The endothelial blood–brain barrier (BBB) protects central nervous system (CNS) neurons from the changeable milieu of the bloodstream by strictly controlling the movement of molecules and immune cells between the blood and the CNS. Immune cell migration across the vascular wall is a multistep process regulated by the sequential interaction of different signaling and adhesion molecules on the endothelium and the immune cells. Accounting for its unique barrier properties and trafficking molecule expression profile, particular adaptions in immune cell migration across the BBB have been observed. Thus, in vitro models of the BBB are desirable to explore the precise cellular and molecular mechanisms involved in immune cell trafficking across the BBB. The challenge to overcome is that barrier properties of brain microvascular endothelial cells are not intrinsic and readily lost in culture. With a focus on human in vitro BBB models, we here discuss the suitability of available in vitro models for the BBB for exploring the specific mechanisms involved in immune cell trafficking across the BBB.
