tissue plasminogen activator

Summary

Summary: A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to PLASMIN. It has fibrin-binding activity and is immunologically different from URINARY PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68.

Top Publications

  1. ncbi Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
    Werner Hacke
    Department of Neurology, Universitat Heidelberg, Heidelberg, Germany
    N Engl J Med 359:1317-29. 2008
  2. pmc Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis
    Joanna M Wardlaw
    Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Lancet 379:2364-72. 2012
  3. ncbi Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atheros
    Harold P Adams
    Stroke 38:1655-711. 2007
  4. pmc Factors affecting the apparent efficacy and safety of tissue plasminogen activator in thrombotic occlusion models of stroke: systematic review and meta-analysis
    Emily S Sena
    Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    J Cereb Blood Flow Metab 30:1905-13. 2010
  5. ncbi Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials
    Kennedy R Lees
    Department of Medicine and Therapeutics, Faculty of Medicine, University of Glasgow, Western Infirmary, Glasgow, UK
    Lancet 375:1695-703. 2010
  6. ncbi Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study
    Nils Wahlgren
    Department of Neurology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Lancet 369:275-82. 2007
  7. ncbi Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atheros
    Harold P Adams
    University of Iowa Carver College of Medicine, USA
    Circulation 115:e478-534. 2007
  8. ncbi Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators
    W Hacke
    Department of Neurology, University of Heidelberg, Germany
    Lancet 352:1245-51. 1998
  9. ncbi Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke
    Jeffrey L Saver
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    JAMA 309:2480-8. 2013
  10. ncbi Physiological consequences of loss of plasminogen activator gene function in mice
    P Carmeliet
    Whitehead Institute of Biomedical Research, Cambridge, Massachusetts 02142
    Nature 368:419-24. 1994

Detail Information

Publications392 found, 100 shown here

  1. ncbi Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
    Werner Hacke
    Department of Neurology, Universitat Heidelberg, Heidelberg, Germany
    N Engl J Med 359:1317-29. 2008
    ..We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke...
  2. pmc Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis
    Joanna M Wardlaw
    Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Lancet 379:2364-72. 2012
    Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely...
  3. ncbi Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atheros
    Harold P Adams
    Stroke 38:1655-711. 2007
    ..The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included...
  4. pmc Factors affecting the apparent efficacy and safety of tissue plasminogen activator in thrombotic occlusion models of stroke: systematic review and meta-analysis
    Emily S Sena
    Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
    J Cereb Blood Flow Metab 30:1905-13. 2010
    Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome in animal models of stroke and in clinical trial, but is associated with increased intracranial hemorrhage...
  5. ncbi Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials
    Kennedy R Lees
    Department of Medicine and Therapeutics, Faculty of Medicine, University of Glasgow, Western Infirmary, Glasgow, UK
    Lancet 375:1695-703. 2010
    Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome...
  6. ncbi Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study
    Nils Wahlgren
    Department of Neurology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Lancet 369:275-82. 2007
    ..Under European Union regulations, SITS-MOST was required to assess the safety profile of alteplase in clinical practice by comparison with results in randomised controlled trials...
  7. ncbi Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atheros
    Harold P Adams
    University of Iowa Carver College of Medicine, USA
    Circulation 115:e478-534. 2007
    ..The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included...
  8. ncbi Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators
    W Hacke
    Department of Neurology, University of Heidelberg, Germany
    Lancet 352:1245-51. 1998
    ..We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0.9 mg/kg bodyweight) within 6 h of stroke onset...
  9. ncbi Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke
    Jeffrey L Saver
    Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    JAMA 309:2480-8. 2013
    ..However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain...
  10. ncbi Physiological consequences of loss of plasminogen activator gene function in mice
    P Carmeliet
    Whitehead Institute of Biomedical Research, Cambridge, Massachusetts 02142
    Nature 368:419-24. 1994
    ..Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival...
  11. ncbi National US estimates of recombinant tissue plasminogen activator use: ICD-9 codes substantially underestimate
    Dawn Kleindorfer
    University of Cincinnati College of Medicine, Department of Neurology, 231 Albert Sabin Way ML 0525, Cincinnati, Ohio 45267 0525, USA
    Stroke 39:924-8. 2008
    Current US estimates of recombinant tissue plasminogen activator (rt-PA) use have been based either on extrapolation of regional studies or on administrative database estimates, both of which may have inherent biases...
  12. ncbi Using recombinant tissue plasminogen activator to treat acute ischemic stroke in China: analysis of the results from the Chinese National Stroke Registry (CNSR)
    Yilong Wang
    Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 6 Tiantanxili, Chongwen District, Beijing, China
    Stroke 42:1658-64. 2011
    Little is known about intravenous recombinant tissue plasminogen activator (rtPA) use in China. By accessing the Chinese National Stroke Registry (CNSR), the rate of intravenous rtPA use was reviewed...
  13. ncbi Plasmin cleavage of the amyloid beta-protein: alteration of secondary structure and stimulation of tissue plasminogen activator activity
    W E Van Nostrand
    Department of Medicine, Health Sciences Center, State University of New York, Stony Brook 11794 8153, USA
    Biochemistry 38:11570-6. 1999
    ..These findings suggest that pathologic interactions between A beta, tPA, and plasmin in the cerebral vessel wall could result in excessive proteolysis contributing to intracerebral hemorrhages...
  14. ncbi Survey of emergency physicians about recombinant tissue plasminogen activator for acute ischemic stroke
    Devin L Brown
    University of Michigan Health System, Ann Arbor, MI, USA
    Ann Emerg Med 46:56-60. 2005
    The use of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke is controversial among emergency physicians...
  15. ncbi Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke
    Joan Montaner
    Cerebrovascular Unit, Vall d Hebron Hospital, Barcelona, Spain
    Circulation 107:598-603. 2003
    ..Moreover, MMP inhibitors reduce hemorrhagic transformation (HT) after embolic ischemia in tissue plasminogen activator (t-PA)-treated animals...
  16. ncbi High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor
    A M Thögersen
    Department of Medicine, Clinical Chemistry, and Nutritional Research and Pathology Umeå University Hospital, University of Umea, Sweden
    Circulation 98:2241-7. 1998
    ..So far, there have been no primary prospective studies of PAI-1...
  17. ncbi Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory
    P Calabresi
    Clinica Neurologica, Dip Neuroscienze, Universita di Tor Vergata, Via di Tor Vergata 135, Rome 00133, Italy
    Eur J Neurosci 12:1002-12. 2000
    ..These data indicate that t-PA plays a critical role in the formation of various forms of synaptic plasticity and memory...
