not indicated meaning full different. Results: Findings of the study indicated that flax seed oil, particular in doses 0.5 and 0.75 resulted to decrease of the amount of cerebral ischemic lesion and decrease of motor-nerve disorders in

  4. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Shelly A Cruz

    2018-01-01

    Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

  5. 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.

  6. Intranasal delivery of E-selectin reduces atherosclerosis in ApoE-/- mice.

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    Xinhui Li

    Full Text Available Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to (pre-tolerization or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.

  7. 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

  8. Management of hypertension in the setting of acute ischemic stroke.

    Science.gov (United States)

    Heitsch, Laura; Jauch, Edward C

    2007-12-01

    The optimal management of blood pressure in the first 24 hours of ischemic stroke remains a controversial topic. Most patients are hypertensive at presentation and subsequently experience a spontaneous decline in blood pressure. Decreasing penumbral blood flow and exacerbating vasogenic edema are significant concerns in whether to treat blood pressure elevations. Although an initially elevated blood pressure has been associated with poor outcome, attempts to acutely lower blood pressure are also associated with worsened outcomes. Thus, the current approach in acute ischemic stroke is permissive hypertension, in which antihypertensive treatment is warranted in patients with systolic blood pressure greater than 220 mm Hg, receiving thrombolytic therapy, or with concomitant medical issues. The use of predictable and titratable medications that judiciously reduce (approximately 10% to 15%) the initial presenting mean arterial pressure is recommended in these situations. Future study must define optimal blood pressure goals, likely on an individual basis.

  9. Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

    Science.gov (United States)

    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.

  10. 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....

  11. Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

    Science.gov (United States)

    Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

    2017-04-01

    Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  12. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

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    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  13. Peripheral Mechanisms of Ischemic Myalgia

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    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

  14. 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...

  15. Redox regulation of ischemic limb neovascularization – What we have learned from animal studies

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    Reiko Matsui

    2017-08-01

    Full Text Available Mouse hindlimb ischemia has been widely used as a model to study peripheral artery disease. Genetic modulation of the enzymatic source of oxidants or components of the antioxidant system reveal that physiological levels of oxidants are essential to promote the process of arteriogenesis and angiogenesis after femoral artery occlusion, although mice with diabetes or atherosclerosis may have higher deleterious levels of oxidants. Therefore, fine control of oxidants is required to stimulate vascularization in the limb muscle. Oxidants transduce cellular signaling through oxidative modifications of redox sensitive cysteine thiols. Of particular importance, the reversible modification with abundant glutathione, called S-glutathionylation (or GSH adducts, is relatively stable and alters protein function including signaling, transcription, and cytoskeletal arrangement. Glutaredoxin-1 (Glrx is an enzyme which catalyzes reversal of GSH adducts, and does not scavenge oxidants itself. Glrx may control redox signaling under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts through Glrx deletion improves in vivo limb revascularization, indicating endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There are several Glrx targets including HIF-1α which may contribute to inhibition of vascularization by reducing GSH adducts. These animal studies provide a caution that excess antioxidants may be counter-productive for treatment of ischemic limbs, and highlights Glrx as a potential therapeutic target to improve ischemic limb vascularization. Keywords: Ischemic limb, Angiogenesis, Oxidants, GSH adducts, Glutaredoxin

  16. 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...

  17. 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.

  18. 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...

  19. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns

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    Verónica Chaparro-Huerta

    2017-02-01

    Conclusion: The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models.

  20. 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...

  1. Gray-Matter Volume Estimate Score: A Novel Semi-Automatic Method Measuring Early Ischemic Change on CT

    OpenAIRE

    Song, Dongbeom; Lee, Kijeong; Kim, Eun Hye; Kim, Young Dae; Lee, Hye Sun; Kim, Jinkwon; Song, Tae-Jin; Ahn, Sung Soo; Nam, Hyo Suk; Heo, Ji Hoe

    2015-01-01

    Background and Purpose We developed a novel method named Gray-matter Volume Estimate Score (GRAVES), measuring early ischemic changes on Computed Tomography (CT) semi-automatically by computer software. This study aimed to compare GRAVES and Alberta Stroke Program Early CT Score (ASPECTS) with regards to outcome prediction and inter-rater agreement. Methods This was a retrospective cohort study. Among consecutive patients with ischemic stroke in the anterior circulation who received intra-art...

  2. Swallowing disorders after ischemic stroke

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    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.

  3. EFFICACY OF MELDONIUM IN ACUTE PERIOD OF ISCHEMIC STROKE

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    S. V. Kotov

    2015-01-01

    Full Text Available Background: As long as systemic thrombolysis is indicated to not more than 10% of patients with ischemic stroke, the search for medical agents for basic treatment of stroke is an important problem of today’s neurology.Aim: To evaluate efficacy of meldonium in patients with acute ischemic stroke.Materials and methods: One hundred and fourteen patients were assessed in the acute period of strokes in the internal carotid artery system. The main group included 70 patients who were given meldonium (Mildronate in addition to their basic treatment regimen. The drug was administered intravenously in daily drop infusions at dose of 10 ml of 10% solution for 10 days, thereafter they were switched to oral treatment at 250 mg daily for 2 to 3 weeks. The control group consisted of 40 patients who received only basic treatment regimen. Both groups were compatible for their age, gender distribution, severity of stroke and degree of neurologic dysfunction.Results: In the patients who were given meldonium in addition to basic treatment of ischemic stroke, neurological deficiency, assessed by NIHSS, scored significantly better than in those from the control group (3.1 ± 0.1 vs. 2.6 ± 0.17, p < 0.05. Also, they had significantly less disability on modified Rankin scale (1.3 ± 0.03 vs. 1.07 ± 0.07, p < 0.01 and more improvement in mobility as per Rivermead mobility index (3.6 ± 0.17 vs. 2.9 ± 0.25, p < 0.05.Conclusion: The addition of meldonium to the set of medical treatment in ischemic stroke patients gives positive results reflecting a decreased neurological deficiency, increased levels of mobility and daily activities.

  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. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

    OpenAIRE

    Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

    2015-01-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

  6. 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.

  7. The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

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    Ji Hyun Kim

    2011-01-01

    Full Text Available Dangkwisoo-San (DS is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO production in human brain microvascular endothelial cells (HBMECs. DS (10–300 μg/mL produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF, although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS inhibitor, N5-(1-iminoethyl-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

  8. 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.

  9. Electronic warfare receivers and receiving systems

    CERN Document Server

    Poisel, Richard A

    2014-01-01

    Receivers systems are considered the core of electronic warfare (EW) intercept systems. Without them, the fundamental purpose of such systems is null and void. This book considers the major elements that make up receiver systems and the receivers that go in them.This resource provides system design engineers with techniques for design and development of EW receivers for modern modulations (spread spectrum) in addition to receivers for older, common modulation formats. Each major module in these receivers is considered in detail. Design information is included as well as performance tradeoffs o

  10. Functional reconstruction of ischemic contracture in the

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    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

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

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    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

  12. 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.

  13. Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

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    Bohacek Ivan

    2012-08-01

    Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

  14. Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

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    Hae Rim Kim

    2013-12-01

    Full Text Available Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

  15. Angiotensin II Removes Kidney Resistance Conferred by Ischemic Preconditioning

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    Hee-Seong Jang

    2014-01-01

    Full Text Available Ischemic preconditioning (IPC by ischemia/reperfusion (I/R renders resistance to the kidney. Strong IPC triggers kidney fibrosis, which is involved in angiotensin II (AngII and its type 1 receptor (AT1R signaling. Here, we investigated the role of AngII/AT1R signal pathway in the resistance of IPC kidneys to subsequent I/R injury. IPC of kidneys was generated by 30 minutes of bilateral renal ischemia and 8 days of reperfusion. Sham-operation was performed to generate control (non-IPC mice. To examine the roles of AngII and AT1R in IPC kidneys to subsequent I/R, IPC kidneys were subjected to either 30 minutes of bilateral kidney ischemia or sham-operation following treatment with AngII, losartan (AT1R blocker, or AngII plus losartan. IPC kidneys showed fibrotic changes, decreased AngII, and increased AT1R expression. I/R dramatically increased plasma creatinine concentrations in non-IPC mice, but not in IPC mice. AngII treatment in IPC mice resulted in enhanced morphological damage, oxidative stress, and inflammatory responses, with functional impairment, whereas losartan treatment reversed these effects. However, AngII treatment in non-IPC mice did not change I/R-induced injury. AngII abolished the resistance of IPC kidneys to subsequent I/R via the enhancement of oxidative stress and inflammatory responses, suggesting that the AngII/AT1R signaling pathway is associated with outcome in injury-experienced kidney.

  16. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke.

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    Chih-Hao Chen

    Full Text Available Timely intravenous (IV thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with "Stroke Code" (SC may increase IV tissue plasminogen activator (tPA administration. The present study aimed to investigate the impact of SC on thrombolysis.The study period was divided into the "pre-SC era" (January 2006 to July 2010 and "SC era" (August 2010 to July 2013. Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis, stroke severity, and clinical outcomes were recorded and compared between the two eras.During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8% arrived at the emergency department within 3 h of stroke onset and 307 (5.2% received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9% to the SC era (n = 216, 33.3% (P<0.001. SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001 and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001. The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2 at discharge (49.5 vs. 39.6%, P = 0.11, with no difference in symptomatic hemorrhage events or in-hospital mortality.The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.

  17. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

    Science.gov (United States)

    Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

    2018-05-03

    Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

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

    Science.gov (United States)

    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.

  19. EFFECTIVENESS OF ISCHEMIC COMPRESSION ON TRAPEZIUS MYOFASCIAL TRIGGER POINTS IN NECK PAIN

    Directory of Open Access Journals (Sweden)

    Pragnya Ravichandran

    2016-04-01

    Full Text Available Background: Neck pain is a common disorder prevailing among individuals of different populations. The myofascial pain syndrome is a disorder related to myofascial trigger points. It is defined as a hyperirritable locus in skeletal muscle and that is associated with a hypersensitive palpable nodule in a taut band of muscle. Manual therapy has got a profound role in treating and ischemic compression technique has been researched widely. Thus the study intends to analyse the effectiveness of Manual Therapy (Ischemic Compression on functional outcome in neck pain. Methods: A single blinded randomized control study was conducted for subjects of sample size 30 who met the inclusion criteria and random allocation was made. The baseline parameters as like pain severity using VAS, pain pressure threshold using pressure Algometer, active cervical lateral flexion using 360 degree goniometer and disability using NDI were recorded. Study group received ischemic compression followed by myofascial stretches while the control group received ultrasonic therapy of 1.4watts/cm2. Both received Cryotherapy post session. After 2 weeks the baseline parameters were again recorded for t-test analysis. Result: There was no statistical significance between groups (p≥0.05. But active cervical lateral flexion showed improved mobility in study group and a high statistical significance within groups (p≤0.01 in relation to all parameters. Conclusion: Both ultrasonic therapy and Ischemic compression technique was found to show better improvement in pain pressure threshold and functional outcome in neck pain.

  20. 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.

  1. 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.

  2. [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.

  3. 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 ...

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Nutrition for brain recovery after ischemic stroke: an added value to rehabilitation.

    Science.gov (United States)

    Aquilani, Roberto; Sessarego, Paolo; Iadarola, Paolo; Barbieri, Annalisa; Boschi, Federica

    2011-06-01

    In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patient's life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

  11. Protective effects of fluoxetine on decompression sickness in mice.

    Directory of Open Access Journals (Sweden)

    Jean-Eric Blatteau

    Full Text Available Massive bubble formation after diving can lead to decompression sickness (DCS that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46 while controls were not treated (n = 45. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004. Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes.

  12. 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...

  13. Histone acetylation and CREB binding protein are required for neuronal resistance against ischemic injury.

    Directory of Open Access Journals (Sweden)

    Ferah Yildirim

    Full Text Available Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT and deacetylase activities (HDAC. Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB-binding protein (CBP as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min subthreshold occlusion of the middle cerebral artery (MCA, followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons.

  14. Rescuing the ischemic penumbra: Our experience

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.)

  17. 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 ...

  18. 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...

  19. 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

  20. Receiver Test Selection Criteria

    Science.gov (United States)

    2015-03-12

    The DOT requests that GPS manufacturers submit receivers for test in the following TWG categories: - Aviation (non-certified), cellular, general location/navigation, high precision, timing, networks, and space-based receivers - Each receiver should b...

  1. 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.

  2. Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

    Science.gov (United States)

    de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

    2014-05-01

    Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. CD13 Promotes Mesenchymal Stem Cell-mediated regeneration of ischemic muscle

    Directory of Open Access Journals (Sweden)

    M. Mamunur eRahman

    2014-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent, tissue-resident cells that can facilitate tissue regeneration and thus show great promise as potential therapeutic agents. Functional MSCs have been isolated and characterized from a wide array of adult tissues and are universally identified by the shared expression of a core panel of MSCs markers. One of these markers is the multifunctional cell surface peptidase CD13 that has been shown to be expressed on human and murine MSCs from many tissues. To investigate whether this universal expression indicates a functional role for CD13 in MSC biology we isolated, expanded and characterized MSCs from bone marrow of wild type (WT and CD13KO mice. Characterization of these cells demonstrated that both WT and CD13KO MSCs expressed the full complement of MSC markers (CD29, CD44, CD49e, CD105, Sca1, showed comparable proliferation rates and were capable of differentiating toward the adipogenic and osteogenic lineages. However, MSCs lacking CD13 were unable to differentiate into vascular cells, consistent with our previous characterization of CD13 as an angiogenic regulator. Compared to WT MSCs, adhesion and migration on various extracellular matrices of CD13KO MSCs were significantly impaired, which correlated with decreased phospho-FAK levels and cytoskeletal alterations. Crosslinking human MSCs with activating CD13 antibodies increased cell adhesion to endothelial monolayers and induced FAK activation in a time dependent manner. In agreement with these in vitro data, intramuscular injection of CD13KO MSCs in a model of severe ischemic limb injury resulted in significantly poorer perfusion, decreased ambulation, increased necrosis and impaired vascularization compared to those receiving WT MSCs. This study suggests that CD13 regulates FAK activation to promote MSC adhesion and migration, thus contributing to MSC-mediated tissue repair. CD13 may present a viable target to enhance the efficacy of mesenchymal

  4. Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

    Science.gov (United States)

    Danigo, Aurore; Nasser, Mohamad; Bessaguet, Flavien; Javellaud, James; Oudart, Nicole; Achard, Jean-Michel; Demiot, Claire

    2015-02-18

    Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.

  5. Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

    Science.gov (United States)

    Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

    2015-08-01

    Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    Directory of Open Access Journals (Sweden)

    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  8. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  9. Predictors of Stroke After Transient Ischemic Attack in Children.

    Science.gov (United States)

    Lehman, Laura L; Watson, Christopher G; Kapur, Kush; Danehy, Amy R; Rivkin, Michael J

    2016-01-01

    Transient ischemic attack (TIA) in children has received far less attention compared with TIA in adults. The risk factors of stroke after TIA in children are relatively unknown. We aimed to determine the percentage of children who have stroke after TIA and the risk factors associated with stroke after TIA. We searched the medical records at Boston Children's Hospital for the year 2010 to find children who were evaluated for TIA to determine associated risk factors of stroke after TIA. We included children who were evaluated in 2009 through 2010 for TIA and had magnetic resonance imaging. We examined follow-up imaging through August 2014 for subsequent stroke. Logistic regression was used to calculate odds ratios for factors in our cohort who are associated with stroke after presentation with TIA. We identified 63 children who experienced a TIA. The mean time of imaging follow-up was 4.5 years after TIA presentation. Of the 63 children, 10 (16%) developed radiological evidence of ischemic cerebral injury within the follow-up period. Four of the 10 (6%) demonstrated diffusion abnormalities on magnetic resonance imaging at TIA presentation, whereas 8 (13%) had a stroke after their TIA. Arteriopathy, female sex, and autoimmune disorders were significantly associated with stroke after TIA. In our cohort of children, stroke occurred after TIA at a rate similar to that seen in adults, but the risk factors for stroke after TIA in children are different. © 2015 American Heart Association, Inc.

