Tes and reduce the time to recanalization. Testing any thrombolytic th…

Tes 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 bmjopen-2016-011824 thromboembolic stroke PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/14960617 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 n-Phenylpiperazine-1-carboxamide 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. Keywords: Embolic Stroke, Microbubbles, Platelet Rich Clot, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24083752 Rat, Thrombolysis, Ultrasound, SonothrombolysisBackground Currently, the only approved thrombolytic treatment for acute ischemic stroke is recombinant tissue plasminogen activator (tPA) delivered intravenously within 4.5 hours of stroke onset [1]. However, less than 10 of all ischemic stroke patients are eligible for therapy [2] and tPA achieves successful recanalization in less than half of those treated [3]. Achieving higher recanalization rates* Correspondence: Max.Nedelmann@neuro.med.uni-giessen.de; neil.spratt@newcastle.edu.au 3 Department of Neurology, Justus-Liebig-University, Giessen, Germany 1 School of Biomedical Sciences Pharmacy, University of Newcastle, and Hunter Medical Research Institute, Newcastle, Australia Full list of author information is available at the end of the articlein a timely manner is a key goal to developing better stroke thrombolytic therapy. Use of ultrasound to enhance recanalization with tPA is a promising approach. The first clinical report of stroke sonothrombolysis indicated increased rates of recanalization in patients receiving continuous transcranial Doppler ultrasound (TCD) monitoring during tPA therapy [4]. Several small clinical 4,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolane trials with perflutren-lipid and galactosebased microbubbles as enhancers of sonothrombolysis suggest that microbubbles may produce further improvements in the rates of recanalization [5-8]. Despite the promise of this therapy, more than half of patients treated do not recanalize [9] and concerns have been raised regarding its?2015 Tomkins et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is p.