In animal models, hyperosmolar agents like mannitol transiently disrupt the blood-brain barrier (BBB). Does anyone know of similar methods for BBB disruption in in vitro models, particularly in transwell systems?
Any suggestions on protocols or alternative agents would be helpful!
Hello Umeshi Karunadasa
Use vasoactive peptides like bradykinin which can activate specific receptors on endothelial cells, causing them to relax and increase permeability.
Also, certain toxins like mycotoxins, dioxins, polycyclic aromatic hydrocarbons or heavy metals used at very low concentrations, can disrupt the BBB by directly interacting with tight junction proteins.
Some small molecules like claudin-specific peptides, certain types of antibodies targeting junctional adhesion molecules (JAMs), small molecule inhibitors of tight junction proteins like occludin, and molecules that disrupt the actin cytoskeleton which supports the tight junctions can directly target and disrupt tight junction proteins, leading to increased permeability.
Please note that you will have to carefully control the concentration and exposure time to achieve a transient disruption without causing cell damage. Also, the endothelial cell line chosen for in vitro model can affect the response to BBB disrupting agents.
Best,
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