  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. Utilization of Emergency Medical Service Increases Chance of Thrombolytic Therapy in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Hsieh, Ming-Ju; Tang, Sung-Chun; Chiang, Wen-Chu; Huang, Kuang-Yu; Chang, Anna Marie; Ko, Patrick Chow-In; Tsai, Li-Kai; Jeng, Jiann-Shing; Ma, Matthew Huei-Ming

    2014-01-01

    Objective To determine whether utilization of emergency medical service (EMS) can expedite and improve the rate of thrombolytic therapy administration in acute ischemic stroke patients. Methods This is a prospective observational study of consecutive patients presenting to the emergency department (ED) with an ischemic stroke within 72 hours of symptom onset. Variables associated with early ED arrival (within 3 hours of stroke onset), and administration of thrombolytic therapy were analyzed. We also evaluated the factors related to onset-to-needle time in patients receiving thrombolytic therapy. Results From January 1, 2010 to July 31, 2011, there were 1081 patients (62.3% men, age 69.6 ± 13 years) included in this study. Among them, 289 (26.7%) arrived in the ED within 3 hours, and 88 (8.1%) received intravenous thrombolytic therapy. Patients who arrived to the ED by EMS (n=279, 25.8 %) were independently associated with earlier ED arrival (adjusted odds ratio [OR] = 3.68, 95% confidence interval [CI] = 2.54 to 5.33), and higher chance of receiving thrombolytic therapy (adjusted OR = 3.89, 95% CI= 1.86 to 8.17). Furthermore, utilization of EMS decreased onset-to-needle time by 26 minutes in patients receiving thrombolytic therapy. Conclusion Utilization of EMS can help acute ischemic stroke patients in early presentation to ED, facilitate thrombolytic therapy, and reduce the onset to needle time. PMID:24296308

  12. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

    Science.gov (United States)

    Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

    2017-11-01

    Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

  13. 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....

  14. 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....

  15. [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...

  16. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.

    Science.gov (United States)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário; Socodato, Renato; Brakebusch, Cord; Lambertsen, Kate Lykke; Relvas, João Bettencourt; Santos, Sofia Duque

    2017-09-28

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective. Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. © 2017 International Society of Neuropathology.

  17. The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

    Science.gov (United States)

    Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

    2010-09-10

    5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

  18. 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

  19. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

    Science.gov (United States)

    Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Montaner, Joan; Rovira, Alex; Ibarra, Bernardo; Quintana, Manuel

    2003-10-01

    The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings

  20. 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.)

  1. 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.

  2. 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

  3. 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....

  4. 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.

  5. A flexible WLAN receiver

    NARCIS (Netherlands)

    Schiphorst, Roelof; Hoeksema, F.W.; Slump, Cornelis H.

    2003-01-01

    Flexible radio receivers are also called Software Defined Radios (SDRs) [1], [2]. The focus of our SDR project [3] is on designing the front end, from antenna to demodulation in bits, of a °exible, multi-standard WLAN receiver. We try to combine an instance of a (G)FSK receiver (Bluetooth) with an

  6. Spontaneous Low Frequency Oscillations in Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Phillip, Dorte; Schytz, Henrik Winther; Iversen, Helle Klingenberg

    2014-01-01

    Background and purpose: Continuous wave near infrared spectroscopy (NIRS) is a non-invasive bed-side optical method to detect changes in oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the outermost layers of the cerebral cortex. Cortical oxyHb low frequency oscillations (LFOs) in the 0.......09-0.11 Hz range are affected by changes in cerebral autoregulation (CA), which is altered following stroke. We examined oxyHb LFOs at bed-side as a marker of CA in the subacute phase in stroke patients with or without recombinant tissue plasminogen activator thrombolytic therapy. Methods: We recruited 29...... patients admitted to the stroke unit with symptoms of ischemic stroke. 11/29 patients received thrombolytic therapy. NIRS examination was conducted 2 days (median time) from stroke onset. NIRS optodes were placed on each side of the head with a 3 cm source-detector distance. Using transfer function...

  7. Thrombolysis with Intravenous Tissue Plasminogen Activator (rt-PA) Predicts Favorable Discharge Disposition in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Ifejika-Jones, Nneka L.; Harun, Nusrat; Mohammed-Rajput, Nareesa A.; Noser, Elizabeth A.; Grotta, James C.

    2011-01-01

    Background and Purpose Acute ischemic stroke patients receiving IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal disability at three months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Subacute Care (Sub). There are no studies assessing the role of rt-PA use as a predictor of post-stroke disposition. Methods Retrospective analysis of all ischemic stroke patients admitted to the University of Texas Houston Medical School (UTHMS) Stroke Service between Jan 2004 and Oct 2009. Baseline demographics and National Institute of Health Stroke Scale (NIHSS) score were collected. Cerebrovascular disease risk factors were used for risk stratification. Results Home vs. IR, SNF, Sub Of 2225 acute ischemic stroke patients, 1019 were discharged home, 1206 to another level of care. Patients who received rt-PA therapy were 1.9 times more likely to be discharged home (P = stroke patients, 719 patients were discharged to acute IR, 371 were discharged to SNF, 116 to Sub. There were no differences in disposition between patients who received rt-PA therapy. Conclusions Stroke patients who receive IV rt-PA for acute ischemic stroke are more 1.9 times more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. PMID:21293014

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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.)

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.)

  20. Highly Sensitive Optical Receivers

    CERN Document Server

    Schneider, Kerstin

    2006-01-01

    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  1. Risk of ischemic stroke after an acute myocardial infarction in patients with diabetes mellitus.

    Science.gov (United States)

    Jakobsson, Stina; Bergström, Lisa; Björklund, Fredrik; Jernberg, Tomas; Söderström, Lars; Mooe, Thomas

    2014-01-01

    Incidence, any trend over time, and predictors of ischemic stroke after an acute myocardial infarction (AMI) in diabetic patients are unknown. Data for 173,233 unselected patients with an AMI, including 33,503 patients with diabetes mellitus, were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) during 1998 to 2008. Ischemic stroke events were recorded during 1 year of follow-up. Patients with diabetes mellitus more often had a history of cardiovascular disease, received less reperfusion therapy, and were treated with acetylsalicylic acid, P2Y12 inhibitors, and statins to a lesser extent compared with patients without diabetes mellitus. However, the use of evidence-based therapies increased markedly in both groups during the study period. The incidence of ischemic stroke during the first year after AMI decreased from 7.1% to 4.7% in patients with diabetes mellitus and from 4.2% to 3.7% in patients without diabetes mellitus. Risk reduction was significantly larger in the diabetic subgroup. Reperfusion therapy, acetylsalicylic acid, P2Y12 inhibitors, and statins were independently associated with the reduced stroke risk. Ischemic stroke is a fairly common complication after an AMI in patients with diabetes mellitus, but the risk of stroke has decreased during recent years. The increased use of evidence-based therapies contributes importantly to this risk reduction, but there is still room for improvement.

  2. 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.)

  3. 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.

  4. Remote Ischemic Conditioning and Renal Protection.

    Science.gov (United States)

    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.

  5. 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.

  6. Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen

    Directory of Open Access Journals (Sweden)

    Ziya Ayhan

    2015-01-01

    Full Text Available Optic disc drusen (ODD are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION who received the diagnosis of bilateral optic disc drusen five years earlier and thereby reiterated the association of ODD and acute NAION.

  7. 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...

  8. Delphi Accounts Receivable Module -

    Data.gov (United States)

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  9. 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

  10. Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.

    Science.gov (United States)

    Zager, Richard A; Johnson, Ali C; Becker, Kirsten

    2013-06-01

    Recent experimental work suggests a paradox: although uremia evokes systemic toxicities, in the setting of AKI, it can induce intrarenal cytoprotective and anti-inflammatory effects. Whether these influences can attenuate post-ischemic kidney disease progression remains unknown. To explore this possibility, male CD-1 mice were subjected to a 30-min unilateral (left) kidney ischemia model, previously shown to reduce renal mass by ∼50% over 2-3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted with the degree of initial azotemia 24-h BUN. A striking correlation between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001). With 20 min of right kidney ischemia, left kidney size was completely preserved. This preservation did not result from increased tubular cell proliferation or decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry, respectively. Rather, an early reduction in proximal tubule cell dropout (as judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent preservation of tubule mass, was observed. In summary, these findings advance a novel concept: acute uremia can confer early post-ischemic cytoprotection resulting in a slowed progression of post-ischemic kidney disease.

  11. Hemorrhagic versus ischemic stroke: Who can best benefit from blended conventional physiotherapy with robotic-assisted gait therapy?

    Directory of Open Access Journals (Sweden)

    Frédéric Dierick

    Full Text Available Contrary to common belief of clinicians that hemorrhagic stroke survivors have better functional prognoses than ischemic, recent studies show that ischemic survivors could experience similar or even better functional improvements. However, the influence of stroke subtype on gait and posture outcomes following an intervention blending conventional physiotherapy with robotic-assisted gait therapy is missing.This study compared gait and posture outcome measures between ambulatory hemorrhagic patients and ischemic patients, who received a similar 4 weeks' intervention blending a conventional bottom-up physiotherapy approach and an exoskeleton top-down robotic-assisted gait training (RAGT approach with Lokomat.Forty adult hemiparetic stroke inpatient subjects were recruited: 20 hemorrhagic and 20 ischemic, matched by age, gender, side of hemisphere lesion, stroke severity, and locomotor impairments. Functional Ambulation Category, Postural Assessment Scale for Stroke, Tinetti Performance Oriented Mobility Assessment, 6 Minutes Walk Test, Timed Up and Go and 10-Meter Walk Test were performed before and after a 4-week long intervention. Functional gains were calculated for all tests.Hemorrhagic and ischemic subjects showed significant improvements in Functional Ambulation Category (P<0.001 and P = 0.008, respectively, Postural Assessment Scale for Stroke (P<0.001 and P = 0.003, 6 Minutes Walk Test (P = 0.003 and P = 0.015 and 10-Meter Walk Test (P = 0.001 and P = 0.024. Ischemic patients also showed significant improvements in Timed Up and Go. Significantly greater mean Functional Ambulation Category and Tinetti Performance Oriented Mobility Assessment gains were observed for hemorrhagic compared to ischemic, with large (dz = 0.81 and medium (dz = 0.66 effect sizes, respectively.Overall, both groups exhibited quasi similar functional improvements and benefits from the same type, length and frequency of blended conventional physiotherapy and RAGT

  12. Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

    Science.gov (United States)

    Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

    2018-02-14

    Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

  13. Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome.

    Science.gov (United States)

    Izzy, Saef; Rubin, Daniel B; Ahmed, Firas S; Akbik, Feras; Renault, Simone; Sylvester, Katelyn W; Vaitkevicius, Henrikas; Smallwood, Jennifer A; Givertz, Michael M; Feske, Steven K

    2018-05-01

    Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses. From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85). Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic

  14. Hemorrhagic versus ischemic stroke: Who can best benefit from blended conventional physiotherapy with robotic-assisted gait therapy?

    Science.gov (United States)

    Dierick, Frédéric; Dehas, Mélanie; Isambert, Jean-Luc; Injeyan, Soizic; Bouché, Anne-France; Bleyenheuft, Yannick; Portnoy, Sigal

    2017-01-01

    Contrary to common belief of clinicians that hemorrhagic stroke survivors have better functional prognoses than ischemic, recent studies show that ischemic survivors could experience similar or even better functional improvements. However, the influence of stroke subtype on gait and posture outcomes following an intervention blending conventional physiotherapy with robotic-assisted gait therapy is missing. This study compared gait and posture outcome measures between ambulatory hemorrhagic patients and ischemic patients, who received a similar 4 weeks' intervention blending a conventional bottom-up physiotherapy approach and an exoskeleton top-down robotic-assisted gait training (RAGT) approach with Lokomat. Forty adult hemiparetic stroke inpatient subjects were recruited: 20 hemorrhagic and 20 ischemic, matched by age, gender, side of hemisphere lesion, stroke severity, and locomotor impairments. Functional Ambulation Category, Postural Assessment Scale for Stroke, Tinetti Performance Oriented Mobility Assessment, 6 Minutes Walk Test, Timed Up and Go and 10-Meter Walk Test were performed before and after a 4-week long intervention. Functional gains were calculated for all tests. Hemorrhagic and ischemic subjects showed significant improvements in Functional Ambulation Category (Pbenefits from the same type, length and frequency of blended conventional physiotherapy and RAGT protocol. The use of intensive treatment plans blending top-down physiotherapy and bottom-up robotic approaches is promising for post-stroke rehabilitation.

  15. Potential serum biomarkers and metabonomic profiling of serum in ischemic stroke patients using UPLC/Q-TOF MS/MS.

    Directory of Open Access Journals (Sweden)

    Hongxue Sun

    Full Text Available Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke.Metabonomic analysis was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis was employed to study 60 patients with or without ischemic stroke (30 cases and 30 controls.Serum metabolic profiling identified a series of 12 metabolites with significant alterations, and the related metabolic pathways involved glycerophospholipid, sphingolipid, phospholipid, fat acid, acylcarnitine, heme, and purine metabolism. Subsequently, multiple logistic regression analyses of these metabolites showed uric acid, sphinganine and adrenoyl ethanolamide were potential biomarkers of ischemic stroke with an area under the receiver operating characteristic curve of 0.941.These findings provide insights into the early diagnosis and potential pathophysiology of ischemic stroke.

  16. 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.)

  17. 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.

  18. 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.

  19. 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

  20. 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.)

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. [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.

  8. 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)

  9. Protective effects of hydroxysaffor yellow A on brain injury in mice irradiated by 300 MeV/n 12C6+ ions

    International Nuclear Information System (INIS)

    Gan Lu; Wang Zhenhua; Zhang Hong; Ma Chengjun; Li Guang

    2012-01-01

    Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction, to which no ideal prevention method is available until now. Hydroxysaffor yellow A (HSYA) is the main active ingredient of the traditional Chinese medicine safflower, with protective effects against cerebral ischemic injury. In this work, we investigated the protective effects of HSYA on brain injury in mice irradiated by 300 MeV/u 12 C 6+ ion beam. The whole head of male Kunming mouse was irradiated to 4.0 Gy after receiving daily intra-peritoneal injection HSYA for 3 d. One month later, the Morris water maze test was used to detect the spatial memory in mice. The Evans blue was used as the tracer to evaluate the permeability of blood-brain barrier. The SOD activity and MDA content in brain tissue were assayed by test kits. The results showed that the 12 C 6+ irradiation significantly impaired the spatial learning and memory in mice, increased the permeability of blood-brain barrier and the MDA content in brain tissue, whereas decreased the SOD activity in brain tissue. The pretreatment with HSYA could improve the spatial memory deficits and inhibit the changes of the blood-brain barrier, the SOD activity and the MDA content in brain tissue in mice. All these demonstrate that HSYA possesses the protective effect against brain injury induced by 12 C 6+ particle therapy. (authors)

  10. 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.

  11. 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

  12. 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.

  13. Noninvasive Ventilatory Correction as an Adjunct to an Experimental Systemic Reperfusion Therapy in Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Kristian Barlinn

    2010-01-01

    Full Text Available Background. Obstructive sleep apnea (OSA is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA occlusion received intravenous tissue plasminogen activator (tPA and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies.

  14. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

    Science.gov (United States)

    Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

    2017-10-01

    Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

  15. Role of Epinephrine and Extracorporeal Membrane Oxygenation in the Management of Ischemic Refractory Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Jason A. Bartos, MD, PhD

    2017-06-01

    Full Text Available Summary: Extracorporeal membrane oxygenation (ECMO is used in cardiopulmonary resuscitation (CPR of refractory cardiac arrest. The authors used a 2 × 2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF. Pigs underwent 5 min of untreated VF and 10 min of CPR, and were randomized to receive epinephrine versus placebo for another 35 min. Animals were further randomized to left anterior descending artery (LAD reperfusion at minute 45 with ongoing CPR versus venoarterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO whereas epinephrine showed no effect. Key Words: advanced cardiopulmonary life support, cardiac arrest, cardiopulmonary resuscitation, ECMO, extracorporeal membrane oxygenation, ischemic refractory ventricular fibrillation, ST-segment elevation myocardial infarction, ventricular fibrillation

  16. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    John Thundyil

    Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

  17. Solar energy receiver

    Science.gov (United States)

    Schwartz, Jacob

    1978-01-01

    An improved long-life design for solar energy receivers provides for greatly reduced thermally induced stress and permits the utilization of less expensive heat exchanger materials while maintaining receiver efficiencies in excess of 85% without undue expenditure of energy to circulate the working fluid. In one embodiment, the flow index for the receiver is first set as close as practical to a value such that the Graetz number yields the optimal heat transfer coefficient per unit of pumping energy, in this case, 6. The convective index for the receiver is then set as closely as practical to two times the flow index so as to obtain optimal efficiency per unit mass of material.

