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Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator

Tissue plasminogen activator (tPA) thrombolysis continues to be the gold standard therapy for ischemic stroke. Due to the time-limited treatment window, within 4.5 h of stroke onset, and a variety of potentially deadly complications related to delayed administration, particularly hemorrhagic transfo...

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Autores principales: Knecht, Talia, Borlongan, Cesar, dela Peña, Ike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187940/
https://www.ncbi.nlm.nih.gov/pubmed/30450415
http://dx.doi.org/10.4103/bc.bc_21_18
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author Knecht, Talia
Borlongan, Cesar
dela Peña, Ike
author_facet Knecht, Talia
Borlongan, Cesar
dela Peña, Ike
author_sort Knecht, Talia
collection PubMed
description Tissue plasminogen activator (tPA) thrombolysis continues to be the gold standard therapy for ischemic stroke. Due to the time-limited treatment window, within 4.5 h of stroke onset, and a variety of potentially deadly complications related to delayed administration, particularly hemorrhagic transformation (HT), clinical use of tPA is limited. Combination therapies with other interventions, drug or nondrug, have been hypothesized as a logical approach to enhancing tPA effectiveness. Here, we discuss various potential pharmacological and nondrug treatments to minimize adverse effects, primarily HT, associated with delayed tPA administration. Pharmacological interventions include many that support the integrity of the blood–brain barrier (i.e., atorvastatin, batimastat, candesartan, cilostazol, fasudil, and minocycline), promote vascularization and preserve cerebrovasculature (i.e., coumarin derivative IMM-H004 and granulocyte-colony stimulating factor), employing other mechanisms of action (i.e., oxygen transporters and ascorbic acid). Nondrug treatments are comprised of stem cell transplantation and gas therapies with multi-faceted approaches. Combination therapy with tPA and the aforementioned treatments demonstrated promise for mitigating the adverse complications associated with delayed tPA treatment and rescuing stroke-induced behavioral deficits. Therefore, the conjunctive therapy method is a novel therapeutic approach that can attempt to minimize the limitations of tPA treatment and possibly increase the therapeutic window for ischemic stroke treatment.
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spelling pubmed-61879402018-11-16 Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator Knecht, Talia Borlongan, Cesar dela Peña, Ike Brain Circ Review Article Tissue plasminogen activator (tPA) thrombolysis continues to be the gold standard therapy for ischemic stroke. Due to the time-limited treatment window, within 4.5 h of stroke onset, and a variety of potentially deadly complications related to delayed administration, particularly hemorrhagic transformation (HT), clinical use of tPA is limited. Combination therapies with other interventions, drug or nondrug, have been hypothesized as a logical approach to enhancing tPA effectiveness. Here, we discuss various potential pharmacological and nondrug treatments to minimize adverse effects, primarily HT, associated with delayed tPA administration. Pharmacological interventions include many that support the integrity of the blood–brain barrier (i.e., atorvastatin, batimastat, candesartan, cilostazol, fasudil, and minocycline), promote vascularization and preserve cerebrovasculature (i.e., coumarin derivative IMM-H004 and granulocyte-colony stimulating factor), employing other mechanisms of action (i.e., oxygen transporters and ascorbic acid). Nondrug treatments are comprised of stem cell transplantation and gas therapies with multi-faceted approaches. Combination therapy with tPA and the aforementioned treatments demonstrated promise for mitigating the adverse complications associated with delayed tPA treatment and rescuing stroke-induced behavioral deficits. Therefore, the conjunctive therapy method is a novel therapeutic approach that can attempt to minimize the limitations of tPA treatment and possibly increase the therapeutic window for ischemic stroke treatment. Medknow Publications & Media Pvt Ltd 2018 2018-10-09 /pmc/articles/PMC6187940/ /pubmed/30450415 http://dx.doi.org/10.4103/bc.bc_21_18 Text en Copyright: © 2018 Brain Circulation http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Review Article
Knecht, Talia
Borlongan, Cesar
dela Peña, Ike
Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title_full Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title_fullStr Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title_full_unstemmed Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title_short Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator
title_sort combination therapy for ischemic stroke: novel approaches to lengthen therapeutic window of tissue plasminogen activator
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187940/
https://www.ncbi.nlm.nih.gov/pubmed/30450415
http://dx.doi.org/10.4103/bc.bc_21_18
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