  18. ncbi Intrapleural use of tissue plasminogen activator and DNase in pleural infection
    Najib M Rahman
    UKCRC Oxford Respiratory Trials Unit, Oxford Centre for Respiratory Medicine, Nuffield Department of Medicine, University of Oxford, Churchill Hospital Site, Headington, Oxford OX3 7LJ, United Kingdom
    N Engl J Med 365:518-26. 2011
    ..Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial...
  19. pmc Endogenous tissue plasminogen activator mediates bone marrow stromal cell-induced neurite remodeling after stroke in mice
    Li Hong Shen
    Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA
    Stroke 42:459-64. 2011
    ..We investigated the effects of endogenous tissue plasminogen activator (tPA) on neurite remodeling after BMSC treatment.
  20. ncbi Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage
    Violeta Lukic-Panin
    Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
    Curr Neurovasc Res 7:319-29. 2010
    One of the therapeutics for acute cerebral ischemia is tissue plasminogen activator (t-PA). Using t-PA after 3 hour time window increases the chances of hemorrhage, involving multiple mechanisms...
  21. ncbi Optimizing the management of acute ischaemic stroke: a review of the utilization of intravenous recombinant tissue plasminogen activator (tPA)
    A Eissa
    Faculty of Pharmacy, University of Sydney, NSW, Australia
    J Clin Pharm Ther 37:620-9. 2012
    Thrombolysis using intravenous tissue plasminogen activator (tPA) is the only available evidence-based treatment for acute ischaemic stroke; however, its current utilization is very low...
  22. ncbi Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system
    Tambet Teesalu
    Haartman Institute, University of Helsinki and HUCH Laboratory Diagnostics, Finland
    Thromb Haemost 92:358-68. 2004
    b>Tissue plasminogen activator (tPA) is increasingly recognized to play important roles in various physiological and pathological processes in the central nervous system (CNS)...
  23. ncbi Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats
    Jie Jen Lee
    Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan
    J Ethnopharmacol 134:824-30. 2011
    ..to the hospital with acute ischemic stroke are initially considered candidates for the recombinant tissue plasminogen activator (rt-PA). However, rt-PA therapy is still lesser than ideal due to its major side effect of hemorrhaging...
  24. ncbi A proposed reference method for plasminogen activators that enables calculation of enzyme activities in SI units
    C Longstaff
    Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK
    J Thromb Haemost 2:1416-21. 2004
    ..of a range of plasminogen activators (PAs) used as thrombolytic agents, including streptokinase, tissue plasminogen activator (tPA) and variants, and urokinase (uPA), both single and two chain forms...
  25. ncbi Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study
    Dawn Kleindorfer
    Department of Neurology, University of Cincinnati College of Medicine, The Neuroscience Institute, OH 45267, USA
    Stroke 35:e27-9. 2004
    Acute ischemic stroke patients are infrequently treated with recombinant tissue plasminogen activator (rtPA). We present unique population-based data regarding the eligibility of ischemic stroke patients for rtPA treatment.
  26. pmc Tissue plasminogen activator is a potent activator of PDGF-CC
    Linda Fredriksson
    Ludwig Institute for Cancer Research, Stockholm Branch, Stockholm, Sweden
    EMBO J 23:3793-802. 2004
    b>Tissue plasminogen activator (tPA) is a serine protease involved in the degradation of blood clots through the activation of plasminogen to plasmin...
  27. ncbi Intra-arterial tumor necrosis factor-alpha impairs endothelium-dependent vasodilatation and stimulates local tissue plasminogen activator release in humans
    Stanley Chia
    Department of Cardiology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK
    Arterioscler Thromb Vasc Biol 23:695-701. 2003
    ..We assessed the direct effects of local intra-arterial tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and endotoxin on blood flow and endogenous tissue plasminogen activator (t-PA) release in vivo in humans.
  28. ncbi Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival
    G A Hastings
    Department of Protein Therapeutics, Human Genome Sciences Inc, Rockville, Maryland 20850, USA
    J Biol Chem 272:33062-7. 1997
    ..Taken together, these data suggest that neuroserpin is likely to be a critical regulator of tPA activity in the central nervous system, and as such may play an important role in neuronal plasticity and/or maintenance...
  29. ncbi Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic
    Manuel Yepes
    Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
    Trends Neurosci 32:48-55. 2009
    ..Here, the best studied pathways of tPA neurotoxicity are discussed along with future directions for a safer use of tPA as a thrombolytic agent in the setting of acute ischemic stroke...
  30. ncbi Differences in clot preparation determine outcome of recombinant tissue plasminogen activator treatment in experimental thromboembolic stroke
    Frank Niessen
    Department of Experimental Neurology, Max Planck Institute for Neurological Research, Gleueler Strasse 50, D 50931 Cologne, Germany
    Stroke 34:2019-24. 2003
    ..Thrombin-induced clots used in experimental thromboembolic stroke differ from clots forming spontaneously under clinical conditions. We investigated whether this difference influences the efficacy and outcome of thrombolytic treatment...
  31. pmc Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein
    Manuel Yepes
    Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA
    J Clin Invest 112:1533-40. 2003
    ....
  32. pmc Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus
    Robert Pawlak
    Department of Cell Physiology and Pharmacology, University of Leicester, UK
    Proc Natl Acad Sci U S A 102:18201-6. 2005
    ..NMDA receptors coincides spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity...
  33. ncbi An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus
    S E Tsirka
    Department of Pharmacology, University Medical Center at Stony Brook, New York 11794 8651, USA
    J Neurosci 17:543-52. 1997
    Mice lacking the serine protease tissue plasminogen activator (tPA) are resistant to excitotoxin-mediated hippocampal neuronal degeneration. We have used genetic and cellular analyses to study the role of tPA in neuronal cell death...
  34. ncbi Tissue plasminogen activator binding to the annexin II tail domain. Direct modulation by homocysteine
    K A Hajjar
    Department of Pediatrics, Cornell University Medical College, New York, New York 10021, USA
    J Biol Chem 273:9987-93. 1998
    b>Tissue plasminogen activator binds to endothelial cells via the calcium-regulated phospholipid-binding protein annexin II, an interaction that is inhibited by the prothrombotic amino acid homocysteine...
  35. pmc Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse
    Hongqi Xin
    Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America
    PLoS ONE 5:e9027. 2010
    We demonstrate that tissue plasminogen activator (tPA) and its inhibitors contribute to neurite outgrowth in the central nervous system (CNS) after treatment of stroke with multipotent mesenchymal stromal cells (MSCs)...
  36. ncbi Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior
    Robert Pawlak
    Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Neurosci 6:168-74. 2003
    ..These studies support the idea that tPA is critical for the development of anxiety-like behavior after stress...
  37. pmc Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies
    Rao Muralikrishna Adibhatla
    Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
    CNS Neurol Disord Drug Targets 7:243-53. 2008
    ....
  38. pmc Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice
    Leif R Lund
    Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, Copenhagen, Denmark
    EMBO J 25:2686-97. 2006
    ....
