Microbubbles improve sonothrombolysis in vitro and decrease hemorrhage in vivo in a rabbit stroke model.

Area of Science:

• Biomedical Engineering
• Neurology
• Pharmacology

Background:

• Tissue plasminogen activator (tPA) is the standard thrombolytic therapy for acute ischemic stroke.
• Intracerebral hemorrhage (ICH) is a significant and dangerous complication of tPA treatment.
• Investigating novel methods to enhance tPA efficacy and mitigate hemorrhage risk is crucial.

Purpose of the Study:

• To evaluate the combined efficacy of ultrasound (US) and microbubbles (MB) with tPA in thrombolysis.
• To determine if this combination can reduce the required tPA dosage.
• To assess the impact of US-MB-tPA therapy on reducing intracerebral hemorrhage (ICH).

Main Methods:

• In vitro experiments exposed blood clots to tPA with or without US and MBs (Definity or adMB).
• In vivo studies in rabbits involved inducing carotid artery clots and treating with intravenous tPA and transcutaneous US, with or without Definity MBs.
• Thrombolysis was quantified by clot mass loss; infarct volume and ICH incidence were assessed via histology.

Main Results:

• Microbubbles significantly enhanced US-induced clot dissolution, with or without tPA, in vitro.
• The combination therapy allowed for a 5-fold reduction in tPA dose with maintained efficacy.
• In vivo, US-MB-tPA significantly reduced infarct volume and lowered ICH incidence compared to controls and tPA alone.

Conclusions:

• Combining tPA with ultrasound and microbubbles is an effective strategy for clot lysis in acute stroke models.
• This approach significantly reduces the necessary tPA dose, leading to decreased infarct volumes and hemorrhage rates.
• The findings suggest that US-MB-tPA therapy holds promise for improving stroke treatment outcomes by minimizing ICH risk.