  18. Cryogenic microwave channelized receiver

    International Nuclear Information System (INIS)

    Rauscher, C.; Pond, J.M.; Tait, G.B.

    1996-01-01

    The channelized receiver being presented demonstrates the use of high temperature superconductor technology in a microwave system setting where superconductor, microwave-monolithic-integrated-circuit, and hybrid-integrated-circuit components are united in one package and cooled to liquid-nitrogen temperatures. The receiver consists of a superconducting X-band four-channel demultiplexer with 100-MHz-wide channels, four commercial monolithically integrated mixers, and four custom-designed hybrid-circuit detectors containing heterostructure ramp diodes. The composite receiver unit has been integrated into the payload of the second-phase NRL high temperature superconductor space experiment (HTSSE-II). Prior to payload assembly, the response characteristics of the receiver were measured as functions of frequency, temperature, and drive levels. The article describes the circuitry, discusses the key issues related to design and implementation, and summarizes the experimental results

  19. Alexandrite Lidar Receiver

    National Research Council Canada - National Science Library

    Wilkerson, Thomas

    2000-01-01

    ...". The chosen vendor, Orca Photonics, In. (Redmond, WA), in close collaboration with USU personnel, built a portable, computerized lidar system that not only is suitable as a receiver for a near IR alexandrite laser, but also contains an independent Nd...

  20. Receiver Gain Modulation Circuit

    Science.gov (United States)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  1. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues

    Science.gov (United States)

    Faber, James E.; Zhang, Hua; Lassance-Soares, Roberta M.; Prabhakar, Pranay; Najafi, Amir H.; Burnett, Mary Susan; Epstein, Stephen E.

    2011-01-01

    Objective Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals, and their remodeling in 3-, 16-, 24-, and 31-months-old mice. Methods and Results Aging caused an “age-dose-dependent” greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T-cells or macrophages to remodeling collaterals. However, eNOS signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated eNOS and VASP in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (e.g., 6- and 3-fold, respectively, in 24-months-old mice) after artery occlusion. This was not associated with rarefaction of similarly-sized arterioles. Collateral remodeling was also reduced. Conclusions Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury. PMID:21617137

  2. 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.

  3. 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...

  4. 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.)

  5. Insulin resistance is associated with a poor response to intravenous thrombolysis in acute ischemic stroke.

    Science.gov (United States)

    Calleja, Ana I; García-Bermejo, Pablo; Cortijo, Elisa; Bustamante, Rosa; Rojo Martínez, Esther; González Sarmiento, Enrique; Fernández-Herranz, Rosa; Arenillas, Juan F

    2011-11-01

    Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis. We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥ 3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points. A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67-43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23-54.44]; P = 0.029). High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.

  6. Ischemic Gastric Conditioning by Preoperative Arterial Embolization Before Oncologic Esophagectomy: A Single-Center Experience

    Energy Technology Data Exchange (ETDEWEB)

    Ghelfi, Julien, E-mail: JGhelfi@chu-grenoble.fr [CHU de Grenoble, Clinique Universitaire de Radiologie et Imagerie Médicale (France); Brichon, Pierre-Yves, E-mail: PYBrichon@chu-grenoble.fr [CHU de Grenoble, Clinique Universitaire de Chirurgie Thoracique, Vasculaire et Endocrinienne (France); Frandon, Julien, E-mail: Julien.frandon@chu-nimes.fr [CHU de Nîmes, Clinique Universitaire de Radiologie et Imagerie Médicale (France); Boussat, Bastien, E-mail: BBoussat@chu-grenoble.fr [CHU de Grenoble, Département d’Information Médicale, Pôle de Santé Publique (France); Bricault, Ivan, E-mail: IBricault@chu-grenoble.fr; Ferretti, Gilbert, E-mail: GFerretti@chu-grenoble.fr [CHU de Grenoble, Clinique Universitaire de Radiologie et Imagerie Médicale (France); Guigard, Sébastien, E-mail: SGuigard@chu-grenoble.fr [CHU de Grenoble, Clinique Universitaire de Chirurgie Thoracique, Vasculaire et Endocrinienne (France); Sengel, Christian, E-mail: CSengel@chu-grenoble.fr [CHU de Grenoble, Clinique Universitaire de Radiologie et Imagerie Médicale (France)

    2017-05-15

    PurposeSurgical esophagectomy is the gold standard treatment of early-stage esophageal cancer. The procedure is complicated with significant morbidity; the most severe complication being the anastomotic leakage. Anastomotic fistulas are reported in 5–25% of cases and are mainly due to gastric transplant ischemia. Here, we report our experience of ischemic pre-conditioning using preoperative arterial embolization (PreopAE) before esophagectomy.Materials and MethodsThe medical records of all patients who underwent oncologic esophagectomy from 2008 to 2015 were retrospectively reviewed. Patients were divided into two groups: patients who received PreopAE, and a control group of patients who did not benefit from ischemic pre-conditioning. The target arteries selected for PreopAE were the splenic artery, left gastric artery, and right gastric artery. Evaluation of the results was based on anastomotic leakage, postoperative mortality, technical success of PreopAE, and complications related to the embolization procedure.ResultsForty-six patients underwent oncologic esophagectomy with PreopAE and 13 patients did not receive ischemic conditioning before surgery. Thirty-eight PreopAE were successfully performed (83%), but right gastric artery embolization failed for 8 patients. Anastomotic leakage occurred in 6 PreopAE patients (13%) and in 6 patients (46%) in the control group (p = 0.02). The mortality rate was 2% in the PreopAE group and 23% in the control group (p = 0.03). Eighteen patients suffered from partial splenic infarction after PreopAE, all treated conservatively.ConclusionPreoperative ischemic conditioning by arterial embolization before oncologic esophagectomy seems to be effective in preventing anastomotic leakage.

  7. Cervicocranial fibromuscular dysplasia in Taiwanese ischemic stroke patients.

    Science.gov (United States)

    Liu, Chi-Hung; Wu, Dean; Chin, Shy-Chyi; Fu, Ser-Chen; Wu, Tai-Cheng; Chang, Chien-Hung; Peng, Tsung-I; Chang, Yeu-Jhy; Lee, Tsong-Hai

    2012-01-01

    Clinical research of cervicocranial fibromuscular dysplasia (FMD) is rare in Asian populations. Our study reviewed Taiwanese ischemic stroke patients with cervicocranial FMD and compared them with previous reports. Between 2000 and 2011, we collected 19 consecutive cervicocranial FMD patients who received demographic registration, a blood test for excluding vasculitis, and comprehensive angiography. Cerebral ultrasound, vascular images and clinical outcomes (Barthel index, modified Rankin scale, recurrent stroke, or death) were monitored during follow-up. Of the 19 patients, 16 (84%) had carotid FMD, while 7 (37%) had vertebral FMD. Only 2 investigated patients (13%) had renal FMD and 1 (5%) had cerebral aneurysm. 14 (74%) presented acute arterial dissection. All patients received medical treatment and had neither recurrent stroke nor dissection during follow-up. In the literature review of 225 FMD patients, 3.6% had recurrent stroke during follow-up, and some reported surgical procedure or angioplasty could give a good clinical outcome in progressing ischemia irrelevant to the cause of stenosis. In Taiwanese cervicocranial FMD patients, arterial dissection was one of the most common clinical presentations. Most of our patients had isolated involvement of the cervicocranial artery and carried a favorable outcome under medical treatment. Copyright © 2012 S. Karger AG, Basel.

  8. 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)

  9. 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.

  10. 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...

  11. The protective effect of huperzine A against hepatic ischemia reperfusion injury in mice.

    Science.gov (United States)

    Yang, Y; Yang, J; Jiang, Q

    2014-06-01

    Nowadays, hepatic ischemia reperfusion (HI/R) injury is regarded as a serious concern in clinical practices. Huperzine A (HupA) is an alkaloid isolated from the Chinese folk medicine huperzia serrate, which has possessed diverse pharmacological actions. A mouse model of HI/R was caused by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group experienced the identical procedure without hepatic ischemia. The HupA group received an injection into the tail vein 5 minutes prior to HI/R at the doses of 167 and 500 μg/kg. The vehicle group was injected with physiological saline instead of HupA. The liver function was assessed by determinations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Tissue levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were also measured spectrophotometrically. In addition, the activities of hepatic inflammatory mediators such as nuclear factor kappa B (NF-κB) p65, tumor necrosis factors-α (TNF-α, interleukin-1β (IL-1β) and IL-6 were also measured. Furthermore, the apoptotic damage was evaluated by measuring caspase-3 activity in hepatic tissues. Treatment with HupA in mice at the doses of 167 and 500 μg/kg remarkably reduced serum ALT and AST activities in HupA-treated ischemic mice. Furthermore, HupA treatment could enhance the activities of hepatic tissue SOD, CAT, and GSH but decrease MDA tissue content. The activities of inflammatory cytokines including NF-κB p65, TNF-α, IL-1β and IL-6 were all decreased in ischemic mice treated with HupA. Colorimetric test results illustrated that a marked reduction of caspase-3 activity was found in the HupA-treated group compared with the vehicle group. Our present data suggest that HupA has a protective role against HI/R injury of mice and antioxidative, anti-inflammatory, and antiapoptotic

  12. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Østergaard, Kamilla; Clausen, Bettina Hjelm

    2014-01-01

    known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. METHODS: The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory...... and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry......-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected...

  13. 'Chaos' in superregenerative receivers

    International Nuclear Information System (INIS)

    Commercon, Jean-Claude; Badard, Robert

    2005-01-01

    The superregenerative principle has been known since the early 1920s. The circuit is extremely simple and extremely sensitive. Today, superheterodyne receivers generally supplant superregenerative receivers in most applications because there are several undesirable characteristics: poor selectivity, reradiation, etc. Superregenerative receivers undergo a revival in recent papers for wireless systems, where low cost and very low power consumption are relevant: house/building meters (such as water, energy, gas counter), personal computer environment (keyboard, mouse), etc. Another drawback is the noise level which is higher than that of a well-designed superheterodyne receiver; without an antenna input signal, the output of the receiver hears in an earphone as a waterfall noise; this sound principally is the inherent input noise amplified and detected by the circuit; however, when the input noise is negligible with respect of an antenna input signal, we are faced to an other source of 'noise' self-generated by the superregenerative working. The main objective of this paper concerns this self-generated noise coming from an exponential growing followed by a re-injection process for which the final state is a function of the phase of the input signal

  14. Mitochondrial-Targeted Antioxidant Maintains Blood Flow, Mitochondrial Function, and Redox Balance in Old Mice Following Prolonged Limb Ischemia

    Directory of Open Access Journals (Sweden)

    Shunsuke Miura

    2017-09-01

    Full Text Available Aging is a major factor in the decline of limb blood flow with ischemia. However, the underlying mechanism remains unclear. We investigated the role of mitochondrial reactive oxygen species (ROS with regard to limb perfusion recovery in aging during ischemia. We performed femoral artery ligation in young and old mice with or without treatment with a scavenger of mitochondrial superoxide, MitoTEMPO (180 μg/kg/day, from pre-operative day 7 to post-operative day (POD 21 infusion using an implanted mini-pump. The recoveries of cutaneous blood flow in the ischemic hind limb were lower in old mice than in young mice but were improved in MitoTEMPO-treated old mice. Mitochondrial DNA damage appeared in ischemic aged muscles but was eliminated by MitoTEMPO treatment. For POD 2, MitoTEMPO treatment suppressed the expression of p53 and the ratio of Bax/Bcl2 and upregulated the expression of hypoxia-inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF in ischemic aged skeletal muscles. For POD 21, MitoTEMPO treatment preserved the expression of PGC-1α in ischemic aged skeletal muscle. The ischemic soleus of old mice showed a lower mitochondrial respiratory control ratio in POD 21 compared to young mice, which was recovered in MitoTEMPO-treated old mice. Scavenging of mitochondrial superoxide attenuated mitochondrial DNA damage and preserved the mitochondrial respiration, in addition to suppression of the expression of p53 and preservation of the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α in ischemic skeletal muscles with aging. Resolution of excessive mitochondrial superoxide could be an effective therapy to recover blood flow of skeletal muscle during ischemia in senescence.

  15. Solar thermal central receivers

    International Nuclear Information System (INIS)

    Vant-Hull, L.L.

    1993-01-01

    Market issues, environmental impact, and technology issues related to the Solar Central Receiver concept are addressed. The rationale for selection of the preferred configuration and working fluid are presented as the result of a joint utility-industry analysis. A $30 million conversion of Solar One to an external molten salt receiver would provide the intermediate step to a commercial demonstration plant. The first plant in this series could produce electricity at 11.2 cents/kWhr and the seventh at 8.2 cents/kWhr, completely competitive with projected costs of new utility plants in 1992

  16. Wideband CMOS receivers

    CERN Document Server

    Oliveira, Luis

    2015-01-01

    This book demonstrates how to design a wideband receiver operating in current mode, in which the noise and non-linearity are reduced, implemented in a low cost single chip, using standard CMOS technology.  The authors present a solution to remove the transimpedance amplifier (TIA) block and connect directly the mixer’s output to a passive second-order continuous-time Σ∆ analog to digital converter (ADC), which operates in current-mode. These techniques enable the reduction of area, power consumption, and cost in modern CMOS receivers.

  17. 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

  18. Receiver gain function: the actual NMR receiver gain

    OpenAIRE

    Mo, Huaping; Harwood, John S.; Raftery, Daniel

    2010-01-01

    The observed NMR signal size depends on the receiver gain parameter. We propose a receiver gain function to characterize how much the raw FID is amplified by the receiver as a function of the receiver gain setting. Although the receiver is linear for a fixed gain setting, the actual gain of the receiver may differ from what the gain setting suggests. Nevertheless, for a given receiver, we demonstrate that the receiver gain function can be calibrated. Such a calibration enables accurate compar...

  19. 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.

  20. 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

  1. Campus Projects Receiving "Earmarks."

    Science.gov (United States)

    Schonberger, Benjamin

    1991-01-01

    Specific campus projects that Congress has directed federal agencies to support this year at over 120 colleges and universities are listed. The agencies neither requested support nor sponsored merit-based competitions for the awards. In some cases, the institutions have a history of receiving special federal treatment. (MSE)

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Macrophage Metalloelastase (MMP-12) Deficiency Mitigates Retinal Inflammation and Pathological Angiogenesis in Ischemic Retinopathy

    Science.gov (United States)

    Li, Jingming; Wang, Joshua J.; Peng, Qisheng; Chen, Chen; Humphrey, Mary Beth; Heinecke, Jay; Zhang, Sarah X.

    2012-01-01

    Pathological angiogenesis is a major cause of vision loss in ischemic and inflammatory retinal diseases. Recent evidence implicates macrophage metalloelastase (MMP-12), a macrophage-derived elastinolytic protease in inflammation, tissue remodeling and angiogenesis. However, little is known about the role of MMP-12 in retinal pathophysiology. The present study aims to explore the enzyme’s contributions to retinal angiogenesis in oxygen-induced retinopathy (OIR) using MMP-12 knockout (KO) mice. We find that MMP-12 expression was upregulated in OIR, accompanied by elevated macrophage infiltration and increased inflammatory markers. Compared to wildtype mice, MMP-12 KO mice had decreased levels of adhesion molecule and inflammatory cytokines and reduced vascular leakage in OIR. Concomitantly, these mice had markedly reduced macrophage content in the retina with impaired macrophage migratory capacity. Significantly, loss of MMP-12 attenuated retinal capillary dropout in early OIR and mitigated pathological retinal neovascularization (NV). Similar results were observed in the study using MMP408, a pharmacological inhibitor of MMP-12. Intriguingly, in contrast to reducing pathological angiogenesis, lack of MMP-12 accelerated revascularization of avascular retina in OIR. Taken together, we conclude that MMP-12 is a key regulator of macrophage infiltration and inflammation, contributing to retinal vascular dysfunction and pathological angiogenesis. PMID:23285156

  8. 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).