  39. ncbi Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility
    P A Barber
    Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
    Neurology 56:1015-20. 2001
    ..Thrombolytic therapy for acute stroke (<3 hours) will not have a major impact on death and dependency unless it is accessible to more patients...
  40. ncbi Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke
    Xiaoying Wang
    Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass, USA
    Stroke 35:2726-30. 2004
    Reperfusion therapy with tissue plasminogen activator (tPA) is a rational therapy for acute ischemic stroke. Properly titrated use of tPA improves clinical outcomes...
  41. pmc Neuroprotection for ischemic stroke: two decades of success and failure
    Yu Dennis Cheng
    Stroke Center, University of California School of Medicine, and University of California San Diego, La Jolla, California, 92093 0624, USA
    NeuroRx 1:36-45. 2004
    ..By identifying the discrepancies between preclinical studies and clinical trials, we may be able to set guidelines for future effective trials...
  42. ncbi Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt-PA Registry
    T Nezu
    Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
    Neurology 75:555-61. 2010
    ....
  43. ncbi Very mild stroke patients benefit from intravenous tissue plasminogen activator without increase of intracranial hemorrhage
    Ameer E Hassan
    Department of Neurology and Neurosciences, University Hospital, UMDNJ, Newark, NJ, USA
    South Med J 103:398-402. 2010
    Intravenous recombinant tissue plasminogen activator (IV rt-PA) is an effective medication currently used to treat acute ischemic stroke within three hours of symptom onset in patients with an identifiable clinical deficit measured using ..
  44. ncbi Tissue plasminogen activator -7351C/T enhancer polymorphism is a risk factor for lacunar stroke
    Jim Jannes
    Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville South, South Australia
    Stroke 35:1090-4. 2004
    Occlusive thrombosis is an important component of small- and large-vessel ischemic stroke. Endogenous tissue plasminogen activator (TPA) is the primary mediator of intravascular fibrinolysis and is predominantly expressed by the ..
  45. ncbi Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update
    L Derex
    Service d Urgences Neurovasculaires, Hopital Neurologique, Lyon, France
    J Neurol Neurosurg Psychiatry 79:1093-9. 2008
    ..To minimise the risk of tissue plasminogen activator (tPA) related symptomatic ICH, careful attention must be given to the pre-therapeutic glycaemia value, ..
  46. ncbi A broad-spectrum matrix metalloproteinase inhibitor prevents hemorrhagic complications induced by tissue plasminogen activator in mice
    K Mishiro
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501 1196, Japan
    Neuroscience 205:39-48. 2012
    Delayed activation of tissue plasminogen activator (tPA) can lead to the disruption of the blood-brain barrier (BBB), resulting in hemorrhagic complications...
  47. ncbi A risk score to predict intracranial hemorrhage after recombinant tissue plasminogen activator for acute ischemic stroke
    Brett Cucchiara
    Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    J Stroke Cerebrovasc Dis 17:331-3. 2008
    ..Ability to predict risk of postthrombolysis intracerebral hemorrhage (ICH) is currently limited...
  48. pmc Tissue plasminogen activator activates NF-κB through a pathway involving annexin A2/CD11b and integrin-linked kinase
    Ling Lin
    Division of Nephrology, Department of Medicine, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    J Am Soc Nephrol 23:1329-38. 2012
    ..b>Tissue plasminogen activator (tPA) modulates the NF-κB pathway, but the underlying mechanism remains unknown...
  49. ncbi Tissue-type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity
    Andre L Samson
    Australian Centre for Blood Diseases, Monash University, Level 6 Burnet Building, Alfred Medical Research and Education Precinct, 89 Commercial Road, Prahran 3181, Victoria, Australia
    Neuron 50:673-8. 2006
    ....
  50. pmc Tissue plasminogen activator treatment of stroke in type-1 diabetes rats
    R Ning
    Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, United States
    Neuroscience 222:326-32. 2012
    ..In the present study, we investigated the effects of tissue plasminogen activator (tPA) treatment of stroke in diabetic and non-diabetic rats.
  51. ncbi Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke
    M Ning
    Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Neurology 66:1550-5. 2006
    Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models...
  52. pmc Multipotent mesenchymal stromal cells increase tPA expression and concomitantly decrease PAI-1 expression in astrocytes through the sonic hedgehog signaling pathway after stroke (in vitro study)
    Hongqi Xin
    Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA
    J Cereb Blood Flow Metab 31:2181-8. 2011
    Multipotent mesenchymal stromal cells (MSCs) increase tissue plasminogen activator (tPA) activity in astrocytes of the ischemic boundary zone, leading to increased neurite outgrowth in the brain...
  53. ncbi Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice
    M Takamiya
    Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700 8558, Japan
    Neuroscience 221:47-55. 2012
    ..oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts...
  54. ncbi Recombinant tissue plasminogen activator induces blood-brain barrier breakdown by a matrix metalloproteinase-9-independent pathway after transient focal cerebral ischemia in mouse
    Jean Christophe Copin
    Division of Neurosurgery, University Hospitals of Geneva, Geneva, Switzerland
    Eur J Neurosci 34:1085-92. 2011
    ..Recombinant tissue plasminogen activator (r-tPA) is the only approved thrombolytic treatment of ischemic stroke but r-tPA is potentially ..
  55. ncbi Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression
    Kebin Hu
    Department of Pathology, University of Pittsburgh School of Medicine, S 405 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    J Biol Chem 281:2120-7. 2006
    ....
  56. pmc Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system
    Noreen Bukhari
    Department of Pharmacological Sciences, Stony Brook University, New York, NY 11794 8651, USA
    J Neurosci 31:14931-43. 2011
    ..We report that the clearance of the core protein by the tissue plasminogen activator (tPA)/plasmin proteolytic system partially contributes to ChABC-promoted plasticity...
  57. pmc Subacute intranasal administration of tissue plasminogen activator increases functional recovery and axonal remodeling after stroke in rats
    Zhongwu Liu
    Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA
    Neurobiol Dis 45:804-9. 2012
    As a thrombolytic agent, application of recombinant tissue plasminogen activator (tPA) to ischemic stroke is limited by the narrow time window and side effects on brain edema and hemorrhage...
  58. ncbi Tissue plasminogen activator promotes matrix metalloproteinase-9 upregulation after focal cerebral ischemia
    Kiyoshi Tsuji
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
    Stroke 36:1954-9. 2005
    Thrombolytic therapy with tissue plasminogen activator (tPA) in ischemic stroke is limited by increased risks of cerebral hemorrhage and brain injury...
  59. ncbi Magnetic Resonance Imaging-DRAGON score: 3-month outcome prediction after intravenous thrombolysis for anterior circulation stroke
    Guillaume Turc
    Service de Neurologie, Hopital Sainte Anne, 1 rue Cabanis, 75674 Paris Cedex 14, France
    Stroke 44:1323-8. 2013
    ..showed a high specificity to predict 3-month outcome in patients with acute ischemic stroke treated by intravenous tissue plasminogen activator. We adapted the score for patients undergoing MRI as the first-line diagnostic tool.
