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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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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. |
format | Online Article Text |
id | pubmed-6187940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
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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