  9. Self-Determination Theory Application In The Discharge Of Patients With Transient Ischemic Attack

    Directory of Open Access Journals (Sweden)

    Tahere Sarboozi Hosein Abadi

    2017-02-01

    Full Text Available Background: The principle of transient ischemic attack treatment is lifestyle modification and pharmacological treatment that would reduce recurrence and incidence of stroke. Lifestyle changes require follow-up care and continuity of nurse and patient relationships, but the current training does not meet this need. The trainings based on motivating theory such as self-determination, besides continuity of the relationship with patient, improve his/her incentive, specially of it is carried out at the discharge time. Therefore, this study has been done by the purpose of defining the impact of discharge plan based on self-determination theory on the lifestyle patients with transient ischemic attack. Methodology: The analysis has been done on 57, 18-90 years old clinical random patients in Tehran hospitals (29 cases and 28 controls in 2015. Data were collected by demographic questionnaire at the beginning and health-promoting lifestyle questionnaire(second edition were collected at the end of the study. Discharge plan based on self-determination theory, including patients and families meeting in hospital and telephone counseling during the 12 weeks after discharge was accomplished in cases group. The control group received only routine hospital care. Data were analyzed by t-test and chi- squre test. Results: The score of lifestyle was similar in both groups (p> .05 at beginning of the study, but at the end of the study, the average score of cases group (17.1 ± 164.2 significantly higher than the control group (17.6 ± 118.3 (p < 0.001. Furthermore, At the end of study, the mean scores of nutrition, physical activity, stress management, interpersonal relationships, spiritual growth and responsibility in the lifestyle cases group was significantly higher than the control group (p <.001. The frequency of transient ischemic attacks after discharge in the cases group (13.8%, significantly lower than the control group (46.4%, respectively (p = .016

  10. The Impact of Total Ischemic Time, Donor Age and the Pathway of Donor Death on Graft Outcomes After Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Wong, Germaine; Teixeira-Pinto, Armando; Chapman, Jeremy R; Craig, Jonathan C; Pleass, Henry; McDonald, Stephen; Lim, Wai H

    2017-06-01

    Prolonged ischemia is a known risk factor for delayed graft function (DGF) and its interaction with donor characteristics, the pathways of donor death, and graft outcomes may have important implications for allocation policies. Using data from the Australian and New Zealand Dialysis and Transplant registry (1994-2013), we examined the relationship between total ischemic time with graft outcomes among recipients who received their first deceased donor kidney transplants. Total ischemic time (in hours) was defined as the time of the donor renal artery interruption or aortic clamp, until the time of release of the clamp on the renal artery in the recipient. A total of 7542 recipients were followed up over a median follow-up time of 5.3 years (interquartile range of 8.2 years). Of these, 1823 (24.6%) experienced DGF and 2553 (33.9%) experienced allograft loss. Recipients with total ischemic time of 14 hours or longer experienced an increased odd of DGF compared with those with total ischemic time less than 14 hours. This effect was most marked among those with older donors (P value for interaction = 0.01). There was a significant interaction between total ischemic time, donor age, and graft loss (P value for interaction = 0.03). There was on average, a 9% increase in the overall risk of graft loss per hour increase in the total ischemic time (adjusted hazard ratio, 1.09; 95% confidence interval, 1.01-1.18; P = 0.02) in recipients with older donation after circulatory death grafts. There is a clinically important interaction between donor age, the pathway of donor death, and total ischemic time on graft outcomes, such that the duration of ischemic time has the greatest impact on graft survival in recipients with older donation after circulatory death kidneys.

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

    Science.gov (United States)

    Valentino, Francesca; Gentile, Luana; Terruso, Valeria; Mastrilli, Sergio; Aridon, Paolo; Ragonese, Paolo; Sarno, Caterina; Savettieri, Giovanni; D'Amelio, Marco

    2017-11-13

    hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of uni- and multivariate logistic regression analyses. 119 consecutive patients were included (73 males, 61.3%). Hemorrhagic transformation was observed in 7 patients (5.9%). Only clinical worsening was significantly associated with hemorrhagic transformation (OR 6.8, 95% CI 1.3-34.5). Our findings indicate that patients with posterior have a low risk of spontaneous hemorrhagic transformation, suggesting that these patients might have greater advantage from intravenous thrombolysis.

  19. Impact of Smartphone Applications on Timing of Endovascular Therapy for Ischemic Stroke: A Preliminary Study.

    Science.gov (United States)

    Alotaibi, Naif M; Sarzetto, Francesca; Guha, Daipayan; Lu, Michael; Bodo, Andre; Gupta, Shaurya; Dyer, Erin; Howard, Peter; da Costa, Leodante; Swartz, Richard H; Boyle, Karl; Nathens, Avery B; Yang, Victor X D

    2017-11-01

    The metrics of imaging-to-puncture and imaging-to-reperfusion were recently found to be associated with the clinical outcomes of endovascular thrombectomy for acute ischemic stroke. However, measures for improving workflow within hospitals to achieve better timing results are largely unexplored for endovascular therapy. The aim of this study was to examine our experience with a novel smartphone application developed in house to improve our timing metrics for endovascular treatment. We developed an encrypted smartphone application connecting all stroke team members to expedite conversations and to provide synchronized real-time updates on the time window from stroke onset to imaging and to puncture. The effects of the application on the timing of endovascular therapy were evaluated with a secondary analysis of our single-center cohort. Our primary outcome was imaging-to-puncture time. We assessed the outcomes with nonparametric tests of statistical significance. Forty-five patients met our criteria for analysis among 66 consecutive patients with acute ischemic stroke who received endovascular therapy at our institution. After the implementation of the smartphone application, imaging-to-puncture time was significantly reduced (preapplication median time, 127 minutes; postapplication time, 69 minutes; P smartphone applications may reduce treatment times for endovascular therapy in acute ischemic stroke. Further studies are needed to confirm our findings. Copyright © 2017. Published by Elsevier Inc.

  20. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ying-bo Li

    2015-01-01

    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  1. Impact of remote ischemic preconditioning on wound healing in small bowel anastomoses

    Science.gov (United States)

    Holzner, Philipp Anton; Kulemann, Birte; Kuesters, Simon; Timme, Sylvia; Hoeppner, Jens; Hopt, Ulrich Theodor; Marjanovic, Goran

    2011-01-01

    AIM: To investigate the influence of remote ischemic preconditioning (RIPC) on anastomotic integrity. METHODS: Sixty male Wistar rats were randomized to six groups. The control group (n = 10) had an end-to-end ileal anastomosis without RIPC. The preconditioned groups (n = 34) varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis (n = 9). On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosal ischemic injury were collected. The data are given as median (range). RESULTS: On postoperative day 4, median bursting pressure was 124 mmHg (60-146 mmHg) in the control group. The experimental groups did not show a statistically significant difference (P > 0.05). Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION: RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning. PMID:21455330

  2. 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)

  3. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

    Science.gov (United States)

    Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

    2016-01-01

    Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

  4. The Ubiquitin E3 Ligase TRAF6 Exacerbates Ischemic Stroke by Ubiquitinating and Activating Rac1.

    Science.gov (United States)

    Li, Tao; Qin, Juan-Juan; Yang, Xia; Ji, Yan-Xiao; Guo, Fangliang; Cheng, Wen-Lin; Wu, Xiaolin; Gong, Fu-Han; Hong, Ying; Zhu, Xue-Yong; Gong, Jun; Wang, Zhihua; Huang, Zan; She, Zhi-Gang; Li, Hongliang

    2017-12-13

    Stroke is one of the leading causes of morbidity and mortality worldwide. Inflammation, oxidative stress, apoptosis, and excitotoxicity contribute to neuronal death during ischemic stroke; however, the mechanisms underlying these complicated pathophysiological processes remain to be fully elucidated. Here, we found that the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) was markedly increased after cerebral ischemia/reperfusion (I/R) in mice. TRAF6 ablation in male mice decreased the infarct volume and neurological deficit scores and decreased proinflammatory signaling, oxidative stress, and neuronal death after cerebral I/R, whereas transgenic overexpression of TRAF6 in male mice exhibited the opposite effects. Mechanistically, we demonstrated that TRAF6 induced Rac1 activation and consequently promoted I/R injury by directly binding and ubiquitinating Rac1. Either functionally mutating the TRAF6 ubiquitination site on Rac1 or inactivating Rac1 with a specific inhibitor reversed the deleterious effects of TRAF6 overexpression during I/R injury. In conclusion, our study demonstrated that TRAF6 is a key promoter of ischemic signaling cascades and neuronal death after cerebral I/R injury. Therefore, the TRAF6/Rac1 pathway might be a promising target to attenuate cerebral I/R injury. SIGNIFICANCE STATEMENT Stroke is one of the most severe and devastating neurological diseases globally. The complicated pathophysiological processes restrict the translation of potential therapeutic targets into medicine. Further elucidating the molecular mechanisms underlying cerebral ischemia/reperfusion injury may open a new window for pharmacological interventions to promote recovery from stroke. Our study revealed that ischemia-induced tumor necrosis factor receptor-associated factor 6 (TRAF6) upregulation binds and ubiquitinates Rac1 directly, which promotes neuron death through neuroinflammation and neuro-oxidative signals. Therefore, precisely targeting

  5. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

    Science.gov (United States)

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-07-31

    Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

  6. 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.

  7. 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.

  8. 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.

  9. [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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. 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.

  19. Effects of Fluoxetine on Neural Functional Prognosis after Ischemic Stroke: A Randomized Controlled Study in China.

    Science.gov (United States)

    He, Yi-Tao; Tang, Bing-Shan; Cai, Zhi-Li; Zeng, Si-Ling; Jiang, Xin; Guo, Yi

    2016-04-01

    We investigated the effects of fluoxetine on the short-term and long-term neural functional prognoses after ischemic stroke. In this prospective randomized controlled single-blind clinical study in China, eligible patients afflicted with ischemic stroke were randomized into control and treatment groups. Patients in the treatment group received fluoxetine in addition to the basic therapies in the control group over a period of 90 days. The follow-up period was 180 days. We evaluated the effects of fluoxetine on the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score after ischemic stroke through single- and multiple-factor analysis. The mean NIHSS score on day 180 after treatment was significantly lower in the treatment group than in the control group (P = .009). The mean BI scores on days 90 and 180 were significantly higher in the treatment group (P = .026) than in the control group (P = .011). The improvements in the NIHSS and BI scores on days 90 and 180 compared with baseline in the treatment group were all significantly greater than that in the control group (P = .033, P = .013, P = .013, P = .019, respectively). Treatment with fluoxetine was an independent factor affecting the NIHSS and BI scores on day 180 after treatment. Treatment with fluoxetine for 90 days after ischemic stroke can improve the long-term neural functional outcomes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Nationwide Estimates of 30-Day Readmission in Patients With Ischemic Stroke.

    Science.gov (United States)

    Vahidy, Farhaan S; Donnelly, John P; McCullough, Louise D; Tyson, Jon E; Miller, Charles C; Boehme, Amelia K; Savitz, Sean I; Albright, Karen C

    2017-05-01

    Readmission within 30 days of hospital discharge for ischemic stroke is an important quality of care metric. We aimed to provide nationwide estimates of 30-day readmission in the United States, describe important reasons for readmission, and sought to explore factors associated with 30-day readmission, particularly the association with recanalization therapy. We conducted a weighted analysis of the 2013 Nationwide Readmission Database to represent all US hospitalizations. Adult patients with acute ischemic stroke including those who received intravenous tissue-type plasminogen activator and intra-arterial therapy were identified using International Classification of Diseases -Ninth Revision codes. Readmissions were defined as any readmission during the 30-day post-index hospitalization discharge period for the eligible patient population. Proportions and 95% confidence intervals for overall 30-day readmissions and for unplanned and potentially preventable readmissions are reported. Survey design logistic regression models were fit for determining crude and adjusted odds ratios and 95% confidence interval for association between recanalization therapy and 30-day readmission. Of the 319 317 patients with acute ischemic stroke, 12.1% (95% confidence interval, 11.9-12.3) were readmitted. Of these, 89.6% were unplanned and 12.9% were potentially preventable. More than 20% of all readmissions were attributable to acute cerebrovascular disease. Readmitted patients were older and had a higher comorbidity burden. After controlling for age, sex, insurance status, and comorbidities, patients who underwent recanalization therapy had significantly lower odds of 30-day readmission (odds ratio, 0.82; 95% confidence interval, 0.77-0.89). Up to 12% of patients with ischemic stroke get readmitted within 30 days post-discharge period, and recanalization therapy is associated with 11% to 23% lower odds of 30-day readmission. © 2017 American Heart Association, Inc.

  1. Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

    Science.gov (United States)

    He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

    2018-06-01

    We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

  2. Use of APACHE II and SAPS II to predict mortality for hemorrhagic and ischemic stroke patients.

    Science.gov (United States)

    Moon, Byeong Hoo; Park, Sang Kyu; Jang, Dong Kyu; Jang, Kyoung Sool; Kim, Jong Tae; Han, Yong Min

    2015-01-01

    We studied the applicability of the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in patients admitted to the intensive care unit (ICU) with acute stroke and compared the results with the Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS). We also conducted a comparative study of accuracy for predicting hemorrhagic and ischemic stroke mortality. Between January 2011 and December 2012, ischemic or hemorrhagic stroke patients admitted to the ICU were included in the study. APACHE II and SAPS II-predicted mortalities were compared using a calibration curve, the Hosmer-Lemeshow goodness-of-fit test, and the receiver operating characteristic (ROC) curve, and the results were compared with the GCS and NIHSS. Overall 498 patients were included in this study. The observed mortality was 26.3%, whereas APACHE II and SAPS II-predicted mortalities were 35.12% and 35.34%, respectively. The mean GCS and NIHSS scores were 9.43 and 21.63, respectively. The calibration curve was close to the line of perfect prediction. The ROC curve showed a slightly better prediction of mortality for APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients. The GCS and NIHSS were inferior in predicting mortality in both patient groups. Although both the APACHE II and SAPS II systems can be used to measure performance in the neurosurgical ICU setting, the accuracy of APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients was superior. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  4. Photoacoustic imaging for assessing ischemic kidney damage in vivo

    Science.gov (United States)

    Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

    2018-02-01

    Ischemic reperfusion injuries (IRIs) occur after blood returns to a tissue or organ after a period without oxygen or nutrients, which causes an inflammatory response leading to heterogeneous scarring of the nearby tissue and vasculature. This is associated with long-term decreases blood flow, and necrosis. Although most commonly associated with heart attacks and strokes, IRIs are also a side effect of organ transplants, when the organ is reperfused in the recipient's body after being transported from the donor to the transplant hospital. Currently, the optimal method of monitoring for IRI is limited to biopsies, which are invasive and poorly monitor the spatial heterogeneity of the damage. To non-invasively identify changes in kidneys, the left renal artery in mice (n=3) was clamped for 45 minutes to create an IRI event. Both kidneys of each animal were monitored using photoacoustics (PA) with the VevoLAZR system (Fujifilm-VisualSonics, Toronto) three, four and eight weeks after surgery. IRI-treated kidneys show increased picosirius red staining, indicative of collagen (0.601 vs 0.042, p < 0.0001), decreased size as assessed by cross-sectional area (7.8 mm2 vs 35.9 mm2 , p < 0.0001), and decreased oxygen saturation (sO2; 62% vs 77%, p = 0.02). Analysis of the photoacoustic data shows that a two-point metric, the 715:930 nm ratio of the whole kidney (1.05 vs 0.57, p = 0.049) and the optical spectral slope (OSS) (0.8 * 10-3 vs 3.0 * 10-3, p = 0.013) are both able to differentiate between IRI-treated and healthy kidneys. These data suggest that photoacoustics can be used as a non-invasive method to observe in vivo changes in the kidney due to IRI.

  5. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

    OpenAIRE

    Lou Yongli; Guo Dewei; Zhang Hui; Song Laijun

    2016-01-01

    In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs) cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI) brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were adminis...

  6. Modelling Ischemic Stroke and Temperature Intervention Using Vascular Porous Method

    Science.gov (United States)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2017-11-01

    In the event of cerebral infarction, a region of tissue is supplied with insufficient blood flow to support normal metabolism. This can lead to an ischemic reaction which incurs cell death. Through a reduction of temperature, the metabolic demand can be reduced, which then offsets the onset of necrosis. This allows extra time for the patient to receive medical attention and could help prevent permanent brain damage from occurring. Here, we present a vascular-porous (VaPor) blood flow model that can simulate such an event. Cerebral blood flow is simulated using a combination of 1-Dimensional vessels embedded in 3-Dimensional porous media. This allows for simple manipulation of the structure and determining the effect of an obstructed vessel. Results show regional temperature increase of 1-1.5°C comparable with results from literature (in contrast to previous simpler models). Additionally, the application of scalp cooling in such an event dramatically reduces the temperature in the affected region to near hypothermic temperatures, which points to a potential rapid form of first intervention.

  7. Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Kengo Furuichi

    2012-02-01

    Full Text Available Background/Aim: Fas ligand (FasL and tumor necrosis factor (TNF-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification. Methods: We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1-deficient mice. Results: TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.

