Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for...

Area of Science:

• Neuroscience
• Biomedical Engineering
• Pharmacology

Background:

• Cerebral ischemia reperfusion (IR) injury involves inflammatory responses.
• Activated microglia contribute to secondary injury in the later stages of cerebral ischemia.
• Targeting activated microglia is crucial for mitigating neuroinflammation post-IR.

Purpose of the Study:

• To investigate if phosphatidylserine (PS)-modified microbubbles (PS-MBs) with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood-brain barrier (BBB).
• To determine if PS-MBs can target activated microglia in the inflammatory areas during the later stages of IR.
• To evaluate the therapeutic potential of this approach for neuroinflammation.

Main Methods:

• Establishment of a rat model of cerebral ischemia reperfusion (IR).
• Observation of activated microglia/macrophage (M/M) and BBB permeability at various time points post-IR (1, 7, 14, 21 days).
• In vitro and in vivo assessment of PS-MBs uptake by activated M/M.

Main Results:

• Activated M/M were observed throughout the experimental period.
• Evans blue extravasation, indicating BBB permeability, gradually decreased from day 1 to day 21.
• PS-MBs showed approximately twofold greater uptake by activated M/M compared to controls, both in vitro and in vivo.

Conclusions:

• PS-MBs combined with ultrasound (US) exposure can safely open the BBB.
• The resulting PS nanoparticles (PS-NPs) effectively target activated M/M in neuroinflammatory conditions.
• This strategy offers a promising approach for treating late-stage neuroinflammation following cerebral IR injury.