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Microbubble-mediated sonothrombolysis with BR38 of a venous full blood thrombus in a rat embolic stroke model

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Wietelmann,  Astrid
Small Animal Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Zitation

Braun, T., Suenner, L., Hachenberger, M., Mueller, C., Wietelmann, A., Juenemann, M., et al. (2021). Microbubble-mediated sonothrombolysis with BR38 of a venous full blood thrombus in a rat embolic stroke model. ANNALS OF TRANSLATIONAL MEDICINE, 9(13): 1061. doi:10.21037/atm-21-75.


Zitierlink: https://hdl.handle.net/21.11116/0000-0009-431C-D
Zusammenfassung
Background: Early recanalization of an occluded vessel is associated with a better clinical outcome in acute ischemic stroke. Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only available in a minority of patients and often fails to reopen the occluded vessel. Mechanical recanalization is more effective in this matter but only available for selected patients when a thrombectomy centre can be reached. Therefore, sonothrombolysis might represent an alternative or complementary approach. Here, we tested microbubble-mediated sonothrombolysis (mmSTL) in a thromboembolic stroke model for middle cerebral artery occlusion (MCAO) in rats.
Methods: Sixty-seven male Wistar rats underwent MCAO using an autologous full blood thrombus and were randomly assigned to four groups receiving rt-PA, mmSTL, a combination of both, or a placebo. Diagnostic workup included neurological examination, assessment of infarct size, and presence of intracerebral haemorrhage by magnetic resonance imaging (MRI) and presence of microbleedings in histological staining.
Results: Neurological examination revealed no differences between the treatment groups. In all treatment groups, there was a reduction in infarct size 24 hours after MCAO as compared to the placebo (P=0.05), but there were no differences between the active treatment groups (P>0.05) (placebo 0.75 +/- 0.10 cm(3); mmSTL 0.43 +/- 0.07 cm(3); rt-PA 0.4 +/- 0.07 cm(3); mmSTL + rt-PA 0.27 +/- 0.08 cm(3)). Histological staining displayed intracerebral microbleedings in all animals. The frequency of gross bleeding detected by MRI did not differ between the groups (placebo 3; mmSTL 4; rt-PA 2; mmSTL + rt-PA 2; P>0.05) and was not associated with worse performance in clinical testing (P>0.05). There were no statistical differences in the mortality between the groups (P>0.05).
Conclusions: Our study showed the efficacy and safety of mmSTL with or without rt-PA in an embolic rat stroke model using a continuous full blood thrombus. Sonothrombolysis might be useful for patients who need to be transported to a thrombectomy centre or for those with distal vessel occlusion.