Extracellular vesicles through the blood-brain barrier: a review

Area of Science:

• Neuroscience
• Cell Biology
• Biotechnology

Background:

• Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, incapable of replication.
• The bidirectional transport of EVs across the Blood-Brain Barrier (BBB) between the bloodstream and brain parenchyma is poorly understood.
• Current in vitro models inadequately represent the BBB's complex cellular structure and regional variations.

Purpose of the Study:

• To review and analyze in vitro and in vivo methodologies for evaluating EV transcytosis across the BBB.
• To elucidate the mechanisms by which EVs traverse the BBB.
• To discuss future methodological advancements for studying EV-BBB interactions.

Main Methods:

• Review of existing literature on in vitro models (transwell, organ-on-a-chip) and in vivo studies (zebrafish).
• Critical assessment of techniques used to visualize and quantify EV motion across the BBB.
• Identification of inconsistencies in current methodologies.

Main Results:

• Existing in vitro models fail to capture the BBB's full cellular complexity.
• Direct in vivo visualization of EV transcytosis across the mammalian BBB is lacking; zebrafish studies provide limited evidence.
• Literature on EV-BBB transport mechanisms is scarce and methodologies are inconsistent.

Conclusions:

• Current methods for studying EV transport across the BBB are insufficient.
• Further research is needed to develop and validate advanced techniques for in vivo visualization and mechanistic studies.
• Understanding EV-BBB interactions is crucial for developing EVs as drug delivery vehicles for neurological disorders.