Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model

Area of Science:

• Biomedical Engineering
• Neuroscience
• Pharmacology

Background:

• Current stroke therapies, like tissue plasminogen activator (tPA), have limited efficacy due to narrow treatment windows.
• Delays in seeking medical attention often exclude patients from timely stroke treatment.
• Dodecafluoropentane emulsion (DDFPe) nanodroplets demonstrate potential as oxygen carriers and neuroprotective agents.

Purpose of the Study:

• To investigate if DDFPe can safely extend the therapeutic time window for tPA in a rabbit stroke model.
• To evaluate the combined efficacy of DDFPe and tPA in improving neurological outcomes and reducing infarct volume.

Main Methods:

• A rabbit model of ischemic stroke was induced by internal carotid artery occlusion.
• Animals received either tPA alone, DDFPe plus tPA, or no therapy.
• DDFPe was administered intravenously starting 1 hour post-stroke, with subsequent doses every 90 minutes for 6 doses.
• Standard tPA therapy was initiated 9 hours post-stroke in both treatment groups.
• Neurological Assessment Scores (NAS) and percent stroke volume (%SV) were measured at 24 hours.

Main Results:

• The DDFPe + tPA group showed significantly improved NAS (p = 0.0015) and reduced %SV (p = 0.0003) compared to controls and tPA alone.
• Neurological scores were significantly better in the DDFPe + tPA group versus tPA alone (p = 0.0052).
• Percent stroke volume was significantly reduced in the DDFPe + tPA group compared to tPA alone (p = 0.0018).

Conclusions:

• Dodecafluoropentane emulsion (DDFPe) significantly extends the therapeutic time window for tPA in treating ischemic stroke.
• Combined DDFPe and tPA therapy offers superior neuroprotection and functional recovery compared to tPA alone when initiated late after stroke onset.
• This approach holds promise for increasing the number of patients eligible for effective stroke treatment.