The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Sidney Strickland - One of the best experts on this subject based on the ideXlab platform.
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key role of Tissue Plasminogen Activator in neurovascular coupling
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Laibaik Park, Sidney Strickland, Eduardo F Gallo, Josef Anrather, Gang Wang, Erin H Norris, Justin Paul, Costantino IadecolaAbstract:The increase in blood flow evoked by synaptic activity is essential for normal brain function and underlies functional brain imaging signals. Nitric oxide, a vasodilator released by NMDA receptor activation, is critical for the flow increase, but the factors linking NMDA receptor activity to nitric oxide-dependent hyperemia are poorly understood. Here, we show that Tissue Plasminogen Activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by somatosensory stimulation. tPA acts by facilitating neuronal nitric oxide release, but this effect does not involve enhancement of NMDA currents or the associated intracellular Ca2+ rise. Rather, the evidence suggests that tPA controls NMDA-dependent nitric oxide synthesis by influencing the phosphorylation state of neuronal nitric oxide synthase. These findings unveil a previously unrecognized role of tPA in vital homeostatic mechanisms coupling NMDA receptor signaling with nitric oxide synthesis and local cerebral perfusion.
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Tissue Plasminogen Activator in central nervous system physiology and pathology
Thrombosis and Haemostasis, 2005Co-Authors: Jerry P Melchor, Sidney StricklandAbstract:Although conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the Tissue Plasminogen Activator (tPA)/Plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain.
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Tissue Plasminogen Activator in the amygdala is critical for stress induced anxiety like behavior
Nature Neuroscience, 2003Co-Authors: Robert Pawlak, Jerry P Melchor, Ana Maria Magarinos, Bruce S Mcewen, Sidney StricklandAbstract:Although neuronal stress circuits have been identified, little is known about the mechanisms that underlie the stress-induced neuronal plasticity leading to fear and anxiety. Here we found that the serine protease Tissue-Plasminogen Activator (tPA) was upregulated in the central and medial amygdala by acute restraint stress, where it promoted stress-related neuronal remodeling and was subsequently inhibited by Plasminogen Activator inhibitor-1 (PAI-1). These events preceded stress-induced increases in anxiety-like behavior of mice. Mice in which the tPA gene has been disrupted did not show anxiety after up to three weeks of daily restraint and showed attenuated neuronal remodeling as well as a maladaptive hormonal response. These studies support the idea that tPA is critical for the development of anxiety-like behavior after stress.
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Tissue Plasminogen Activator in nervous system function and dysfunction
Thrombosis and Haemostasis, 2001Co-Authors: Sidney StricklandAbstract:The extracellular protease Tissue Plasminogen Activator (tPA) has been implicated in various normal and pathological situations in the mammalian nervous system. The availability of (i) transgenic and knock-out mice in which the expression level of tPA can be widely varied, (ii) in vivo models for studying function and disease, and (iii) culture models for examining cell behavior, has allowed a detailed evaluation of many of these proposed functions. This chapter summarizes the current state of knowledge of possible roles for the tPA/Plasminogen system in neuronal function and dysfunction.
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activation of microglia reveals a non proteolytic cytokine function for Tissue Plasminogen Activator in the central nervous system
Journal of Cell Science, 1999Co-Authors: Andrew D Rogove, Chiajen Siao, Bruce Keyt, Sidney Strickland, Stella E TsirkaAbstract:Tissue Plasminogen Activator mediates excitotoxin-induced neurodegeneration and microglial activation in the mouse hippocampus. Here we show that Tissue Plasminogen Activator (tPA) acts in a protease-independent manner to modulate the activation of microglia, the cells of the central nervous system with macrophage properties. Cultured microglia from tPA-deficient mice can phagocytose as efficiently as wild-type microglia. However, tPA-deficient microglia in mixed cortical cultures exhibit attenuated activation in response to lipopolysaccharide, as judged by morphological changes, increased expression of the activation marker F4/80 and the release of the pro-inflammatory cytokine tumor necrosis factor-(α). When tPA is added to tPA deficient cortical cultures prior to endotoxin stimulation, microglial activation is restored to levels comparable to that observed in wild-type cells. Proteolytically-inactive tPA can also restore activation of tPA-deficient microglia in culture and in vivo. However, this inactive enzyme does not restore susceptibility of tPA-deficient hippocampal neurons to excitotoxin-mediated cell death. These results dissociate two different functions of tPA: inactive enzyme can mediate microglial activation, whereas proteolytically-competent protein also promotes neuronal degeneration. Thus tPA is identified as a new cytokine in the central nervous system.
David Tanne - One of the best experts on this subject based on the ideXlab platform.
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hemostatic activation and outcome after recombinant Tissue Plasminogen Activator therapy for acute ischemic stroke
Stroke, 2006Co-Authors: Barbara C Tilley, David Tanne, Richard F Macko, Yan Lin, Steven R LevineAbstract:Background and Purpose— Early thrombolytic therapy with intravenous recombinant Tissue Plasminogen Activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. Methods— Tissue Plasminogen Activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. Results— TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for inter...
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initial clinical experience with iv Tissue Plasminogen Activator for acute ischemic stroke a multicenter survey
Neurology, 1999Co-Authors: David Tanne, Vernice E Bates, Piero Verro, Scott E Kasner, Jeffrey R Binder, Suresh C Patel, H H Mansbach, S Daley, Lonni SchultzAbstract:Article abstract We assessed initial clinical experience with IV Tissue Plasminogen Activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.