  8. Effect of using fluoxetine at different time windows on neurological functional prognosis after ischemic stroke.

    Science.gov (United States)

    Guo, Yi; He, Yitao; Tang, Bingshan; Ma, Kefu; Cai, Zhili; Zeng, Siling; Zhang, Ying; Jiang, Xin

    2016-01-01

    To evaluate the effect of using fluoxetine at different time intervals after ischemic stroke on neurological functional prognosis in China. The patients enrolled were randomly allocated to three groups. Group A received fluoxetine 20 mg/day immediately; group B received fluoxetine 20 mg/day 7 days after enrollment; and group C did not receive fluoxetine. The therapeutic duration of fluoxetine was 90 days and the follow-up period was 180 days. The mean NIHSS score at day 90 was significantly lower in group A than group C (P = 0.005), while at day 180, the mean score in group A was significantly lower than groups B and C (P = 0.035, P = 0.000), respectively. The mean BI score at day 90 was significantly higher in group A than group C (P = 0.001), while at day 180, the mean score in group A was significantly higher than groups B and C (P = 0.036, P = 0.000), respectively. Regression analysis indicated that lower NIHSS score and higher BI score at day 180 were attributed to the early administration of fluoxetine. In patients with ischemic stroke, early administration of fluoxetine may improve the neurological functional prognosis.

  9. Digital Receiver Phase Meter

    Science.gov (United States)

    Marcin, Martin; Abramovici, Alexander

    2008-01-01

    The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

  10. 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

  11. Risk score to predict gastrointestinal bleeding after acute ischemic stroke.

    Science.gov (United States)

    Ji, Ruijun; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Singhal, Aneesh B; Wang, Yongjun

    2014-07-25

    Gastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke. The AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and β-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. A total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts

  12. 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.

  13. 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.

  14. 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)

  15. 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

  16. 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.

  17. 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.)

  18. 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

  19. 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.

  20. 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.

  1. Prophylactic antibiotic treatment in severe acute ischemic stroke: the Antimicrobial chemopRrophylaxis for Ischemic STrokE In MaceDonIa-Thrace Study (ARISTEIDIS).

    Science.gov (United States)

    Tziomalos, Konstantinos; Ntaios, George; Miyakis, Spiros; Papanas, Nikolaos; Xanthis, Andreas; Agapakis, Dimitrios; Milionis, Haralampos; Savopoulos, Christos; Maltezos, Efstratios; Hatzitolios, Apostolos I

    2016-10-01

    Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p antibiotic treatment (RR 5.84, 95 % CI 2.03-16.79, p antibiotic treatment did not differ between patients who died during hospitalization and those discharged, or between patients who died during hospitalization or during follow-up and those who were alive 3 months after discharge. Prophylactic administration of antibiotics in patients with severe acute ischemic stroke is associated with an increased risk of infection during hospitalization, and does not affect short-term mortality risk.

  2. 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...

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. [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.

  8. 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.)

  9. The effects of pain sensitivity behaviour on Swiss White Mice ...

    African Journals Online (AJOL)

    This study evaluates the effects of Chloroquine phosphate on pain sensation in mice considering the fact that Chloroquine as s chemotherapic agent is known for its neurotoxicity effect. The mice were divided into three groups of 10 mice each. While group 1 as the control, 2 and 3 as the test groups and group 1 received ...

  10. 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

  11. Protective effects of ischemic postconditioning on intestinal

    Directory of Open Access Journals (Sweden)

    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

  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. Pressure difference receiving ears

    DEFF Research Database (Denmark)

    Michelsen, Axel; Larsen, Ole Næsbye

    2007-01-01

    Directional sound receivers are useful for locating sound sources, and they can also partly compensate for the signal degradations caused by noise and reverberations. Ears may become inherently directional if sound can reach both surfaces of the eardrum. Attempts to understand the physics...... of the eardrum. The mere existence of sound transmission to the inner surface does not ensure a useful directional hearing, since a proper amplitude and phase relationship must exist between the sounds acting on the two surfaces of the eardrum. The gain of the sound pathway must match the amplitude and phase...... of the sounds at the outer surfaces of the eardrums, which are determined by diffraction and by the arrival time of the sound, that is by the size and shape of the animal and by the frequency of sound. Many users of hearing aids do not obtain a satisfactory improvement of their ability to localize sound sources...

  15. Solar thermal energy receiver

    Science.gov (United States)

    Baker, Karl W. (Inventor); Dustin, Miles O. (Inventor)

    1992-01-01

    A plurality of heat pipes in a shell receive concentrated solar energy and transfer the energy to a heat activated system. To provide for even distribution of the energy despite uneven impingement of solar energy on the heat pipes, absence of solar energy at times, or failure of one or more of the heat pipes, energy storage means are disposed on the heat pipes which extend through a heat pipe thermal coupling means into the heat activated device. To enhance energy transfer to the heat activated device, the heat pipe coupling cavity means may be provided with extensions into the device. For use with a Stirling engine having passages for working gas, heat transfer members may be positioned to contact the gas and the heat pipes. The shell may be divided into sections by transverse walls. To prevent cavity working fluid from collecting in the extensions, a porous body is positioned in the cavity.

  16. 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.

  17. 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.

  18. 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.

  19. Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

    Science.gov (United States)

    Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

    2015-07-01

    Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. © 2015 American Heart Association, Inc.

  20. 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.

  1. Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

    Science.gov (United States)

    Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

    2013-06-21

    We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

  2. Docetaxel chronopharmacology in mice.

    Science.gov (United States)

    Tampellini, M; Filipski, E; Liu, X H; Lemaigre, G; Li, X M; Vrignaud, P; François, E; Bissery, M C; Lévi, F

    1998-09-01

    Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administration of docetaxel. In experiment (Exp) 1, the drug was given once a week (wk) for 6 wks (20 mg/kg/wk) or for 5 wks (30 mg/kg/wk) at one of six circadian times, during light when mice were resting [3, 7, or 11 hours after light onset (HALO)], or during darkness, when mice were active (15, 19, or 23 HALO). Endpoints were survival and body weight change. In Exp 2 and 3, docetaxel (30 mg/kg/wk) was administered twice, 1 wk apart, at one of four circadian stages (7, 11, 19, or 23 HALO). Endpoints were hematological and intestinal toxicities. In Exp 4, circadian changes in cell cycle phase distribution and BCL-2 immunofluorescence were investigated in bone marrow as possible mechanisms of docetaxel tolerability rhythm. In Exp 5 to 7, docetaxel was administered to mice bearing measurable P03 pancreatic adenocarcinoma (270-370 mg), with tumor weight and survival as endpoints. Mice from Exp 5 and 6 received a weekly schedule of docetaxel at one of six circadian stages (20 or 30 mg/kg/wk at 3, 7, 11, 15, 19, or 23 HALO). In Exp 7, docetaxel (30 mg/kg) was given every 2 days (day 1, 3, 5 schedule) at 7, 11, 19, or 23 HALO. Docetaxel dosing in the second half of darkness (19 or 23 HALO) resulted in significantly worse toxicity than its administration during the light span (3, 7, or 11 HALO). The survival rate ranged from 56.3% in the mice treated at 23 HALO to 93.8 or 87.5% in those injected at 3 or 11 HALO, respectively (Exp 1, P active at 11 HALO (percentage increase in life span, 390%) and least active at 23 HALO (210%). Docetaxel tolerability and antitumor efficacy were simultaneously enhanced by drug dosing in the light span, when mice were resting. Mechanisms

  3. Ischemic Stroke with Cardiac Pacemaker Implantation: Comparison of Physiological and Ventricular Pacing Modes.

    Science.gov (United States)

    Kato, Yuji; Hayashi, Takeshi; Kato, Ritsushi; Tanahashi, Norio; Takao, Masaki

    2017-09-01

    The clinical characteristics of ischemic stroke in patients with a pacemaker (PM) are not well understood. Forty-six ischemic stroke patients with a PM were investigated retrospectively, and the impact of different pacing modes was compared. The patients were divided into a physiological pacing group (n = 22) and a ventricular pacing group (n = 24). The prevalence of atrial fibrillation (AF) was significantly higher in the ventricular pacing group (36% versus 75%; P = .008). The mean left atrial dimension was relatively large in the ventricular pacing group than in the physiological pacing group (44.5 ± 6.7 mm versus 39.1 ± 8.5 mm, respectively; P = .071). Twenty-four percent of the patients were receiving anticoagulants, whereas 41% of the patients were receiving antiplatelet drugs. Cardioembolism was the most common stroke subtype in both groups. Although there was no statistically significant difference, neurological severity on admission was higher in the ventricular pacing group than in the physiological pacing group (P = .061). Functional outcomes, excluding patients with transient ischemic attack or prior stroke, significantly declined in the ventricular pacing group compared with the physiological pacing group (P = .044). The avoidance of the ventricular pacing mode may result in improved clinical outcomes. In patients without persistent AF, it may be important to select physiological pacing instead of ventricular pacing to decrease potential stroke severity. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. Haematopoietic stem cell migration to the ischemic damaged kidney is not altered by manipulating the SDF-1/CXCR4-axis

    NARCIS (Netherlands)

    Stroo, Ingrid; Stokman, Geurt; Teske, Gwendoline J. D.; Florquin, Sandrine; Leemans, Jaklien C.

    2009-01-01

    Methods. HSC were isolated from mouse bone marrow and labelled with a cell tracker. Acceptor mice were subjected to unilateral ischemia and received HSC intravenously directly after reperfusion. In addition, in separate groups of acceptor mice, endogenous SDF-1 or HSC-associated CXCR4 was blocked or

  5. 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...

  6. Hepatic branch vagus nerve plays a critical role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

    Directory of Open Access Journals (Sweden)

    Shinichi Harada

    Full Text Available Orexin-A (a neuropeptide in the hypothalamus plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve with orexin-1 receptor and c-Fos (activated neural cells marker. These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

  7. Hepatic Branch Vagus Nerve Plays a Critical Role in the Recovery of Post-Ischemic Glucose Intolerance and Mediates a Neuroprotective Effect by Hypothalamic Orexin-A

    Science.gov (United States)

    Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

    2014-01-01

    Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A. PMID:24759941

  8. 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.

  9. Use of a Diagnostic Score to Prioritize Computed Tomographic (CT Imaging for Patients Suspected of Ischemic Stroke Who May Benefit from Thrombolytic Therapy.

    Directory of Open Access Journals (Sweden)

    Wen Yea Hwong

    Full Text Available A shortage of computed tomographic (CT machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging.From the Malaysian National Neurology Registry, we selected patients aged 18 years and over with clinical features suggesting of a stroke, who arrived in the hospital 4.5 hours or less from ictus. The prioritization of receiving CT imaging was left to the discretion of the treating physician. We applied the Siriraj Stroke Score to all patients, refitted the score and defined a cut-off value to best distinguish an ischemic stroke from a hemorrhagic stroke.Of the 2176 patients included, 73% had an ischemic stroke. Only 33% of the ischemic stroke patients had CT imaging within 4.5 hours. The median door-to-scan time for these patients was 4 hours (IQR: 1;16. With the recalibrated score, it would have been possible to prioritize 95% (95% CI: 94%-96% of patients with an ischemic stroke for urgent CT imaging.In settings where CT imaging capacity is limited, we propose the use of the Siriraj Stroke Score to prioritize patients with a probable ischemic stroke for urgent CT imaging.

  10. CERN apprentice receives award

    CERN Multimedia

    2008-01-01

    Another CERN apprentice has received an award for the quality of his work. Stéphane Küng (centre), at the UIG ceremony last November, presided over by Geneva State Councillor Pierre-François Unger, Head of the Department of Economics and Health. Electronics technician Stéphane Küng was honoured in November by the Social Foundation of the Union Industrielle Genevoise (UIG) as one of Geneva’s eight best apprentices in the field of mechatronics. The 20-year-old Genevan obtained his Federal apprentice’s certificate (Certificat fédéral de capacité - CFC) in June 2007, achieving excellent marks in his written tests at the Centre d’Enseignement Professionnel Technique et Artisanal (CEPTA). Like more than 200 youngsters before him, Stéphane Küng spent part of his four-year sandwich course working at CERN, where he followed many practical training courses and gained valuable hands-on experience in various technical groups and labs. "It’ always very gr...

  11. Post-ischemic stroke rehabilitation is associated with a higher risk of fractures in older women: A population-based cohort study.

    Science.gov (United States)

    Huang, Huei Kai; Lin, Shu Man; Yang, Clement Shih Hsien; Liang, Chung Chao; Cheng, Hung Yu

    2017-01-01

    Rehabilitation can improve physical activity after stroke. However, patients may be more prone to falls and fractures because of balance and gait deficits. Few reports have studied the relationship between rehabilitation and subsequent fractures after ischemic stroke. To investigate whether post-stroke rehabilitation affects fracture risk. We conducted a population-based retrospective cohort study based on the Taiwan National Health Insurance Research Database. Patients with a newly diagnosed ischemic stroke between 2000 and 2012 were included. After propensity score matching, a total of 8,384 patients were enrolled. Half of the patients (4,192) received post-stroke rehabilitation within 1 month; the other half did not receive any post-stroke rehabilitation. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) for fractures among patients with and without rehabilitation within 1 year after ischemic stroke. Patients were further stratified by sex and age (20-64 and ≥65 years). Patients receiving post-stroke rehabilitation had a higher incidence of fracture (6.2 per 100 person-years) than those who did not (4.1 per 100 person-years) after adjustment for sociodemographic and coexisting medical conditions [HR = 1.53, 95% confidence interval (CI) = 1.25-1.87, p rehabilitation had a significantly higher risk of fracture (HR = 1.62, 95% CI = 1.21-2.17, p = 0.001). Rehabilitation after ischemic stroke is associated with an increased fracture risk in older women.

  12. 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

  13. [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.

  14. 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.

  15. 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 ...

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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

  6. 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....

  7. Immediate effects of hamstring stretching alone or combined with ischemic compression of the masseter muscle on hamstrings extensibility, active mouth opening and pain in athletes with temporomandibular dysfunction.

    Science.gov (United States)

    Espejo-Antúnez, Luis; Castro-Valenzuela, Elisa; Ribeiro, Fernando; Albornoz-Cabello, Manuel; Silva, Anabela; Rodríguez-Mansilla, Juan

    2016-07-01

    To assess the immediate effects of hamstrings stretching alone or combined with ischemic compression of the masseter muscle on hamstrings extensibility, active mouth opening and pain in athletes with temporomandibular dysfunction and hamstrings shortening. Forty-two participants were randomized to receive the stretching technique (n = 21) or the stretching plus the ischemic compression (n = 21). Outcome measures were: hamstrings extensibility, active mouth opening, pressure pain thresholds and pain intensity. Both interventions improved significantly active mouth opening (group 1: 35.7 ± 6.7 to 39.1 ± 7.6 mm, p Hamstrings stretching induced an acute improvement in hamstrings extensibility, active mouth opening and pain. Moreover, the addition of ischemic compression did not induce further improvements on the assessed parameters. Copyright © 2016. Published by Elsevier Ltd.

  8. Predicting functional outcomes of posterior circulation acute ischemic stroke in first 36 h of stroke onset.

    Science.gov (United States)

    Lin, Sheng-Feng; Chen, Chin-I; Hu, Han-Hwa; Bai, Chyi-Huey

    2018-04-01

    Posterior circulation acute ischemic stroke constitutes one-fourth of all ischemic strokes and can be efficiently quantified using the posterior circulation Alberta stroke program early computed tomography score (PC-ASPECTS) through diffusion-weighted imaging. We investigated whether the PC-ASPECTS and National Institutes of Health Stroke Scale (NIHSS) facilitate functional outcome prediction among Chinese patients with posterior circulation acute ischemic stroke. Participants were selected from our prospective stroke registry from January 1, 2015, to December 31, 2016. The baseline NIHSS score was assessed on the first day of admission, and brain magnetic resonance imaging was performed within 36 h after stroke onset. Simple and multiple logistic regressions were conducted to determine stroke risk factors and the PC-ASPECTS. Receiver operating characteristics (ROC) curve analysis was performed to compare the NIHSS and PC-ASPECTS. Of 549 patients from our prospective stroke admission registry database, 125 (22.8%) had a diagnosis of posterior circulation acute ischemic stroke. The optimal cutoff for the PC-ASPECTS in predicting outcomes was 7. The odds ratios of the PC-ASPECTS (≤ 7 vs > 7) in predicting outcomes were 6.33 (p = 0.0002) and 8.49 (p = 0.0060) in the univariate and multivariate models, respectively, and 7.52 (p = 0.0041) in the aging group. On ROC curve analysis, the PC-ASPECTS demonstrated more reliability than the baseline NIHSS for predicting functional outcomes of minor posterior circulation stroke. In conclusion, both the PC-ASPECTS and NIHSS help clinicians predict functional outcomes. PC-ASPECTS > 7 is a helpful discriminator for achieving favorable functional outcome prediction in posterior circulation acute ischemic stroke.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. Influence of risk area size and location on native collateral resistance and ischemic zone perfusion

    International Nuclear Information System (INIS)

    Gumm, D.C.; Cooper, S.M.; Thompson, S.B.; Marcus, M.L.; Harrison, D.C.