  60. ncbi Brain endothelial hemostasis regulation by pericytes
    Jeong Ai Kim
    Department of Neurology, University of California, Irvine, California, USA
    J Cereb Blood Flow Metab 26:209-17. 2006
    ..were physically separated from endothelial cells, pericytes induced significant changes in endothelial tissue plasminogen activator (tPA) messenger ribonucleic acid (mRNA) and protein: tPA mRNA level was decreased in pericyte ..
  61. ncbi Beyond subgroup analysis: improving the clinical interpretation of treatment effects in stroke research
    Mei Lu
    Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI 48202, USA
    J Neurosci Methods 143:209-16. 2005
    ..Results of NINDS t-PA stroke studies confirmed our previous conclusions on the treatment t-PA benefit within 3-h therapeutic window. No subgroup of patients would lead a physician to withhold the t-PA treatment...
  62. ncbi Rapid neurological recovery after intravenous tissue plasminogen activator in stroke: prognostic factors and outcome
    Bejoy Machumpurath
    Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
    Cerebrovasc Dis 31:278-83. 2011
    Treatment with tissue plasminogen activator (tPA) is associated with improved outcome in acute ischemic stroke. Of note, a proportion of patients demonstrate rapid and significant neurological recovery within 24 h...
  63. ncbi Regulation of local availability of active tissue-type plasminogen activator in vivo in man
    T Hrafnkelsdottir
    Clinical Experimental Research Laboratory, Department of Medicine, Sahlgrenska University Hospital Ostra, Sweden
    J Thromb Haemost 2:1960-8. 2004
    ..Despite a molar excess of PAI-1, the majority of tPA released during stimulation does not undergo local inactivation. The capacity to release tPA locally cannot be predicted from its plasma concentration...
  64. pmc Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice
    Annika Jögi
    Finsen Laboratory, Copenhagen University Hospital, Copenhagen Biocenter, Copenhagen, Denmark
    PLoS ONE 5:e12746. 2010
    ..In contrast, individual genetic deficiencies in either uPA or tPA lead to wound healing kinetics with no or only slightly delayed closure of skin wounds...
  65. ncbi The role of endogenous versus exogenous tPA on edema formation in murine ICH
    Ruth Thiex
    Department of Neurosurgery, Aachen University, Aachen, Germany
    Exp Neurol 189:25-32. 2004
    ..evolved evacuating the hematoma by stereotaxic injection of a fibrinolytic agent such as recombinant tissue plasminogen activator (rtPA), followed by aspiration of the lysed clot...
  66. ncbi Informed consent for thrombolytic therapy for patients with acute ischemic stroke treated in routine clinical practice
    Julie R Rosenbaum
    Department of Internal Medicine, Yale University School of Medicine, West Haven, Conn, USA
    Stroke 35:e353-5. 2004
    Little is known about informed consent for tissue plasminogen activator (tPA)...
  67. ncbi The JNK inhibitor XG-102 protects from ischemic damage with delayed intravenous administration also in the presence of recombinant tissue plasminogen activator
    Karine Wiegler
    Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Suisse
    Cerebrovasc Dis 26:360-6. 2008
    ..We also tested the compatibility of the compound with recombinant tissue plasminogen activator (rtPA), commonly used for intravenous thrombolysis and known to enhance excitotoxicity.
  68. ncbi Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion
    Ivo G Schoots
    Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands
    Thromb Haemost 91:497-505. 2004
    ..Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-I by administration of MA-33H1F7...
  69. pmc Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects
    Zaid Al-Hamodi
    Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
    Cardiovasc Diabetol 10:23. 2011
    Increased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of ..
  70. pmc Annexin A2 combined with low-dose tPA improves thrombolytic therapy in a rat model of focal embolic stroke
    Haihao Zhu
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 30:1137-46. 2010
    Recent studies showed that soluble annexin A2 dramatically increases tissue plasminogen activator (tPA)-mediated plasmin generation in vitro, and reduces thrombus formation in vivo...
  71. ncbi Body temperature and response to thrombolytic therapy in acute ischaemic stroke
    M Millan
    Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
    Eur J Neurol 15:1384-9. 2008
    To determine the relationship between body temperature (BT), arterial recanalization, functional outcome, and hemorrhagic transformation (HT) of cerebral infarction in patients treated with i.v. tissue plasminogen activator (tPA).
  72. pmc Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis
    Maarten G Lansberg
    Stanford Stroke Center, Stanford University Medical Center, Palo Alto, CA 94304 9705, USA
    Stroke 40:2438-41. 2009
    ..European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window...
  73. pmc Normobaric hyperoxia reduces the neurovascular complications associated with delayed tissue plasminogen activator treatment in a rat model of focal cerebral ischemia
    Wenlan Liu
    College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA
    Stroke 40:2526-31. 2009
    A major limitation of tissue plasminogen activator (tPA) thrombolysis for ischemic stroke is the narrow time window for safe and effective therapy...
  74. ncbi Thrombolytic therapy with recombinant tissue plasminogen activator for acute ischemic stroke: where do we go from here? A cumulative meta-analysis
    J M Wardlaw
    Department of Clinical Neurosciences, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK
    Stroke 34:1437-42. 2003
    Recombinant tissue plasminogen activator (rtPA; Actilyse) is not as widely used in clinical practice as it could be. Have new data since 1995 strengthened the evidence sufficiently to justify more widespread use of rtPA?
  75. ncbi A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke
    E Clarke Haley
    Department of Neurology, University of Virginia Health System, Charlottesville, VA, USA
    Stroke 36:607-12. 2005
    ..This open-label, dose-escalation safety study was conducted to develop initial experience with TNK in the treatment of ischemic stroke...
  76. ncbi Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush
    Lisa B Siconolfi
    Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Neurosci Res 74:430-4. 2003
    ..These findings show that the PAs are important for MMP-9 and MMP-2 activity at the crush site...
  77. ncbi Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke
    W M Clark
    Oregon Stroke Center, Portland 97201, USA
    JAMA 282:2019-26. 1999
    ..This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset...
  78. ncbi Tissue-type plasminogen activator: a historical perspective and personal account
    D Collen
    Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
    J Thromb Haemost 2:541-6. 2004
    ..Genetically modified variants of t-PA have been developed for bolus administration in patients with AMI...
  79. ncbi NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity
    A Baron
    INSERM U, Cyceron, University of Caen Basse Normandie, Caen, France
    Cell Death Differ 17:860-71. 2010
    ..This study shows that the earlier described pro-neurotoxic effect of tPA is mediated by NR2D-containing NMDAR-dependent extracellular signal-regulated kinase activation, a deleterious effect prevented by synaptic pre-activation...
