Stem Cell-Based Human Blood–Brain Barrier Models for Drug Discovery and Delivery

International audienceThe development of novel neuropharmaceuticals requires the evaluation of blood-brain barrier (BBB) permeability and toxicity. Recent studies have highlighted differences in the BBB among different species, with the most important differences involving the expression of P-glycoprotein (P-gp), multidrug resistance-associated proteins, transporters, and claudins. In addition, functional studies have shown that brain pharmacokinetics of P-glycoprotein substrates are different in humans and rodents. Therefore, human BBB models may be an important platform for initial drug screening before in vivo studies. This strategy might help to reduce costs in drug development and failures in clinical studies. We review the differences in the BBB among species, recent advances in the generation of human BBB models, and their applications in drug discovery and delivery

Blood–Brain Barrier In Vitro Models and Their Applications in Toxicology

International audienceLocated at the level of brain capillaries, the blood–brain barrier (BBB) is a crucial component of the neurovascular unit, since its highly regulated properties are needed to maintain optimal conditions for proper neuronal and glial functions. By modelling the BBB it is possible to make predictions about whether a compound’s interaction with the BBB is likely to compromise its functionality. A dysfunctional BBB may either affect brain entry of an agent or indirectly generate unwanted effects on neurons and glial cells by disturbing the brain homeostasis.Since the BBB controls the exchanges between the blood and brain compartments modelling the BBB in vitro can also help to investigate the ability of compounds to cross the BBB. In this chapter, the plethora of in vitro BBB models that exist today is discussed and several methods needed to set up and use of these in vitro models in the framework of in vitro toxicity study is detailed