    1988-01-01

    To examine the effect of risk area size on collateral resistance and ichemic region perfusion, the authors produced different sized risk areas by occluding either the left anterior descending (LAD) or the circumflex (Cx) coronary artery at different sites. The most proximal occlusion of the LAD and Cx produced risk areas of 43 ± 5 and 36 ± 2% of left ventricular (LV) mass, respectively, whereas distal LAD and Cx occlusions produced risk areas of 13 ± 2 and 17 ± 2% of LV weight, respectively. Although total collateral flow was highest to the largest risk areas, collateral flow per 100 g of ischemic myocardium was 80% higher to the small LAD risk area compared with the large LAD risk area and 43% higher to the small Cx risk area compared with the large Cx risk area. Collateral resistance, calculated from the transcollateral pressure and perfusion per 100 g of myocardium was significantly lower in the small risk areas than in the large ones. They examined the effect of risk area location on collateral perfusion and resistance. These experiments show that collateral resistance is influenced both by ischemic region size and location. Small risk areas receive more collateral flow per mass of tissue than large risk areas, and apical risk areas receive greater quantities of collateral flow than those located at the base. These data may explain why small risk areas often do not develop infarction after coronary occlusion

  18. 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

  19. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine Treatment

    Directory of Open Access Journals (Sweden)

    Sriranjini Sitaram Jaideep

    2014-01-01

    Full Text Available Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory (mean age 39.26 ± 9.88 years; male 43, female 7 were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I or Ayurveda treatment (Group II for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS. Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F=8.16, P=0.007, F=9.73, P=0.004, F=13.51, and P=0.001, resp.. The BRS too increased following the treatment period (F=10.129, P=0.004. Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted.

  20. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. I. Petrov

    2015-09-01

    Full Text Available Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р<0.0001 and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58% among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028.Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.

  1. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. I. Petrov

    2013-01-01

    Full Text Available Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р<0.0001 and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58% among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028.Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.

  2. Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.

    Science.gov (United States)

    Lee, Soo Vin; Choi, Kyung Ha; Choi, Young Whan; Hong, Jin Woo; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-04-01

    Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral

  3. 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.

  4. 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.

  5. Transient Ischemic Attack Caused by Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    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

  6. Hepatitis isquémica Ischemic hepatitis

    Directory of Open Access Journals (Sweden)

    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

  7. 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

    The prognosis of patients with coronary artery disease (CAD) at hospital discharge was constantly varying, and post-discharge risk of ischemic events remain a concern. However, risk prediction tools to identify risk of ischemia for these patients has not yet been reported. We sought to develop a scoring system for predicting long-term ischemic events in CAD patients receiving antiplatelet therapy that would be beneficial in appropriate personalized decision-making for these patients. In this prospective Optimal antiPlatelet Therapy for Chinese patients with Coronary Artery Disease (OPT-CAD, NCT01735305) registry, a total of 14,032 patients with CAD receiving at least one kind of antiplatelet agent were enrolled from 107 centers across China, from January 2012 to March 2014. The risk scoring system was developed in a derivation cohort (enrolled initially 10,000 patients in the database) using a logistic regression model and was subsequently tested in a validation cohort (the last 4,032 patients). Points in risk score was assigned based on the multivariable odds ratio of each factor. Ischemic events were defined as the composite of cardiac death, myocardial infarction or stroke. Ischemic events occurred in 342 (3.4%) patients in the derivation cohort and 160 (4.0%) patients in the validation cohort during 1-year follow-up. The OPT-CAD score, ranging from 0-257 points, consist of 10 independent risk factors, including age (0-71 points), heart rates (0-36 points), hypertension (0-20 points), prior myocardial infarction (16 points), prior stroke (16 points), renal insufficient (21 points), anemia (19 points), low ejection fraction (22 points), positive cardiac troponin (23 points) and ST-segment deviation (13 points). In predicting 1-year ischemic events, the area under receiver operating characteristics curve were 0.73 and 0.72 in derivation and validation cohort, respectively. The incidences of ischemic events in low- (0-90 points), medium- (91-150 points) and

  8. GNSS Software Receiver for UAVs

    DEFF Research Database (Denmark)

    Olesen, Daniel Madelung; Jakobsen, Jakob; von Benzon, Hans-Henrik

    2016-01-01

    This paper describes the current activities of GPS/GNSS Software receiver development at DTU Space. GNSS Software receivers have received a great deal of attention in the last two decades and numerous implementations have already been presented. DTU Space has just recently started development of ...... of our own GNSS software-receiver targeted for mini UAV applications, and we will in in this paper present our current progress and briefly discuss the benefits of Software Receivers in relation to our research interests....

  9. Effects of Momordica charantia (Bitter Melon on Ischemic Diabetic Myocardium

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    Attila Czompa

    2017-03-01

    Full Text Available Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM extract suspended in mucin–water vehicle, or with vehicle (Control. Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO and treatment (Control or BM. Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in

  10. Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium.

    Science.gov (United States)

    Czompa, Attila; Gyongyosi, Alexandra; Szoke, Kitti; Bak, Istvan; Csepanyi, Evelin; Haines, David D; Tosaki, Arpad; Lekli, Istvan

    2017-03-20

    Objective : A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods : Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results : Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO

  11. Effects of edaravone on early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator.

    Science.gov (United States)

    Wada, Tomoki; Yasunaga, Hideo; Inokuchi, Ryota; Horiguchi, Hiromasa; Fushimi, Kiyohide; Matsubara, Takehiro; Nakajima, Susumu; Yahagi, Naoki

    2014-10-15

    We investigated whether edaravone could improve early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator (rtPA). We conducted a retrospective cohort study using the Japanese Diagnosis Procedure Combination database. We identified patients admitted with a primary diagnosis of ischemic stroke from 1 July 2010 to 31 March 2012 and treated with rtPA on the same day of stroke onset or the following day. Thereafter, we selected those who received edaravone on the same day of rtPA administration (edaravone group), and those who received rtPA without edaravone (control group). The primary outcomes were modified Rankin Scale (mRS) scores at discharge. One-to-one propensity-score matching was performed between the edaravone and control groups. An ordinal logistic regression analysis for mRS scores at discharge was performed with adjustment for possible variables as well as clustering of patients within hospitals using a generalized estimating equation. We identified 6336 eligible patients for inclusion in the edaravone group (n=5979; 94%) and the control group (n=357; 6%) as the total population. In 356 pairs of the propensity-matched population, the ordinal logistic regression analysis showed that edaravone was significantly associated with lower mRS scores of patients at discharge (adjusted odds ratio: 0.74; 95% confidence interval: 0.57-0.96). Edaravone may improve early outcomes in acute ischemic stroke patients treated with rtPA. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Evaluation of regenerative capacity after kidney ischemic/reperfustion injury using 99mTc-DMSA

    International Nuclear Information System (INIS)

    Kwak, W. J.; Kim, J. W.; Park, K. M.; Lee, S. W.; Ahn, B. C.; Lee, J. T.; Yoo, J. S.

    2007-01-01

    Acute renal failure can be caused by a reduced renal blood flow induced because of ischemic injury. The damaged kidney can be completely restored in structure and function. 99m Tc-DMSA binds to cortical tubules in kidney and its uptake has been suggested to indicate function of cortical mass. Herein, the generative capacity of kidney after bilateral or unilateral ischemia/reperfusion (I/R) injury was evaluated non-invasively by scintigraphic imaging. Three different animal models were used. One or both kidneys of mice were subjected ischemic for 30 min for unilateral or bilateral I/R model, respectively. In third model, one kidney was excised and the other kidney was subjected ischemic for 30 min to give nephrectomy model. At 1 hr, 1 d, 3 d, 1 w, 2 w, 3 w after reperfusion, 99m Tc-DMSA (27.7 MBq) was injected via tail vein. After 3 hr, the mice were scanned for 30 min with pinhole equipped gamma camera. The ratio of ROI counts of kidney to total counts was calculated. In unilateral I/R mouse, the 99m Tc-DMSA uptake of injured kidney was decreased continuously up to 3 w (13.9 to 7.7%), while uptake in normal kidney is slowly increased. In case of nephrectomy model, 99m Tc-DMSA uptake of injured kidney was rapidly restored within 1 w after I/R operation (8.5 to 30%). Bilateral model showed reduced 99m Tc-DMSA uptake at 1 d, but total uptake in both I/R kidney was also increase up to 30% after 1 w and the uptake was maintained up to 3 w. In unilateral model, the 99m Tc-DMSA uptake of injured kidney kept decreasing up to 3 w while normal kidney showed increased 99m Tc-DMSA uptake. The restoration of I/R kidney was not observed within 3 w. However, in case of animal models which have only I/R kidneys such as bilateral and nephrectomy models, the 99m Tc-DMSA uptake was restored within 1 w and the excised kidney size was also normal in contrast to much smaller I/R kidney of unilateral model

  13. A Case of Recurrent Transient Monocular Visual Loss after Receiving Sildenafil

    Directory of Open Access Journals (Sweden)

    Asaad Ghanem Ghanem

    2011-01-01

    Full Text Available A 53-year-old man was attended to the Clinic Ophthalmic Center, Mansoura University, Egypt, with recurrent transient monocular visual loss after receiving sildenafil citrate (Viagra for erectile dysfunction. Examination for possible risk factors revealed mild hypercholesterolemia. Family history showed that his father had suffered from bilateral nonarteritic anterior ischemic optic neuropathy (NAION. Physicians might look for arteriosclerotic risk factors and family history of NAION among predisposing risk factors before prescribing sildenafil erectile dysfunction drugs.

  14. 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)

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

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    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

  16. Computed tomography diagnosis of neonatal hypoxic ischemic encephalopathy combined with intracranial hemorrhage and clinical nursing treatment.

    Science.gov (United States)

    Zhang, Y; Zhang, J L; Li, Y

    2016-01-01

    Hypoxic ischemic encephalopathy (HIE), one of the common causes of newborn invalidism, is likely to induce nervous system-associated sequelae and even intracranial hemorrhage in severe cases. The incidence rate of HIE has been rising in recent years. In order to study the clinical nursing effect for HIE combined with intracranial hemorrhage, 76 newborns diagnosed with HIE combined with intracranial hemorrhage by spiral computed tomography (CT) from the of Binzhou People’s Hospital, Shandong, China were selected. They were divided into a control group and an intervention group. The control group received routine nursing, while the intervention group received comprehensive nursing intervention. The experimental results suggested that the mental developmental index (MDI) value and the psychomotor developmental index (PDI) value of patients in the intervention group were much higher than those of the control group and the difference was significant (phemorrhage recover more effectively, therefore is worth applying.

  17. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

    Science.gov (United States)

    Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

    2013-12-01

    Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. © 2013.

  18. Atrial fibrillation is a predictor of in-hospital mortality in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ong CT

    2016-06-01

    Full Text Available Cheung-Ter Ong,1,2 Yi-Sin Wong,3 Chi-Shun Wu,1 Yu-Hsiang Su1 1Department of Neurology, Chia-Yi Christian Hospital, 2Department of Nursing, Chung Jen Junior College of Nursing, Health Science and Management, Chiayi, 3Department of Family Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan, Republic of China Background/purpose: In-hospital mortality rate of acute ischemic stroke patients remains between 3% and 18%. For improving the quality of stroke care, we investigated the factors that contribute to the risk of in-hospital mortality in acute ischemic stroke patients.Materials and methods: Between January 1, 2007, and December 31, 2011, 2,556 acute ischemic stroke patients admitted to a stroke unit were included in this study. Factors such as demographic characteristics, clinical characteristics, comorbidities, and complications related to in-hospital mortality were assessed.Results: Of the 2,556 ischemic stroke patients, 157 received thrombolytic therapy. Eighty of the 2,556 patients (3.1% died during hospitalization. Of the 157 patients who received thrombolytic therapy, 14 (8.9% died during hospitalization. History of atrial fibrillation (AF, P<0.01 and stroke severity (P<0.01 were independent risk factors of in-hospital mortality. AF, stroke severity, cardioembolism stroke, and diabetes mellitus were independent risk factors of hemorrhagic transformation. Herniation and sepsis were the most common complications of stroke that were attributed to in-hospital mortality. Approximately 70% of in-hospital mortality was related to stroke severity (total middle cerebral artery occlusion with herniation, basilar artery occlusion, and hemorrhagic transformation. The other 30% of in-hospital mortality was related to sepsis, heart disease, and other complications.Conclusion: AF is associated with higher in-hospital mortality rate than in patients without AF. For improving outcome of stroke patients, we also need to focus to reduce serious neurological

  19. Association of Vagotomy and Decreased Risk of Subsequent Ischemic Stroke in Complicated Peptic Ulcer Patients: an Asian Population Study.

    Science.gov (United States)

    Fang, Chu-Wen; Tseng, Chun-Hung; Wu, Shih-Chi; Chen, William Tzu-Liang; Muo, Chih-Hsin

    2017-12-01

    The primary management of peptic ulcers is medical treatment. Persistent exacerbation of a peptic ulcer may lead to complications (perforation and/or bleeding). There has been a trend toward the use of a less invasive surgical simple suture, simple local suture or non-operative (endoscopic/angiography) hemostasis rather than acid-reducing vagotomy (i.e., vagus nerve severance) for treating complicated peptic ulcers. Other studies have shown the relationship between high vagus nerve activity and survival in cancer patients via reduced levels of inflammation, indicating the essential role of the vagus nerve. We were interested in the role of the vagus nerve and attempted to assess the long-term systemic effects after vagus nerve severance. Complicated peptic ulcer patients who underwent truncal vagotomy may represent an appropriate study population for investigating the association between vagus nerve severance and long-term effects. Therefore, we assessed the risks of subsequent ischemic stroke using different treatment methods in complicated peptic ulcer patients who underwent simple suture/hemostasis or truncal vagotomy/pyloroplasty. We selected 299,742 peptic ulcer patients without a history of stroke and Helicobacter pylori infection and an additional 299,742 matched controls without ulcer, stroke, and Helicobacter pylori infection from the National Health Insurance database. The controls were frequency matched for age, gender, Charlson comorbidity index (CCI) score, hypertension, hyperlipidemia history, and index year. Then, we measured the incidence of overall ischemic stroke in the two cohorts. The hazard ratio (HR) and the 95% confidence intervals (CIs) were estimated by Cox proportional hazard regression. Compared to the controls, peptic ulcer patients had a 1.86-fold higher risk of ischemic stroke. There were similar results in gender, age, CCI, hypertension, and hyperlipidemia stratified analyses. In complicated peptic ulcer patients, those who received

  20. Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study

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    Kawamura Ryoichi

    2009-11-01

    Full Text Available Abstract Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002 or ischemic stroke (p Conclusion Elevated serum resistin concentration appears to be an independent risk factor for ischemic stroke, especially lacunar and atherothrombotic infarction in the general Japanese population. The combination of high resistin and the presence of either diabetes or hypertension increased the risk of ischemic stroke.

  1. Posterior Ischemic Optic Neuropathy following Herpes Zoster Ophthalmicus

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    Mohammad Pakravan

    2009-01-01

    Full Text Available

    PURPOSE: To report a case of posterior ischemic optic neuropathy (PION following herpes zoster ophthalmicus (HZO. CASE REPORT: A 58-year-old woman with history of recent HZO in her right eye presented with acute painless loss of vision in the same eye to no light perception. Examination revealed a positive relative afferent pupillary defect and a normal appearing optic disc. Inflammatory and infiltrative lesions of the optic nerve were ruled out by laboratory and imaging studies. The patient received systemic acyclovir and prednisolone. Three months later, visual acuity improved to counting fingers, but the optic disc became pale and atrophic leading to a presumptive diagnosis of PION. Considering the positive PCR test for varicella zoster virus and the short time interval between the two presentations, HZO was considered as the most probable cause of the optic neuropathy. CONCLUSION: Herpes zoster ophthalmicus can be associated with PION.