  80. ncbi Safety profile of tissue plasminogen activator treatment among stroke patients carrying a common polymorphism (C-1562T) in the promoter region of the matrix metalloproteinase-9 gene
    Joan Montaner
    Neurovascular Research Laboratory, Stroke Unit, Vall d Hebron Hospital, Barcelona, Spain
    Stroke 34:2851-5. 2003
    ..barrier disruption, has been implicated in the appearance of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment in stroke patients...
  81. ncbi Thrombolysis for acute stroke in routine clinical practice
    Dawn M Bravata
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8025, USA
    Arch Intern Med 162:1994-2001. 2002
    ....
  82. pmc Recapture after exocytosis causes differential retention of protein in granules of bovine chromaffin cells
    David Perrais
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 3098, USA
    J Physiol 560:413-28. 2004
    ..Here we compare the exocytic release of fluorescently labelled neuropeptide Y (NPY) and tissue plasminogen activator from single granules...
  83. ncbi Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASS-II trial
    Mei Yong
    Department of Statistics in Medicine, Heinrich Heine University Hospital, Duesseldorf, Germany
    Stroke 39:2749-55. 2008
    ..Baseline hyperglycemia has been considered an independent predictor of stroke outcome. The present study analyzes the dynamics of serum glucose levels within the first 24 hours and its impact on stroke outcome...
  84. ncbi Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin
    Z L Chen
    Department of Pharmacology, University at Stony Brook, New York 11794 8651, USA
    Cell 91:917-25. 1997
    ..excitatory amino acids can provoke neuronal death in the hippocampus, and the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) have been implicated in this death...
  85. ncbi Fibrinolysis: the key to new pathogenetic mechanisms
    Esther Zorio
    Hospital Universitario La Fe, Centro de Investigacion, Servicio de Cardiología y Servicio de Ginecología Valencia, Spain
    Curr Med Chem 15:923-9. 2008
    ....
  86. ncbi Does the National Institutes of Health Stroke Scale favor left hemisphere strokes? NINDS t-PA Stroke Study Group
    D Woo
    Department of Neurology, University of Cincinnati, Cincinnati, Ohio 45220, USA
    Stroke 30:2355-9. 1999
    ..Of 42 possible points, 7 points are directly related to measurement of language compared with only 2 points related to neglect...
  87. ncbi Gene polymorphism of t-PA is associated with forearm vascular release rate of t-PA
    C Jern
    Clinical Experimental Research Laboratory, Heart and Lung Institute, and Department of Neurology, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Goteborg University, Sweden
    Arterioscler Thromb Vasc Biol 19:454-9. 1999
    ..The relationship is not reflected by circulating steady-state plasma levels and can thus not be disclosed by conventional venous plasma sampling...
  88. ncbi Stroke research priorities for the next decade--A representative view of the European scientific community
    Stephen Meairs
    Neurologische Klinik, Ruprecht Karls Universitat Heidelberg, Theodor Kutzer Ufer, DE 68135 Mannheim Germany
    Cerebrovasc Dis 22:75-82. 2006
  89. pmc Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator
    T H Bugge
    Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 93:5899-904. 1996
    ....
  90. ncbi Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors
    Maarten G Lansberg
    Stanford University, Stanford Stroke Center, Palo Alto, CA 94304, USA
    Cerebrovasc Dis 24:1-10. 2007
    ....
  91. ncbi Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator
    Xiaoying Wang
    Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital, Charlestown, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 9:1313-7. 2003
    Although thrombolysis with tissue plasminogen activator (tPA) is a stroke therapy approved by the US Food and Drug Administration, its efficacy may be limited by neurotoxic side effects...
  92. ncbi Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats
    Toshihisa Sumii
    Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA
    Stroke 33:831-6. 2002
    Thrombolytic therapy with tissue plasminogen activator (tPA) for acute ischemic stroke remains complicated by risks of hemorrhagic transformation...
  93. pmc Inhibition of p75 neurotrophin receptor attenuates isoflurane-mediated neuronal apoptosis in the neonatal central nervous system
    Brian P Head
    Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA
    Anesthesiology 110:813-25. 2009
    ..proBDNF is cleaved into mature BDNF (mBDNF) by plasmin, a protease converted from plasminogen by tissue plasminogen activator (tPA) that is released with neuronal activity; mBDNF supports survival and stabilizes synapses through ..
  94. ncbi Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity
    Petti T Pang
    Section on Neural Development and Plasticity, Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development NICHD, Bethesda, MD 20892, USA
    Science 306:487-91. 2004
    ..Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their ..
  95. ncbi Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study
    A R Folsom
    Division of Epidemiology, School of Public Health, University of Minnesota, MN 55454-1015, USA
    Arterioscler Thromb Vasc Biol 21:611-7. 2001
    ..of middle-aged adults, we examined the association of incident CHD with several fibrinolytic factors: tissue plasminogen activator antigen, plasminogen activator inhibitor-1, plasminogen, and fibrin fragment D-dimer as well as a ..
  96. ncbi Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice
    N Nagai
    Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Center for Molecular and Vascular Biology, KU Leuven, Belgium
    Circulation 99:2440-4. 1999
    ....
  97. ncbi The human tissue plasminogen activator-Cre mouse: a new tool for targeting specifically neural crest cells and their derivatives in vivo
    Thomas Pietri
    UMR 144 Compartimentation et Dynamique Cellulaire Centre National de la Recherche Scientifique et Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Dev Biol 259:176-87. 2003
    ..We have established a new transgenic line expressing the Cre recombinase under the control of the human tissue plasminogen activator promoter (Ht-PA)...
  98. ncbi Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke
    P A Lapchak
    Department of Neuroscience, University of California at San Diego, La Jolla 92093 0624, USA
    Stroke 31:3034-40. 2000
    A potentially dangerous side effect associated with tissue plasminogen activator (tPA) use is cerebral hemorrhage. We have focused on developing drugs that could be administered with tPA to reduce the rate of hemorrhage...
  99. ncbi Age-related differences in characteristics, performance measures, treatment trends, and outcomes in patients with ischemic stroke
    Gregg C Fonarow
    Ahmanson UCLA Cardiomyopathy Center, UCLA Medical Center, 10833 LeConte Ave, Room 47 123 CHS, Los Angeles, CA 90095 1679, USA
    Circulation 121:879-91. 2010
    ..We sought to examine age-related differences in characteristics, performance measures, temporal trends, and early clinical outcomes for acute ischemic stroke in a large contemporary cohort...
