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Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection.

ABSTRACT: Intravenous recombinant tissue-type plasminogen activator (r-tPA, alteplase) remains the recommended therapy for acute ischemic stroke. However, several factors are limiting its practical use. It makes it urgent for us to search more efficient strategies that can save the ischemic neurons, and safely extend the time window, while in the mean time reducing the detrimental effects for stroke thrombolysis. Hyperbaric oxygen therapy (HBOT) is considered to be potentially neuroprotective. Co-administration of r-tPA and HBOT has already been proved to be effective, safe and feasible in myocardial infarction. In this article, we would like to review whether HBOT has any beneficial effects on r-tPA thrombolysis. If there is, what is the underlying possible mechanisms and how to optimize for maximal effects?

SUBMITTER: Yang ZS

PROVIDER: S-EPMC5402349 | biostudies-literature | 2017 Jan-Mar

REPOSITORIES: biostudies-literature

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Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection.

Yang Ze-Song ZS Mu Jun J

Medical gas research 20170101 1

Intravenous recombinant tissue-type plasminogen activator (r-tPA, alteplase) remains the recommended therapy for acute ischemic stroke. However, several factors are limiting its practical use. It makes it urgent for us to search more efficient strategies that can save the ischemic neurons, and safely extend the time window, while in the mean time reducing the detrimental effects for stroke thrombolysis. Hyperbaric oxygen therapy (HBOT) is considered to be potentially neuroprotective. Co-administ ...[more]

PMID: 28480034

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Project description:Background and Purpose- Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods- Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results- Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions- The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

Dataset Information

Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection.

Publications

Co-administration of tissue plasminogen activator and hyperbaric oxygen in ischemic stroke: a continued promise for neuroprotection.

Similar Datasets

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