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Microbubble-mediated sonothrombolysis: an in vitro mechanistic study

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Defense Thèse de doctorat : Univ. Genève, 2014 - Sc. 4694 - 2014/06/18
Abstract In the context of ischemic stroke treatment, sonothrombolysis appears as a promising approach. Initially based on the use of ultrasound only, sonothrombolysis has taken on a new dimension with the introduction of microbubbles to reinforce the ultrasound action. Nonetheless the exact mechanisms involved remain partially unknown. This thesis evaluates a phospholipid microbubble formulation as sonothrombolysis enhancer and intends to explore in vitro the mechanisms of the process. Microbubbles, when combined with ultrasound, were shown to largely reinforce the thrombolysis mediated by recombinant tissue plasminogen activator (rtPA); and in appropriate conditions were able to perform effective clot lysis with considerably lowered rtPA doses. Quantification of fibrin degradation products further showed that the presence of a fibrinolytic drug was necessary to induce any fibrin dissolution. Finally, microbubbles and ultrasound were shown to act in synergy with rtPA, and to promote fibrin degradation thanks to stable and inertial cavitation phenomena.
Keywords SonothrombolysisIschemic strokeUltrasoundMicrobubblesRecombinant tissue plasminogen activatorFibrinCavitation
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URN: urn:nbn:ch:unige-418986
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Thesis (6.7 MB) - public document Free access
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Research group Technologie pharmaceutique
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PETIT, Bénédicte. Microbubble-mediated sonothrombolysis: an in vitro mechanistic study. Université de Genève. Thèse, 2014. https://archive-ouverte.unige.ch/unige:41898

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Deposited on : 2014-11-17

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