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A schematic overview of the blood-brain barrier
Modeling the blood-brain barrier
Because the brain is such a delicate organ, and because any substance that enters the brain can have a profound effect on behavior, memory or motor function, the exchange of substances between the blood and the brain is very tightly regulated. The central players in this regulation are the brain capillary endothelial cells. These cells form the barrier between the blood and the brain tissue. As such, they regulate transport into and out of the brain. The brain capillary endothelial cells are fundamentally different from endothelial cells that form the lining of all other blood vessels in the body. The brain capillary endothelial cells are not ‘leaky’ - all transport over the endothelium is specific.
Being able to predict which substances can cross the blood-brain barrier and which substances will not enter the brain is important in many fields of research and technology. For example, if tiny nanoparticles can cross the blood-brain barrier, this would greatly increase their toxicity. Alternatively, being able to predict which drugs will cross the blood-brain barrier would be of great help during drug development. So, a model for the blood-brain barrier is needed that is as realistic as possible, but which still can be used for quick screening of substances to determine whether they will enter the brain.
Figure 1: A schematic overview of the blood-brain barrier. Brain capillary endothelial cells are in direct contact with brain astrocytes and form a tight barrier between the blood and the brain. All transport of molecules from the blood to the brain and vice versa is regulated by these endothelial cells. Based on an image by Armin Kübelbeck.
A realistic model of the blood-brain barrier needs to meet three conditions. First of all, using actual brain capillary endothelial cells is better than using cell lines or cells of different origin. Second of all, culturing under dynamic conditions, thereby exposing the endothelial cell layer to mechanical shear stress, improves the quality of the barrier. And thirdly, the endothelial cells should be co-cultured with astrocytes from the brain, or at least in medium that is preconditioned by these cells.
By using a microfluidic approach, we are developing a model for the blood-brain barrier that meets all these three conditions and that can be used for testing dozens of substances in one assay.
INTERESTED?
If you are interested in this project and for instance would like to work on it for your graduation work or practical term, please contact Floor Wolbers or Andries van der Meer.
Dr. Floor Wolbers, Carré 2405, f.wolbers@utwente.nl, +31 (0)53 489 3944
Dr. Andries van der Meer, Carré 2441, a.d.vandermeer@utwente.nl, +31 (0)53 489 4851
