Abstract
BackgroundEarly recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model.MethodsWe tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography.ResultsTotal vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1).ConclusionsMicrobubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory.
Highlights
Transcranial ultrasound combined with microbubbles augments thrombolysis in clinical studies and experimental animal models of acute intracranial arterial occlusion [1,2,3,4]
We tested BR38 and SonoVue1 microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery
This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory
Summary
Transcranial ultrasound combined with microbubbles augments thrombolysis in clinical studies and experimental animal models of acute intracranial arterial occlusion [1,2,3,4]. Microbubbles are ultrasound contrast agents used diagnostically and, when administered with rt-PA and ultrasound, have the potential to improve thrombi dissolution [5]. Microbubbles lower the energy requirements for producing sonothrombolysis thereby increasing the lytic activity of ultrasound [6]. Recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model
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