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Experimental & Translational Stroke Medicine
Published in: Experimental & Translational Stroke Medicine 1/2015

Open Access 01-12-2015 | Research

Platelet rich clots are resistant to lysis by thrombolytic therapy in a rat model of embolic stroke

Authors: Amelia J Tomkins, Nadine Schleicher, Lucy Murtha, Manfred Kaps, Christopher R Levi, Max Nedelmann, Neil J Spratt

Published in: Experimental & Translational Stroke Medicine | Issue 1/2015

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Abstract

Background

Early recanalization of occluded vessels in stroke is closely associated with improved clinical outcome. Microbubble-enhanced sonothrombolysis is a promising therapy to improve recanalization rates and reduce the time to recanalization. Testing any thrombolytic therapy requires a model of thromboembolic stroke, but to date these models have been highly variable with regards to clot stability. Here, we developed a model of thromboembolic stroke in rats with site-specific delivery of platelet-rich clots (PRC) to the main stem of the middle cerebral artery (MCA). This model was used in a subsequent study to test microbubble-enhanced sonothrombolysis.

Methods

In Study 1 we investigated spontaneous recanalization rates of PRC in vivo over 4 hours and measured infarct volumes at 24 hours. In Study 2 we investigated tPA-mediated thrombolysis and microbubble-enhanced sonothrombolysis in this model.

Results

Study 1 demonstrated stable occlusion out to 4 hours in 5 of 7 rats. Two rats spontaneously recanalized at 40 and 70 minutes post-embolism. Infarct volumes were not significantly different in recanalized rats, 43.93 ± 15.44% of the ischemic hemisphere, compared to 48.93 ± 3.9% in non-recanalized animals (p = 0.7). In Study 2, recanalization was not observed in any of the groups post-treatment.

Conclusions

Site specific delivery of platelet rich clots to the MCA origin resulted in high rates of MCA occlusion, low rates of spontaneous clot lysis and large infarction. These platelet rich clots were highly resistant to tPA with or without microbubble-enhanced sonothrombolysis. This resistance of platelet rich clots to enhanced thrombolysis may explain recanalization failures clinically and should be an impetus to better clot-type identification and alternative recanalization methods.
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Metadata
Title
Platelet rich clots are resistant to lysis by thrombolytic therapy in a rat model of embolic stroke
Authors
Amelia J Tomkins
Nadine Schleicher
Lucy Murtha
Manfred Kaps
Christopher R Levi
Max Nedelmann
Neil J Spratt
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Experimental & Translational Stroke Medicine / Issue 1/2015
Electronic ISSN: 2040-7378
DOI
https://doi.org/10.1186/s13231-014-0014-y