  2. 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.

  3. Immunogenicity of a Psoralen-Inactivated Dengue Virus Type 1 Vaccine Candidate in Mice

    Science.gov (United States)

    2010-02-01

    United States Naval Medical Research Center Detachment, Lima, Peru , 1 and United States Naval Medical Research Center, Silver Spring, Maryland2 R...and 28. The mice in group B mice received 10-ng vaccine doses on study clays 0, 14, and 28. The mice in group C received 10-ng vaccine doses on

  4. 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.

  5. 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.)

  6. 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.)

  7. 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)

  8. 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)

  9. 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.

  10. The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment.

    Science.gov (United States)

    Gao, Ling; Zhao, Yi-Chao; Liang, Yan; Lin, Xian-Hua; Tan, Ya-Jing; Wu, Dan-Dan; Li, Xin-Zhu; Ye, Bo-Zhi; Kong, Fan-Qi; Sheng, Jian-Zhong; Huang, He-Feng

    2016-10-01

    Diabetic pregnancy, with ever increasing prevalence, adversely affects embryogenesis and increases vasculometabolic disorder risks in adult offspring. However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia/reperfusion (MIR), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria- and endoplasmic reticulum (ER) stress-mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (IRS)-1/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to MIR was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to MIR injury in their offspring, via restoring cardiac IRS-1/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented MIR injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Role of CT perfusion imaging in evaluating the effects of multiple burr hole surgery on adult ischemic Moyamoya disease

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Dong Wei; Zhao, Wen Yuan; Yang, Zhi Gang; Li, Qiang; Liu, Jian Min [Second Military Medical University, Department of Neurosurgery, Changhai Hospital, Shanghai (China); Zhang, Yong Wei [Second Military Medical University, Department of Neurology, Changhai Hospital, Shanghai (China); Xu, Bing; Ma, Xiao Long; Tian, Bing [Second Military Medical University, Department of Radiology, Changhai Hospital, Shanghai (China)

    2013-12-15

    To evaluate the effects of the multiple burr hole (MBH) revascularization on ischemic type adult Moyamoya disease (MMD) by computed tomography perfusion (CTP). Eighty-six ischemic MMD patients received CTP 1 week before and 3 weeks after MBH operation. Fifty-seven patients received it again at 6 month and underwent digital subtraction angiography (DSA) and mRS follow-up. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and relative values of ischemic symptomatic hemispheres were measured. Differences in pre- and post-surgery perfusion CT values were assessed. There were significant differences of CBF, TTP, and relative time to peak (rTTP) in ischemic hemisphere between 1 week before and 3 weeks after surgery, and no significant difference in relative cerebral blood flow (rCBF), CBV, relative cerebral blood volume (rCBV), MTT, relative mean transit time (rMTT). According to whether there was symptom improvement or not on 3 weeks after MBH, the rTTP value was not statistically significant in the patients whose symptoms were not improved at all on 3 weeks after operation. Six-month follow-up showed that CBF, rCBF, and rCBV values were significantly higher than those before operation. Postoperative MTT, TTP, rMTT, and rTTP values were significantly lower than those before operation. CTP is a sensitive method to obtain functional imaging of cerebral microcirculation, which can be a noninvasive assessment of the abnormalities of intracranial arteries and cerebral perfusion changes in MMD before and after surgery. CBF and TTP map, especially the relative values of TTP, seems to have the capability of being quite sensitive to the presence of altered brain perfusion at early time after indirect revascularization. (orig.)

  12. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    Science.gov (United States)

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

  13. Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke

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    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.)

  14. 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.)

  15. Clinical neurological characteristics of ischemic stroke subtypes in acute phase

    Directory of Open Access Journals (Sweden)

    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

  16. 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.

  17. 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.

  18. Significant interaction of hypertension and homocysteine on neurological severity in first-ever ischemic stroke patients.

    Science.gov (United States)

    Fan, Ying-Li; Zhan, Rui; Dong, Yi-Fei; Huang, Lei; Ji, Xi-Xin; Lu, Peng; Liu, Jian; Li, Ping; Cheng, Xiao-Shu

    2018-04-03

    It is not known whether combination of hypertension and high homocysteine (HHcy) impacts on stroke-related neurological severity. Our aim was to determine whether there is an interaction of hypertension and HHcy on neurological severity in first-ever ischemic stroke patients. We analyzed neurological severity among 189 consecutive first-ever ischemic stroke patients with or without hypertension or HHcy. Hypertension (odds ratio [OR]: 8.086, 95% confidence interval [CI]: 3.596-18.181, P < .001) and total homocysteine (OR: 1.403, 95% CI: 1.247-1.579, P < .001) were independently associated with neurological severity. In receiver-operating characteristic analysis, total homocysteine was a significant predictor of neurological severity (area under curve: 0.794; P < .001). A multiplicative interaction of hypertension and HHcy on more severe neurological severity was revealed by binary logistic regression (OR: 13.154, 95% CI: 5.293-32.691, P < .001). Analysis further identified a more than multiplicative interaction of hypertension and HHcy on neurological severity compared with patients without each condition (OR: 50.600, 95% CI: 14.775-173.285, P < .001). Interaction effect measured on an additive scale showed that 76.4% patients with moderate/severe neurological severity were attributed to interaction of hypertension and HHcy. Significant interaction of hypertension and HHcy on neurological severity was found on multiplicative and additive scale in first-ever Chinese ischemic stroke patients. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

  19. Cloning Mice.

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    Ogura, Atsuo

    2017-08-01

    Viable and fertile mice can be generated by somatic nuclear transfer into enucleated oocytes, presumably because the transplanted somatic cell genome becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring of mice were obtained by directly injecting donor nuclei into recipient enucleated oocytes. When this method is used (the so-called Honolulu method of somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely condense within the enucleated metaphase II-arrested oocytes, which contain high levels of M-phase-promoting factor (MPF). It is believed that the condensation of the donor chromosomes promotes complete reprogramming of the donor genome within the mouse oocytes. Another key to the success of mouse cloning is the use of blunt micropipettes attached to a piezo impact-driving micromanipulation device. This system saves a significant amount of time during the micromanipulation of oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a group of 20 oocytes can be enucleated within 10 min by an experienced operator. This protocol is composed of seven parts: (1) preparing micropipettes, (2) setting up the enucleation and injection micropipettes, (3) collecting and enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor nuclei, (6) activating embryos and culturing, and (7) transferring cloned embryos. © 2017 Cold Spring Harbor Laboratory Press.

  20. 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

  1. Neuroradiological study of transient ischemic attack

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    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.).

  2. 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.)

  3. Robotic exoskeleton assessment of transient ischemic attack.

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    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.

  4. 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.

  5. 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.

  6. Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management

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    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

  7. Pharmaceutical Sponsorship Bias Influences Thrombolytic Literature in Acute Ischemic Stroke

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    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.

  8. 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)

  9. Mortality study for a decade: ischemic stroke in the elderly.

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    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.

  10. 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.

  11. Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

    Science.gov (United States)

    Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2014-09-05

    Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (pcerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. 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.

  13. [Implementation of a regional system for the emergency care of acute ischemic stroke: Initial results].

    Science.gov (United States)

    Soares-Oliveira, Miguel; Araújo, Fernando

    2014-06-01

    Implementing integrated systems for emergency care of patients with acute ischemic stroke helps reduce morbidity and mortality. We describe the process of organizing and implementing a regional system to cover around 3.7 million people and its main initial results. We performed a descriptive analysis of the implementation process and a retrospective analysis of the following parameters: number of patients prenotified by the pre-hospital system; number of times thrombolysis was performed; door-to-needle time; and functional assessment three months after stroke. The implementation process started in November 2005 and ended in December 2009, and included 11 health centers. There were 3574 prenotifications from the prehospital system. Thrombolysis was performed in 1142 patients. The percentage of patients receiving thrombolysis rose during the study period, with a maximum of 16%. Median door-to-needle time was 62 min in 2009. Functional recovery three months after stroke was total or near total in 50% of patients. The regional system implemented for emergency care of patients with acute ischemic stroke has led to health gains, with progressive improvements in patients' access to thrombolysis, and to greater equity in the health care system, thus helping to reduce mortality from cerebrovascular disease in Portugal. Our results, which are comparable with those of international studies, support the strategy adopted for implementation of this system. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Early Recanalization Postintravenous Thrombolysis in Ischemic Stroke with Large Vessel Occlusion: A Digital Subtraction Angiography Study.

    Science.gov (United States)

    Mao, Yi-Ting; Mitchell, Peter; Churilov, Leonid; Dowling, Richard; Dong, Qiang; Yan, Bernard

    2016-08-01

    We aimed to evaluate early recanalization postintravenous (i.v.) tissue plasminogen activator (t-PA) by digital subtraction angiography (DSA) in acute ischemic stroke (AIS) with large vessel occlusion (LVO). We performed baseline CT angiography to identify LVO in AIS. Recanalization pre- and post-intra-arterial therapy (IAT) was categorized to none, partial, and global recanalization (GR). Modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Among 1610 patients with AIS, 286 received IV t-PA. Of these, 55 patients with LVO were included. The median time from IV t-PA to DSA was 120 min (interquartile range, 79-152). Recanalization post-IV t-PA was observed in seven patients (12.7%). By occlusion sites, the recanalization rates were as follows: extracranial internal carotid artery 2 of 14 (14.3%); intracranial internal carotid artery 3 of 24 (12.5%); M1 of middle cerebral artery 3 of 39 (7.7%); M2 of middle cerebral artery 1 of 40 (2.5%); vertebral artery 0 of 4; and basilar artery 0 of 7. GR post-IAT was associated with favorable outcomes (odds ratio: 8.6; 95% confidence interval, 1.5-48.0; P = 0.014). Early recanalization assessed by DSA post-IV t-PA is rarely observed in acute ischemic stroke patients with LVO. © 2016 John Wiley & Sons Ltd.

  15. [Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

    Science.gov (United States)

    Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

    2017-10-01

    To explore the application value and forensic significance of ischemia modified albumin (IMA) in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group ( n =36), acute myocardial infarction group ( n =6), cardiomyopathy group ( n =4) and control group ( n =15) by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics (ROC) curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group ( P 0.05). The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

  16. Four evolving strategies in the emergent treatment of acute ischemic stroke.

    Science.gov (United States)

    Thurman, R Jason; Jauch, Edward C; Panagos, Peter D; Reynolds, Matthew R; Mocco, J

    2012-07-01

    Stroke is the leading cause of long-term disability in the United States and is the fourth leading cause of death, affecting nearly 800,000 patients each year. The physical, emotional, and financial toll stroke inflicts on patients and their families cannot be overstated. At the forefront of acute stroke care, emergency clinicians are positioned to have a major impact on the quality of care that stroke patients receive. This issue outlines and reviews the literature on 4 evolving strategies reflecting developing advancements in the care of acute ischemic stroke and their potential to impact patients in the emergency department setting: (1) the expanding window for intravenous rt-PA, (2) the use of multimodal computed tomographic scanning in emergent diagnostic imaging, (3) endovascular therapies for stroke, and (4) stroke systems of care. Whether practicing in a tertiary care environment or in a remote emergency department, emergency clinicians will benefit from familiarizing themselves with these advancements and should consider how these new approaches might influence their management of patients with acute ischemic stroke.

  17. Acupuncture for ischemic stroke: cerebellar activation may be a central mechanism following Deqi

    Directory of Open Access Journals (Sweden)

    Miao-keng Li

    2015-01-01

    Full Text Available The needling sensation of Deqi during acupuncture is a key factor of influencing acupuncture outcome. Recent studies have mainly focused on the brain function effects of Deqi in a physiological state. Functional magnetic resonance imaging (fMRI on the effects of acupuncture at Waiguan (SJ5 in pathological and physiological states is controversial. In this study, 12 patients with ischemic stroke received acupuncture at Waiguan (SJ5 and simultaneously underwent fMRI scanning of the brain, with imaging data of the activated areas obtained. Based on the patient′s sensation, imaging data were allocated to either the Deqi group or non-Deqi group. In the Deqi group, the activated/deactivated areas were the left superior temporal gyrus (BA39/right anterior lobe of the cerebellum and left thalamus. In the non-Deqi group, the activated areas included the medial frontal gyrus of the right frontal lobe (BA11, right limbic lobe (BA30, 35, and left frontal lobe (BA47, while the only deactivated area was the right parietal lobe (BA40. Compared with the non-Deqi group, the Deqi group exhibited marked activation of the right anterior lobe of the cerebellum and right limbic lobe (BA30. These findings confirm that the clinical effect of Deqi during acupuncture is based on brain functional changes. Cerebellar activation may be one of the central mechanisms of acupuncture in the treatment of ischemic stroke.

  18. 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)

  19. [Risk factors in cerebrovascular disease. Do transient ischemic attacks lead to changes in lifestyle?].

    Science.gov (United States)

    Sánchez, F; Aguilar, M; Porta, R; Urbano, F; Martínez, I; Bonaventura, I; Ribó, J M

    1994-01-01

    A minor stroke does not cause sufficient alarm in patients to change their lifestyles. 46 patients who suffered strokes in the previous 2 years were contacted by telephone, recording rehabilitation programs, medical therapy and modification of dietary habits. It was discovered that only 50% of those requiring motor rehabilitation actually received such treatment; and only one of twenty carried on speech exercises. Subsequent ischemic events were reported by 22 patients: 12 of whom had strokes, 8 ischemic myocardial attacks and two patients suffered both conditions. The majority of patients followed the prescribed medical treatment and advice badly. Of the 46 patients reviewed, 31 were hypertensive and only 16 follow recommended diets. Out of 15 smokers only, 6 gave up, and from 21 with dislypemia only 10 modified their diets. Of all patients only the most severely affected complied satisfactorily to medical treatments; a possible explanation for this would be that the contact between patients and physician (neurologist and family doctors) was discontinued immediately after the patients discharge from hospital. It is recommended therefore that steps be taken to insure better communication between neurologist, general practitioner and patient; thereby improving prognosis.

  20. 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.

  1. Efficacy and Safety of Platelet Glycoprotein Receptor Blockade in Aged and Comorbid Mice With Acute Experimental Stroke.

    Science.gov (United States)

    Kraft, Peter; Schuhmann, Michael K; Fluri, Felix; Lorenz, Kristina; Zernecke, Alma; Stoll, Guido; Nieswandt, Bernhard; Kleinschnitz, Christoph

    2015-12-01

    Despite the medical and socioeconomic effect of ischemic stroke and extensive preclinical research, treatment options for ischemic stroke are limited. We recently identified and characterized essential steps of thrombus formation in stroke and demonstrated that inhibition of the platelet glycoprotein (GP) receptors Ib and VI, but not IIb/IIIa, protects young and healthy mice from ischemic neurodegeneration. Whether these findings translate to the clinic remains unclear. Considering that the typical stroke patient is elderly with comorbidity, we aimed to analyze the efficacy and safety of novel preclinical antithrombotics in adult and comorbid mice with acute experimental stroke. We subjected adult, healthy, atherosclerotic (Ldlr(-/-)), diabetic (streptozotocin treated), and hypertensive (RenTgMK) mice to a 60-minute transient middle cerebral artery occlusion. Animals were pretreated with anti-GPVI antibodies or treated 1 hour after stroke induction with anti-GPIb or anti-GPIIb/IIIa antigen-binding fragments, respectively. Isotype treatment served as control. Twenty-four hours after transient middle cerebral artery occlusion, we visually assessed the intracerebral hemorrhage rate and measured infarct volumes (using 2,3,5-triphenyltetrazolium chloride-stained brain slices) and functional outcome (using Bederson and grip-test scores). GPIb and GPVI inhibition protected the mice from ischemic stroke without increasing bleeding complications. In contrast, GPIIb/IIIa inhibition was not protective but increased the intracerebral hemorrhage rate. Inhibition of early steps of thrombus formation protects adult and comorbid mice from ischemic stroke. The use of clinically meaningful mouse strains might improve the translation of preclinical stroke research to the clinic. © 2015 American Heart Association, Inc.

  2. Combination of five clinical data as prognostic factors of mortality after ischemic stroke

    Directory of Open Access Journals (Sweden)

    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.

  3. 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...

  4. 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.)

  5. 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.)

  6. 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...

  7. A Case Of Transient Ischemic Attack Presenting As Hemichroea

    Directory of Open Access Journals (Sweden)

    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.