  100. ncbi Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II
    Chia Jen Siao
    Department of Pharmacological Sciences and Program in Molecular and Cellular Pharmacology, University Medical Center at Stony Brook, Stony Brook, New York 11794 8651, USA
    J Neurosci 22:3352-8. 2002
    ..One molecule whose expression is upregulated after excitotoxic injury is tissue plasminogen activator (tPA), a serine protease with dual roles in the CNS...
  101. ncbi Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain
    Toru Yamashita
    Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    J Cereb Blood Flow Metab 29:715-25. 2009
    In the ischemic brain, reperfusion with tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT); however, the mechanism remains elusive...

Research Grants68

  1. Antiphospholipid antibodies and lupus: new molecular targets for treatment
    Emilio B Gonzalez; Fiscal Year: 2013
    ..There is strong evidence that annexin A2, a receptor for tissue plasminogen activator (tPA) and plasminogen, and toll-like receptor 4 (TLR-4), a receptor for bacterial lipopolysaccharide (..
  2. MRI of Acute Vascular Injury and Hemorrhagic Transformation in Ischemic Stroke
    Robert A Knight; Fiscal Year: 2010
    ..Thrombolytic therapy with tissue plasminogen activator (tPA) acts to increase blood flow to the ischemic tissue and is the only approved treatment for acute ..
  3. Treatment of stroke with a clinically approved proteasome inhibitor
    Li Zhang; Fiscal Year: 2012
    ..Thrombolysis with tissue plasminogen activator (tPA) promotes adverse vascular events that limit the therapeutic window of stroke to three hours...
  4. Adjunctive Use of Apyrase to Fibrinolytic Therapy
    Ridong Chen; Fiscal Year: 2013
    ..The current regimen, including tissue plasminogen activator, aspirin, clopidogrel and heparin, still induces inadequate coronary reperfusion in 30-40% of patients ..
  5. Plasminogen activators and NMDA after brain injury
    William M Armstead; Fiscal Year: 2012
    ..Urokinase and tissue plasminogen activator (uPA and tPA) are serine proteases whose contributions to the regulation of cerebral hemodynamics are ..
  6. S-Nitrosylated Hemoglobin and Ischemic Brain Injury
    David Warner; Fiscal Year: 2010
    ..It is known from humans treated with tissue plasminogen activator that ischemic tissue can be salvaged from infarction by thrombolytic CBF restoration...
  7. Investigation of underlying mechanisms of sex differences in cerebral ischemia
    Chad S Siegel; Fiscal Year: 2010
    ..Currently, there is only one FDA-approved treatment for stroke;Tissue Plasminogen Activator, which can lead to severe brain hemorrhage in up to 7% of treated patients...
  8. Renin-angiotensin and fibrinolysis interaction in humans
    NANCY JOAN BROWN; Fiscal Year: 2013
    ..nitric oxide increases muscle glucose uptake in humans;however, nitric oxide also decreases vascular tissue plasminogen activator release through a cGMP-independent mechanism...
  9. Endogenous and exogenous protection of the BBB in stroke
    Richard F Keep; Fiscal Year: 2013
    ..g. hemorrhagic transformation is a major limiting factor for the use of tissue plasminogen activator-induced reperfusion therapy for ischemic stroke)...
  10. Mini-plasmin: Pre-Clinical Evaluation of a Novel Thrombolytic Strategy for Stroke
    Irina Y Sazonova; Fiscal Year: 2012
    ..Despite the testing of over 70 agents in clinical trials, only one drug, the recombinant tissue plasminogen activator (TPA), has been approved by the FDA for the treatment of ischemic stroke...
  11. Ac-SDKP for Treatment of Acute Stroke
    Zheng Gang Zhang; Fiscal Year: 2013
    ..b>Tissue plasminogen activator (tPA) is the only drug approved by the Food and Drug Administration (FDA) for treatment of acute stroke ..
  12. Transcranial Sonothrombolysis with Diagnostic Ultrasound
    Thilo Hoelscher; Fiscal Year: 2013
    ..contrast agents (UCA) potentiate the effect of sonothrombolysis, without or in combination with tissue Plasminogen Activator (tPA)...
  13. Role of Hyperglycemia in Intracerebral Hemorrhage
    Edward P Feener; Fiscal Year: 2013
    ..and long-term mortality, occurrence of symptomatic ICH in stroke patients treated with intravenous tissue plasminogen activator (tPA), and increased hematoma volume and expansion, which are significant and independent determinants ..
  14. Weibel-Palade Bodies: roles in thrombosis, inflammation and stroke
    Denisa D Wagner; Fiscal Year: 2013
    ..a) VWF and ADAMTS13 in stroke, b) Therapeutic effect of rADAMTS13 in ischemic stroke and comparison to tissue plasminogen activator (tPA). The application heavily relies on genetically modified mice, all available to our laboratory...
  15. Vascular protection by epoxide hydrolase inhibition in cerebral ischemia
    Alexis N Simpkins; Fiscal Year: 2010
    ..Although thrombolysis with tissue plasminogen activator is the only treatment for ischemic stroke, most patients are not candidates for receiving thrombolysis ..
  16. Novel Methods for Dissolving Blood Clots
    GUY LELAND REED; Fiscal Year: 2013
    ..b>Tissue plasminogen activator (TPA) and other blood clot-dissolving drugs are better at preventing post-thrombotic symptoms, but the ..
  17. US-China Collaborative Research on Stroke Imaging
    Jinyuan Zhou; Fiscal Year: 2013
    ..Currently, the only FDA- approved treatment for ischemic stroke is intravenous tissue plasminogen activator (IV tPA) that is given within three hours of symptom onset...
  18. Pulmonary Formulation of tPA for Plastic Bronchitis
    Kathleen A Stringer; Fiscal Year: 2010
    ..Presently, PB is anecdotally treated with inhaled tissue plasminogen activator (tPA) with no evidence for safety or efficacy...
  19. Molecular pathogenesis of alpha-tocopherol associated neuroaxonal dystrophy in an
    Carrie Finno; Fiscal Year: 2013
    ..Experience using mouse model will enhance Dr. Finno's future research potential. Five years of mentored support is requested. ..
  20. Ultrasound assisted thrombolysis for acute pulmonary embolism
    CURTIS GENSTLER; Fiscal Year: 2012
    ..At the end of therapy, time to lysis determined angiographically will be used to determine bioefficacy. ..
  21. The Role of Tissue Plasminogen Activator in a Mouse Spinal Cord Injury Model
    Noreen Bukhari; Fiscal Year: 2012
    ..We hypothesize that these events are dependent upon DARPP-32 expression. ..
  22. Stroke Therapy
    VINOD D LABHASETWAR; Fiscal Year: 2013
    ..Intravenous administration of tissue plasminogen activator (t-PA) is the only FDA-approved therapy to re-establish cerebral blood flow...
