Vampire Bat Salivary Plasminogen Activator (Desmoteplase): A Unique Fibrinolytic Enzyme That Does Not Promote Neurodegeneration

  title={Vampire Bat Salivary Plasminogen Activator (Desmoteplase): A Unique Fibrinolytic Enzyme That Does Not Promote Neurodegeneration},
  author={Gabriel T. Liberatore and Andr{\'e} L. Samson and Christopher F. Bladin and Wolf-Dieter Schleuning and Robert L. Medcalf},
  journal={Stroke: Journal of the American Heart Association},
Background and Purpose— Tissue-type plasminogen activator (tPA) promotes excitotoxic and ischemic injury within the brain. These findings have implications for the use of tPA in the treatment of acute ischemic stroke. The plasminogen activator from vampire bat (Desmodus rotundus) saliva (D rotundus salivary plasminogen activator [DSPA]; desmoteplase) is an effective plasminogen activator but, in contrast to tPA, is nearly inactive in the absence of a fibrin cofactor. The purpose of this study… 

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Vampire Bat Salivary Plasminogen Activator (Desmoteplase) Inhibits Tissue-Type Plasminogen Activator-Induced Potentiation of Excitotoxic Injury
Intravenous treatment with tPA promotes excitotoxic injury, raising the possibility that leakage of tPA from the vasculature into the parenchyma contributes to brain damage.
Recombinant Desmodus rotundus Salivary Plasminogen Activator Crosses the Blood–Brain Barrier Through a Low-Density Lipoprotein Receptor-Related Protein-Dependent Mechanism Without Exerting Neurotoxic Effects
It is shown that desmoteplase crosses the blood–brain barrier but does not promote neuronal death, and intravenous administration of desmotesplase antagonizes the neurotoxicity induced by vascular rtPA.
The Neurotoxicity of Tissue Plasminogen Activator?
Methods of neuroprotection, which prevent tPA toxicity or additional mechanical means to open cerebral vessels, are now needed to prevent neurotoxic effects of this exogenous tPA.
Bat Plasminogen Activator: Desmoteplase – From Bat to Bench to Bedside of Stroke Victims
This work has confirmed an extremely high fibrin specificity and a potential for a lower bleeding propensity, demonstrated in a variety of preclinical studies on DSPA, which distinguishes it from rt-PA, which, apart from clot lysis, has a number of additional physiological roles.
Tissue-type plasminogen activator is a neuroprotectant in the central nervous system
  • M. Yepes
  • Biology
    Front. Cell. Neurosci.
  • 2015
The postulated neurotoxic effect of tPA needs to be reconsidered and instead indicate the emergence of a new paradigm: that tPA is an endogenous neuroprotectant in the central nervous system (CNS).
Vampire Bats Yield Potent Clot Buster for Ischemic Stroke
DSPA may offer another therapeutic option instead of tPA, a current therapy for stroke, as it has not been associated with the systemic plasminogen consumption and fibrinogenolysis that potentially may occur in those receiving tPA.
Inhibition of Desmoteplase-Induced Fibrinolytic Activity In Vitro
The effect of aprotinin and D-Phe-Pro-Arg-chloromethylketone (PPACK) on desmoteplase-induced fibrinolysis is investigated and significant generation of plasmin-antiplasmin complex was observed.
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An up-to-date overview of the current knowledge on the enzymatic or cytokine-like effects of action of tPA in the CNS, its various molecular substrates or receptors is provided, focusing on the processes occurring during and after ischemic or hemorrhagic stroke.
Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase
Data from “The desmoteplase in Acute Ischemic Stroke” trials suggest that the drug is well tolerated and its safety profile is comparable to placebo, and may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window.
Impacts of tissue-type plasminogen activator (tPA) on neuronal survival
A synthetic snapshot of the current knowledge regarding the natural history of tPA is provided and how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival is discussed.


Structural Features Mediating Fibrin Selectivity of Vampire Bat Plasminogen Activators (*)
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Tissue plasminogen activator (tPA) increase neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice
Since tPA promotes desirable as well as undesirable outcomes during stroke, future therapies should be aimed at countering the excitotoxic damage of tPA to afford even better neuropro-tection after an acute cerebral infarct.
Tissue plasminogen activator (tPA) deficiency exacerbates cerebrovascular fibrin deposition and brain injury in a murine stroke model: studies in tPA-deficient mice and wild-type mice on a matched genetic background.
It is indicated that tPA deficiency exacerbates ischemia-induced cerebrovascular thrombosis and that endogenous tPA protects the brain from an ischemic insult, presumably through its thrombolytic action.
The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling
It is reported for the first time that t-PA potentiates signaling mediated by glutamatergic receptors by modifying the properties of the N-methyl-D-aspartate (NMDA) receptor.
Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice.
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Fibrin selectivity of the isolated protease domains of tissue-type and vampire bat salivary gland plasminogen activators.
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Tissue plasminogen activator does not increase neuronal damage in rat models of global and focal ischemia
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Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator.
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An Extracellular Proteolytic Cascade Promotes Neuronal Degeneration in the Mouse Hippocampus
Infusion of inhibitors of the extracellular tPA/plasmin proteolytic cascade into the hippocampus protects neurons against excitotoxic injury, suggesting a novel strategy for intervening in neuronal degeneration.