  8. A rare cause of ischemic stroke: Intravasculer B cell lymphoma

    Directory of Open Access Journals (Sweden)

    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.

  9. Ischemic colitis or melanosis coli: a case report

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. 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.

  12. 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...

  13. 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...

  14. Association of the matrix metalloproteinase-3 polymorphisms rs679620 and rs3025058 with ischemic stroke risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhang Q

    2018-01-01

    Full Text Available Qi-Wei Zhang Department of Neurosurgery, The Affiliated Hospital of Jilin Medical University, Jilin, People’s Republic of China Purpose: The relationship of the matrix metalloproteinase-3 (MMP-3 polymorphisms rs679620 and rs3025058 with ischemic stroke has received much attention. The aim of the present study was to perform a meta-analysis of published case–control studies to evaluate the cumulative evidence.Methods: We performed a search of ISI Web of Science, Embase, PubMed, and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs were appropriately derived from fixed-effects or random-effects models.Results: We identified seven eligible studies including 5,204 subjects. The pooled analysis showed that the MMP-3 rs679620 A allele carriers had increased risk of ischemic stroke compared with homozygotes for the G allele in Asians (AA + GA vs GG: OR =1.42, 95% CI: 1.05–1.91, P=0.022. Concerning the rs3025058 polymorphism, the results did not suggest an association between rs3025058 genotypes and ischemic stroke risk (5A5A + 6A5A vs 6A6A: OR =1.04, 95% CI: 0.73–1.47, P=0.844; 5A5A vs 6A5A + 6A6A: OR =1.14, 95% CI: 0.74–1.77, P=0.556; and 5A5A vs 6A6A: OR =1.11, 95% CI: 0.68–1.80, P=0.677. In subgroup analysis by ethnicity, no statistically significant associations were demonstrated for rs3025058 in Asians and Caucasians, respectively. There was no evidence for publication bias.Conclusion: Our findings indicate that the rs679620 A allele carriers have increased risk of ischemic stroke in Asians, but there is no association between rs3025058 and ischemic stroke risk. Keywords: ischemic stroke, meta-analysis, MMP-3, polymorphism

  15. Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice.

    Directory of Open Access Journals (Sweden)

    Nicolas Bréchot

    Full Text Available BACKGROUND: Macrophages, key regulators of healing/regeneration processes, strongly infiltrate ischemic tissues from patients suffering from critical limb ischemia (CLI. However pro-inflammatory markers correlate with disease progression and risk of amputation, suggesting that modulating macrophage activation state might be beneficial. We previously reported that thrombospondin-1 (TSP-1 is highly expressed in ischemic tissues during CLI in humans. TSP-1 is a matricellular protein that displays well-known angiostatic properties in cancer, and regulates inflammation in vivo and macrophages properties in vitro. We therefore sought to investigate its function in a mouse model of CLI. METHODS AND FINDINGS: Using a genetic model of tsp-1(-/- mice subjected to femoral artery excision, we report that tsp-1(-/- mice were clinically and histologically protected from necrosis compared to controls. Tissue protection was associated with increased postischemic angiogenesis and muscle regeneration. We next showed that macrophages present in ischemic tissues exhibited distinct phenotypes in tsp-1(-/- and wt mice. A strong reduction of necrotic myofibers phagocytosis was observed in tsp-1(-/- mice. We next demonstrated that phagocytosis of muscle cell debris is a potent pro-inflammatory signal for macrophages in vitro. Consistently with these findings, macrophages that infiltrated ischemic tissues exhibited a reduced postischemic pro-inflammatory activation state in tsp-1(-/- mice, characterized by a reduced Ly-6C expression and a less pro-inflammatory cytokine expression profile. Finally, we showed that monocyte depletion reversed clinical and histological protection from necrosis observed in tsp-1(-/- mice, thereby demonstrating that macrophages mediated tissue protection in these mice. CONCLUSION: This study defines targeting postischemic macrophage activation state as a new potential therapeutic approach to protect tissues from necrosis and promote tissue

  16. Effect of helicopter transport on neurological outcomes in a mouse model of embolic stroke with reperfusion: AIR-MICE pilot study.

    Science.gov (United States)

    Leira, Enrique C; Zaheer, Asgar; Schnell, Thomas; Torner, James C; Olalde, Heena M; Pieper, Andrew A; Ortega-Gutierrez, Santiago; Nagaraja, Nandakumar; Marks, Nancy L; Adams, Harold P

    2015-10-01

    Patients often suffer a stroke at a significant distance from a center capable of delivering endovascular therapy, thus requiring rapid transport by helicopter emergency medical services while receiving a recombinant tissue plasminogen activator infusion that was initiated locally. But little is known about how a helicopter flight may impact the safety and efficacy of recombinant tissue plasminogen activator-induced reperfusion and patient outcomes. To establish a new animal method to address with fidelity the safety and overall effect of helicopter emergency medical services during thrombolysis. Prospective randomized open blinded end-point study of an actual helicopter flight exposure. Adult C57BL/6 male mice were treated with a 10 mg/kg recombinant tissue plasminogen activator infusion two-hours after an embolic middle cerebral artery occlusion. Mice were randomized in pairs to simultaneously receive the infusion during a local helicopter flight or in a ground hangar. Eighteen mice (nine pairs) were analyzed. The paired t-test analysis showed nonsignificant smaller infarction volumes in the helicopter-assigned animals (mean pair difference 33 mm(3) , P = 0·33). The amount of hemorrhagic transformation between the helicopter and ground groups was 4·08 vs. 4·56 μl, respectively (paired t-test, P = 0·45). This study shows that helicopter emergency medical services do not have an inherent adverse effect on outcome in a mouse model of ischemic stroke with reperfusion. These results endorse the safety of the practice of using helicopter emergency medical services in stroke patients. The observed potential synergistic effect of helicopter-induced factors, such as vibration and changes in altitude, with reperfusion merits further exploration in animal experimental models and in stroke patients. © 2015 World Stroke Organization.

  17. The Siblings With Ischemic Stroke Study (SWISS Protocol

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. Automatic classification of cardioembolic and arteriosclerotic ischemic strokes from apparent diffusion coefficient datasets using texture analysis and deep learning

    Science.gov (United States)

    Villafruela, Javier; Crites, Sebastian; Cheng, Bastian; Knaack, Christian; Thomalla, Götz; Menon, Bijoy K.; Forkert, Nils D.

    2017-03-01

    Stroke is a leading cause of death and disability in the western hemisphere. Acute ischemic strokes can be broadly classified based on the underlying cause into atherosclerotic strokes, cardioembolic strokes, small vessels disease, and stroke with other causes. The ability to determine the exact origin of an acute ischemic stroke is highly relevant for optimal treatment decision and preventing recurrent events. However, the differentiation of atherosclerotic and cardioembolic phenotypes can be especially challenging due to similar appearance and symptoms. The aim of this study was to develop and evaluate the feasibility of an image-based machine learning approach for discriminating between arteriosclerotic and cardioembolic acute ischemic strokes using 56 apparent diffusion coefficient (ADC) datasets from acute stroke patients. For this purpose, acute infarct lesions were semi-atomically segmented and 30,981 geometric and texture image features were extracted for each stroke volume. To improve the performance and accuracy, categorical Pearson's χ2 test was used to select the most informative features while removing redundant attributes. As a result, only 289 features were finally included for training of a deep multilayer feed-forward neural network without bootstrapping. The proposed method was evaluated using a leave-one-out cross validation scheme. The proposed classification method achieved an average area under receiver operator characteristic curve value of 0.93 and a classification accuracy of 94.64%. These first results suggest that the proposed image-based classification framework can support neurologists in clinical routine differentiating between atherosclerotic and cardioembolic phenotypes.

  1. Change apparent diffusion coefficient immediately after recanalization through intra-arterial revascularization therapy in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Ji Eun; Yeom, Joeng A; Kim, Young Soo; Yoon, Chang Hyo; Park, Min Gyu; Park, Kyung Pil; Baik, Seung Kug [Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2016-04-15

    Intra-arterial revascularization therapy (IART) for acute ischemic stroke has become increasingly popular recently. However, early change in apparent diffusion coefficient (ADC) values after full recanalization in human stroke has not received much attention. The aim of this study was to evaluate ADC changes immediately after interventional full-recanalization in patients with acute ischemic stroke. ADC values of 25 lesions from 18 acute ischemic stroke patients were recorded with both pre- and post-recanalization ADC maps. Measurement was done by placing region of interests over the representative images of the lesion. For analysis, lesions were divided into territorial infarction (TI) and watershed infarction (WI). Mean ADC values of the overall 25 lesions before IART were 415.12 × 10-6 mm{sup 2}/sec, and increased to 619.08 × 10-6 mm{sup 2}/sec after the IART. Average relative ADC (rADC) value for 22 TI increased from 0.59 to 0.92 (p < 0.000), whereas, average rADC value for 3 WI did not change significantly. There was a conspicuous increase of ADC values immediately after full-recanalization in TI lesions. On the other hand, WI lesions did not show significant change in ADC values after recanalization.

  2. Predicting final extent of ischemic infarction using artificial neural network analysis of multi-parametric MRI in patients with stroke.

    Directory of Open Access Journals (Sweden)

    Hassan Bagher-Ebadian

    Full Text Available In hemispheric ischemic stroke, the final size of the ischemic lesion is the most important correlate of clinical functional outcome. Using a set of acute-phase MR images (Diffusion-weighted--DWI, T(1-weighted--T1WI, T(2-weighted--T2WI, and proton density weighted--PDWI for inputs, and the chronic T2WI at 3 months as an outcome measure, an Artificial Neural Network (ANN was trained to predict the 3-month outcome in the form of a voxel-by-voxel forecast of the chronic T2WI. The ANN was trained and tested using 12 subjects (with 83 slices and 140218 voxels using a leave-one-out cross-validation method with calculation of the Area Under the Receiver Operator Characteristic Curve (AUROC for training, testing and optimization of the ANN. After training and optimization, the ANN produced maps of predicted outcome that were well correlated (r = 0.80, p<0.0001 with the T2WI at 3 months for all 12 patients. This result implies that the trained ANN can provide an estimate of 3-month ischemic lesion on T2WI in a stable and accurate manner (AUROC = 0.89.

  3. Improvement of Detection of Hypoattenuation in Acute Ischemic Stroke in Unenhanced Computed Tomography Using an Adaptive Smoothing Filter

    International Nuclear Information System (INIS)

    Takahashi, N.; Lee, Y.; Tsai, D. Y.; Ishii, K.; Kinoshita, T.; Tamura, H.; K imura, M.

    2008-01-01

    Background: Much attention has been directed toward identifying early signs of cerebral ischemia on computed tomography (CT) images. Hypoattenuation of ischemic brain parenchyma has been found to be the most frequent early sign. Purpose: To evaluate the effect of a previously proposed adaptive smoothing filter for improving detection of parenchymal hypoattenuation of acute ischemic stroke on unenhanced CT images. Material and Methods: Twenty-six patients with parenchymal hypoattenuation and 49 control subjects without hypoattenuation were retrospectively selected in this study. The adaptive partial median filter (APMF) designed for improving detectability of hypoattenuation areas on unenhanced CT images was applied. Seven radiologists, including four certified radiologists and three radiology residents, indicated their confidence level regarding the presence (or absence) of hypoattenuation on CT images, first without and then with the APMF processed images. Their performances without and with the APMF processed images were evaluated by receiver operating characteristic (ROC) analysis. Results: The mean areas under the ROC curves (AUC) for all observers increased from 0.875 to 0.929 (P=0.002) when the radiologists observed with the APMF processed images. The mean sensitivity in the detection of hypoattenuation significantly improved, from 69% (126 of 182 observations) to 89% (151 of 182 observations), when employing the APMF (P=0.012). The specificity, however, was unaffected by the APMF (P=0.41). Conclusion: The APMF has the potential to improve the detection of parenchymal hypoattenuation of acute ischemic stroke on unenhanced CT images

  4. Changes in lactate dehydrogenase are associated with central gray matter lesions in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Yum, Sook Kyung; Moon, Cheong-Jun; Youn, Young-Ah; Sung, In Kyung

    2017-05-01

    Biomarkers may predict neurological prognosis in infants with hypoxic-ischemic encephalopathy (HIE). We evaluated the relationship between serum lactate dehydrogenase (LDH) and brain magnetic resonance imaging (MRI), which predicts neurodevelopmental outcomes, in order to assess whether LDH levels are similarly predictive. Medical records were reviewed for infants with HIE and LDH levels were assessed on the first (LDH 1 ) and third (LDH 3 ) days following birth. Receiver operating characteristic curves were obtained in relation to central gray matter hypoxic-ischemic lesions. Of 92 patients, 52 (56.5%) had hypoxic-ischemic lesions on brain MRI, and 21 of these infants (40.4%) had central gray matter lesions. LDH 1 and LDH 3 did not differ; however, the percentage change (ΔLDH%) was significantly higher in infants with central gray matter lesions (36.9% versus 6.6%, p = 0.006). With cutoffs of 187 (IU/L, ΔLDH) and 19.4 (%, ΔLDH%), the sensitivity, specificity, positive predictive value and negative predictive value were 71.4, 69.0, 40.5 and 89.1%, respectively. The relative risk was 5.57 (p = 0.001). Changes in serum LDH may be a useful biomarker for predicting future neurodevelopmental prognosis in infants with HIE.

  5. Change apparent diffusion coefficient immediately after recanalization through intra-arterial revascularization therapy in acute ischemic stroke

    International Nuclear Information System (INIS)

    Roh, Ji Eun; Yeom, Joeng A; Kim, Young Soo; Yoon, Chang Hyo; Park, Min Gyu; Park, Kyung Pil; Baik, Seung Kug

    2016-01-01

    Intra-arterial revascularization therapy (IART) for acute ischemic stroke has become increasingly popular recently. However, early change in apparent diffusion coefficient (ADC) values after full recanalization in human stroke has not received much attention. The aim of this study was to evaluate ADC changes immediately after interventional full-recanalization in patients with acute ischemic stroke. ADC values of 25 lesions from 18 acute ischemic stroke patients were recorded with both pre- and post-recanalization ADC maps. Measurement was done by placing region of interests over the representative images of the lesion. For analysis, lesions were divided into territorial infarction (TI) and watershed infarction (WI). Mean ADC values of the overall 25 lesions before IART were 415.12 × 10-6 mm 2 /sec, and increased to 619.08 × 10-6 mm 2 /sec after the IART. Average relative ADC (rADC) value for 22 TI increased from 0.59 to 0.92 (p < 0.000), whereas, average rADC value for 3 WI did not change significantly. There was a conspicuous increase of ADC values immediately after full-recanalization in TI lesions. On the other hand, WI lesions did not show significant change in ADC values after recanalization

  6. Solar advanced internal film receiver

    International Nuclear Information System (INIS)

    Torre Cabezas, M. de la

    1990-01-01

    In a Solar Central Internal Film Receiver, the heat absorbing fluid (a molten nitrate salt) flows in a thin film down over the non illuminated side of an absorber panel. Since the molten salt working fluid is not contained in complicated tube manifolds, the receiver design is simples than a conventional tube type-receiver resulting in a lower cost and a more reliable receiver. The Internal Film Receiver can be considered as an alternative to the Direct Absorption Receiver, in the event that the current problems of the last one can not be solved. It also describes here the test facility which will be used for its solar test, and the test plans foreseen. (Author) 17 refs

  7. Communications receivers principles and design

    CERN Document Server

    Rohde, Ulrich L; Zahnd, Hans

    2017-01-01

    This thoroughly updated guide offers comprehensive explanations of the science behind today’s radio receivers along with practical guidance on designing, constructing, and maintaining real-world communications systems. You will explore system planning, antennas and antenna coupling, amplifiers and gain control, filters, mixers, demodulation, digital communication, and the latest software defined radio (SDR) technology. Written by a team of telecommunication experts, Communications Receivers: Principles and Design, Fourth Edition, features technical illustrations, schematic diagrams, and detailed examples. Coverage includes: • Basic radio considerations • Radio receiver characteristics • Receiver system planning • Receiver implementation considerations • RF and baseband techniques for Software-Defined Radios • Transceiver SDR considerations • Antennas and antenna coupling • Mixers • Frequency sources and control • Ancillary receiver circuits • Performance measurement

  8. The protective effect of ischemic preconditioning on rat testis

    Directory of Open Access Journals (Sweden)

    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

  9. 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...

  10. 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.

  11. 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...

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

    Science.gov (United States)

    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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

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

    Science.gov (United States)

    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.

  19. 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, 6.0-1