  23. Real-time Monitoring of cerebral tissue oxygen in ischemic stroke
    Nadeem Khan; Fiscal Year: 2013
    ..the validity of the method by correlating with outcome when blood flow is restored by recombinant tissue plasminogen activator (rtPA). We will test the hypothesis by using the proposed implantable resonator-based EPR oximetry...
  24. Mac-1 coordinates PDGF-CC activation by microglia and promotes BBB opening
    Li Zhang; Fiscal Year: 2013
    ..The majority of strokes are caused by the blockade of blood vessels (ischemic stroke). Currently, tissue plasminogen activator (tPA) is the only thrombolytic drug approved by FDA for the treatment of ischemic stroke...
  25. Mechanism of thrombolytic tPA induced intracerebral hemorrhage after stroke
    Daniel A Lawrence; Fiscal Year: 2013
    ..Thrombolytic therapy with tissue plasminogen activator (tPA) is the only approved treatment for ischemic stroke, but its use carries a significant risk for ..
  26. Neuronal Regeneration of Stroked Brain with Perlecan Domain V
    GREGORY JAYE BIX; Fiscal Year: 2013
    ..is still a critical need for new ischemic stroke therapies to reduc this significant societal burden as tissue plasminogen activator (t-PA), the only FDA approved ischemic stroke pharmaceutical therapy, has a limited therapeutic window ..
  27. Neurorestorative therapy of stroke with HUCBC in T2DM rats
    Jieli Chen; Fiscal Year: 2013
    ..Treatment of stroke with tissue plasminogen activator (rtPA) at 2-3 hours after stroke decreases lesion volume in non-DM rats...
  28. Acute Stroke Program of Interventions: Racial &Ethnic Disparities(ASPIRE)
    CHELSEA M KIDWELL; Fiscal Year: 2011
    ..Several studies have suggested that blacks are less likely than whites to receive intravenous tissue plasminogen activator (IV tPA), the only FDA-approved acute ischemic stroke therapy...
  29. Field Administration of Stroke Therapy-Magnesium Trial (FAST-MAG)
    Jeffrey L Saver; Fiscal Year: 2013
    ..patient subgroups, including patients with ischemic stroke, ischemic stroke co-treated with tissue plasminogen activator, ischemic stroke not co-treated with tissue plasminogen activator, intracerebral hemorrhage, patients ..
  30. Establishment of fast pH MRI for imaging metabolic injury during acute stroke
    Phillip Zhe Sun; Fiscal Year: 2013
    ..Whereas FDA-approved tissue plasminogen activator (tPA) is a potent thrombolytic agent for treating acute ischemic stroke, few patients present for ..
  31. tPA, white matter and cell therapy for stroke
    Yi Li; Fiscal Year: 2013
    ..outgrowth after stroke is enhanced by MSC treatment via astrocytic increase in the net activity of tissue plasminogen activator (tPA) via modifying the balance of tPA/plasminogen activator inhibitor-1(PAI-1) level...
  32. Annexin 2 in Lymphoproliferative Angiogenesis
    Jia Ruan; Fiscal Year: 2012
    ..Annexin 2 (A2) is a fibrinolytic protease receptor that binds plasminogen and tissue plasminogen activator (tPA) at the surface of endothelial cells and monocyte/macrophages...
  33. Ultrasound application in treatment of intra-cranial hemorrhage
    DOUGLAS R HANSMANN; Fiscal Year: 2010
    ..The project holds the potential of reducing healthcare costs in treatment of intracranial hemorrhage and bringing benefits to patients &clinicians. ..
  34. A Novel Intervention Strategy for Stroke with RTL Therapy
    Halina Offner; Fiscal Year: 2013
    ..Finally, 3) that RTL1000 is an effective therapy when combined with tissue plasminogen activator (tPA)...
  35. 2010 Gordon Research Conference on Plasminogen Activation and Ertracellular Prote
    Bradford S Schwartz; Fiscal Year: 2010
    ..Previous research in this area has led to the development of tissue plasminogen activator for the successful treatment of a wide range of thromboembolic disorders...
  36. Imaging Study of Combination Thrombolytic Therapy
    GEORGE JEROME SHAW; Fiscal Year: 2010
    ..Currently, the only FDA approved therapy is the administration of tissue plasminogen activator (tPA) within 3 hours of stroke onset...
  37. Factor XI Inhibition for the Treatment of Ischemic Stroke
    ERIK IAN TUCKER; Fiscal Year: 2012
    ..Since 14E11 is not expected to produce bleeding side-effects, this approach has the potential to provide a safe alternative or addition to other more dangerous antithrombotic treatments. ..
  38. Therapeutic thrombin analogs
    ERIK IAN TUCKER; Fiscal Year: 2011
    ..Existing antithrombotic and thrombolytic drugs, such as recombinant tissue plasminogen activator (TPA) cause bleeding and, thus, cannot be used at their fully effective doses...
  39. Biomarkers of Vascular Disease Progression in Type 1 Diabetes Mellitus
    Maria F Lopes-Virella; Fiscal Year: 2011
    ..fibrinolytic and clotting system - fibrinogen, plasminogen activator inhibitor-1 and tissue plasminogen activator. We will assay these biomarkers longitudinally in samples, obtained from the well characterized DCCT/..
  40. Clot Lysis: Evaluating Accelerated Resolution of IVH Phase III (CLEAR III)
    Daniel F Hanley; Fiscal Year: 2013
    ..Adding recombinant tissue plasminogen activator (rt-PA) may be the key to a rapid, effective, and safe means for blood removal that limits brain tissue ..
  41. Identification of PKC delta Substrates in Stroke-reperfusion Injury
    Wen Hai Chou; Fiscal Year: 2009
    ..Thrombolytic agents such as tissue plasminogen activator (t-PA) are currently the only drugs available to reverse acute ischemic stroke, but reestablishment of ..
  42. A Novel Ultrasound Phased Array and Sonication Method for Stroke Treatments
    Kullervo Hynynen; Fiscal Year: 2012
    ..of patients that will have recanalization of the occluded vessel when administrated together with tissue plasminogen activator (tPA)...
  43. Novel NMDA Antagonists to Treat Stroke
    Bhaumik B Patel; Fiscal Year: 2013
    ..provided by applicant): Acute ischemic stroke is now a treatable condition with the thrombolytic, tissue plasminogen activator (tPA)...
  44. Impact of Regionalization of Care in Acute Stroke Patients
    Prasanthi Govindarajan; Fiscal Year: 2013
    ..Thrombolysis with intravenous tissue plasminogen activator (IV t-PA) remains the only proven treatment for acute ischemic stroke who present within three hours of ..
  45. Who Benefits from tPA 3-6 hours after Stroke
    Maarten G Lansberg; Fiscal Year: 2010
    Currently, the only FDA approved treatment for acute stroke is intravenous tissue plasminogen activator (iv tPA) administered within three hours after symptom onset...