Steven R Levine - One of the best experts on this subject based on the ideXlab platform.
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strokes with minor symptoms an exploratory analysis of the national institute of neurological disorders and stroke recombinant Tissue Plasminogen Activator trials
Stroke, 2010Co-Authors: Pooja Khatri, Steven R Levine, Dawn Kleindorfer, Sharon D Yeatts, Jeffrey L Saver, Patrick D Lyden, Charles J Moomaw, Yuko Y Palesch, Edward C Jauch, Joseph P BroderickAbstract:Background and Purpose—The pivotal National Institute of Neurological Disorders and Stroke recombinant Tissue Plasminogen Activator trials excluded patients with ischemic stroke with specific minor presentations or rapidly improving symptoms. The recombinant Tissue Plasminogen Activator product label notes that its use for minor neurological deficit or rapidly improving stroke symptoms has not been evaluated. As a result, patients with low National Institutes of Health Stroke Scale scores are not commonly treated in clinical practice. We sought to further characterize the patients with minor stroke who were included in the National Institute of Neurological Disorders and Stroke trials. Methods—Minor strokes were defined as National Institutes of Health Stroke Scale score ≤5 at baseline for this retrospective analysis, because this subgroup is most commonly excluded from treatment in clinical practice and trials. Clinical stroke syndromes were defined based on prespecified National Institutes of Health Str...
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hemostatic activation and outcome after recombinant Tissue Plasminogen Activator therapy for acute ischemic stroke
Stroke, 2006Co-Authors: Barbara C Tilley, David Tanne, Richard F Macko, Yan Lin, Steven R LevineAbstract:Background and Purpose— Early thrombolytic therapy with intravenous recombinant Tissue Plasminogen Activator (rtPA) improves clinical outcome in acute ischemic stroke (AIS), but impaired endogenous fibrinolysis, thrombin generation, and vascular injury may hamper the efficacy of thrombolysis. We investigated in an exploratory, post hoc analysis the relationship between hemostatic markers and clinical outcomes among patients included in the National Institute of Neurological Disorders and Stroke (NINDS) rtPA Stroke Study. Methods— Tissue Plasminogen Activator (tPA) antigen, thrombin-antithrombin complex (TAT), soluble thrombomodulin, and fibrinogen levels were measured in patients with AIS included in the NINDS rtPA Stroke Study from plasma samples collected at baseline, at 2 hours after treatment, and after 24 hours. Results— TAT and tPA antigen levels peaked at 2 hours selectively in the rtPA treatment group, whereas fibrinogen levels dropped at 2 hours and remained low after 24 hours (P<0.0001 for inter...
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effects of Tissue Plasminogen Activator for acute ischemic stroke at one year
The New England Journal of Medicine, 1999Co-Authors: Thomas Kwiatkowski, Joseph P Broderick, Richard B Libman, Michael Frankel, Barbara C Tilley, Lewis B Morgenstern, Mei Lu, Christopher Lewandowski, John R Marler, Steven R LevineAbstract:Background In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study found that patients who were treated with Tissue Plasminogen Activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. Methods In the NINDS trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a “favorable outcome,” defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Results Using an intention-to-treat analysis for the comb...
Ying Xian - One of the best experts on this subject based on the ideXlab platform.
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abstract 12291 intravenous recombinant Tissue Plasminogen Activator in acute ischemic stroke patients with gastrointestinal malignancy or recent bleeding
Circulation, 2018Co-Authors: Taku Inohara, Li Liang, Andrzej S Kosinski, Eric E Smith, Lee H Schwamm, Adrian F Hernandez, Deepak L Bhatt, Gregg C Fonarow, Eric D Peterson, Ying XianAbstract:Introduction: Based on expert consensus, the use of intravenous recombinant Tissue Plasminogen Activator (rtPA) for treating acute ischemic stroke (AIS) is contraindicated in patients with a gastro...
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abstract tp314 current use of strategies to improve door to needle times with Tissue Plasminogen Activator in acute ischemic stroke findings from the target stroke phase ii survey
Stroke, 2016Co-Authors: Ying Xian, Eric E Smith, Adrian F Hernandez, Eric D Peterson, Jeffrey L Saver, Barbara L Lytle, Jason R Blevins, Steven R Messe, Mary Paulsen, Robert E SuterAbstract:Background: The benefits of intravenous Tissue Plasminogen Activator (IV tPA) in acute ischemic stroke are time-dependent. The implementation of Target: Stroke Phase I, the first stage of the Ameri...
Michael B Silva - One of the best experts on this subject based on the ideXlab platform.
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treatment of portal venous thrombosis with selective superior mesenteric artery infusion of recombinant Tissue Plasminogen Activator
Journal of Vascular Surgery, 2003Co-Authors: E A Henao, Todd W Bohannon, Michael B SilvaAbstract:Portal and mesenteric venous thrombosis is an uncommon condition that is usually treated with systemic anticoagulation. Catheter-directed thrombolysis via the superior mesenteric artery may be a viable adjunct to treatment of this potentially morbid condition. We present a case of portal and mesenteric venous thrombosis treated with systemic anticoagulation and catheter-directed infusion of Tissue Plasminogen Activator via the superior mesenteric artery.
