Saturday, October 22, 2022

Blood brain barrier proteomics investigates the mechanisms of propofol!


It seems like basically every time someone starts really talking about how a drug works at a cellular or molecular level, you end up getting to a lot of question marks. When you start talking about drugs in the brain it sometimes feels like...

One of the important concepts that gets tossed around all the time is whether something crosses the blood brain barrier (BBB). What is that, besides the thing the words indicate? Please see gif above. Could you study how it works with proteomics? Again, please reference the 13th regeneration of the Doctor above. 

According to this nice new review it is a complex system of different cells working together, and you can there are multiple ways to study it which all have their own relative advantages and disadvantages (stole the summary table, click to expand.). 

One way to study it is to build your own blood brain barrier model in your own incubator, then you do crazy stuff like dose cells with different drugs, which is what this group did with propofol! 

I only thing that I associate with the drug propofol is the untimely demise of some pop music legends. And this synthetic blood brain barrier (BBB) model suggests that this compound is really bad for a number of different reasons. Adding propofol makes their BBB model more permeable and when they pull the cells for proteomics, these cells have some weird effects.

(Data was acquired with an Exploris 480 and data was processed with Proteome Discoverer. Results are on PRIDE as PXD033856) 

One thing they observe is a loss in H2AX after treatment. And that is one of the central proteins involved in observing and reparing DNA damage. After their proteomics they back it up with a western blot, which made me throw up in my mouth a little, but they probably had to do it to get a senior scientist to sign off on the paper and I've been told that I eat really weird stuff. There is other cool stuff in here, but I can't spend all morning reading about BBBs and throwing up because someone "validated" some HRAM data with rabbit blood and horseradishes. 

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