  46. Workshop on the Molecular and Cellular Biology of Plasminogen Activation
    Victoria Ploplis; Fiscal Year: 2013
    ..important for the development of new therapies in the field of hemostasis, including recombinant tissue plasminogen activator, thrombolytics, and anti-thrombolytics...
  47. MSCs Induce Brain Plasticity via tPA
    Michael Chopp; Fiscal Year: 2013
    ..We propose that when administered after stroke, MSCs activate tissue plasminogen activator (tPA) within parenchymal cells, and tPA mediates neurite remodeling leading to improvement in ..
  48. Proteases in IOP-mediated glaucomatous damage
    Shravan K Chintala; Fiscal Year: 2010
    ..This application will test the hypothesis that proteases, tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), up-regulated by elevated IOP cause RGC loss and ..
  49. Development of Stroke Point of Care Immunoassay for Cellular Fibronectin
    Albert K Man; Fiscal Year: 2010
    ..For ischemic stroke, which comprises approximately four-fifths of all strokes, thrombolytic therapy by tissue plasminogen activator (tPA) has been proven to be effective in the critical first 3 hours from symptom onset...
  50. A Community Partnership to Treat Stroke
    LESLI ELIZABETH SKOLARUS; Fiscal Year: 2013
    ..Excellent resources of a top university and a mentoring team with demonstrated success in developing junior investigators in these topic areas makes the University of Michigan an ideal environment for this project. ..
  51. Thrombolysis in Pediatric Stroke Study (TIPS)
    Catherine M Amlie-Lefond; Fiscal Year: 2013
    ..study is phase I study which will establish the safety, dosing and pharmacokinetics of intravenous (tissue plasminogen activator) tPA for childhood stroke...
  52. 2012 Gordon Research Conference and Gordon-Kenan Research Seminar on Plasminogen
    Bradford S Schwartz; Fiscal Year: 2011
    ..Previous research in this area has led to the development of tissue plasminogen activator for the successful treatment of a wide range of thromboembolic disorders, and the discovery of ..
  53. Ultrasound-Assisted Thrombolysis for Stroke Therapy
    Christy K Holland; Fiscal Year: 2012
    Combined ultrasound and tissue plasminogen activator (rt-PA) therapy, or sonothrombolysis, has been shown to improve recanalization in patients with acute ischemic stroke...
  54. Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza
    DAVID SIGMUND LIEBESKIND; Fiscal Year: 2013
    ..impairs recanalization and reperfusion with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans...
  55. Phenylpropanoid Analogs to Treat Stroke
    Paul A Lapchak; Fiscal Year: 2012
    ..ischemic stroke resulting from an embolism is now a treatable condition, because thrombolysis with tissue plasminogen activator (tPA) has been approved by the FDA...
  56. Discovery of ubiquitin ligase substrates - the development of integrated experime
    Timothy W Randolph; Fiscal Year: 2010
    ..We will develop cutting-edge experimental and computational technologies to identify the substrate cohorts for any desired ubiquitin ligase, especially those implicated in human diseases such as cancer and neurodegenerative disorders. ..
  57. PLATELETS, PLATELET AGGREGATES & PLASMINOGEN ACTIVATION
    Joseph Loscalzo; Fiscal Year: 1991
    ..We have demonstrated in preliminary work that tissue plasminogen activator added to platelets induced to aggregate in plasma facilitates dispersal of the aggregates, or ..
  58. Reducing Stroke by a Novel, Clot-dissolving Antibody
    GUY LELAND REED; Fiscal Year: 2013
    ..b>Tissue plasminogen activator (TPA), an agent that catalyzes the dissolution of blood clots, is the only effective, FDA-approved ..
  59. BIOMEDICAL (BASIC)
    Nancy R Cook; Fiscal Year: 2009
    ..in the Framingham and Reynolds models, including lipoprotein-associated phospholipase A2 (Lp-PLA), tissue plasminogen activator (tPA antigen), and amino-terminal pro-B-type natriuretic peptide (proBNP), In addition, we will refine ..
  60. ENDOTHELIAL CELL DIVERSITY DURING FETAL DEVELOPMENT
    Eugene Levin; Fiscal Year: 2001
    ..Using tissue plasminogen activator (tPA) expression as an endothelial cell marker, we have found a pattern of progressive and transitory ..
  61. STRUCTURE/FUNCTION STUDIES ON PLASMINOGEN AND PLASMIN
    Francis Castellino; Fiscal Year: 1999
    ..enzymology, immunochemistry, spectroscopic properties and molecular biology of human plasminogen, tissue plasminogen activator, urokinase, streptokinase and fibrin(ogen)...
  62. Translation of pH-weighted MRI to Image Human Acute Stroke
    ALMA SORENSEN; Fiscal Year: 2009
    ..For instance, the conventional treatment window for recombinant tissue plasminogen activator (tPA) is within 3 hrs of stroke onset, which significantly limits its clinical applications...
  63. Cardiovascular Effects of Scutellaria baicelensis
    Chun Su Yuan; Fiscal Year: 2002
    ..separate studies, we observed that quercetin, a plant flavonoid, inhibited endothelin-1 and stimulated tissue plasminogen activator in vascular endothelial cells...
  64. WOUND HEALING ANGIOGENESIS
    Frank Isik; Fiscal Year: 2002
    ..include the plasminogen activator system, which consists of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), balanced by plasminogen activator inhibitor-1 (PAI-1), which limits plasmin generation and ..
  65. DIFFERENTIALLY EXPRESSED GENES IN PRIMARY BREAST CANCER
    ARTHUR PARDEE; Fiscal Year: 1999
    ..protease inhibitor) acts as a tumor suppressor through its interaction with the serine protease, tissue plasminogen activator. The structure of maspin, deduced from its sequence, does not support a strong prediction concerning ..
  66. DDAVP IN CONGENITAL PLATELET FUNCTION DISORDERS
    A Rao; Fiscal Year: 1990
    ..factor VIII-related antigen, factor VIII-von Willebrand factor/ristocetin cofactor activity and tissue plasminogen activator (t-PA) in well-characterized patients with congenital platelet function defects, excluding vWD, and 2) ..
  67. ENHANCING THROMBOLYSIS BY INHIBITION OF A2-ANTIPLASMIN
    Guy Reed; Fiscal Year: 1993
    ..By inhibiting alpha2AP this antibody is synergistic with tissue plasminogen activator (t-PA) in clot lysis; at the same time, it increases the specificity of t-PA for fibrinolysis...
  68. THROMBOLYSIS IN MYOCARDIAL ISCHEMIA COORDINATING CENTER
    Genell Knatterud; Fiscal Year: 1992
    ..TIMI III A is a double-blind comparison of recombinant tissue plasminogen activator (t-PA) to placebo for improvement of coronary artery stenosis and perfusion...