Blood-brain barrier on a chip.

The blood-brain barrier (BBB) plays a vital role in the maintenance of brain homeostasis. It strictly restricts the passage of molecules from the brain vasculature into the brain via its high transendothelial electrical resistance and low paracellular and transcellular permeability. Specialized brain endothelial cells, astrocytes, pericytes, neurons, and microglia contribute synergistically to the functional properties of the BBB. Because of its complexity and relative inaccessibility, BBB research is fraught with difficulties. Most studies rely on animal or cell culture models, which are not able to fully recapitulate the properties of the human BBB. The recent development of three-dimensional (3D) microfluidic models of the BBB could address this issue. This chapter aims to provide an overview of the recent advances in modeling the BBB on microdevices, and illustrate important considerations for the design of such models. In addition, protocols for the fabrication of a 3D BBB microfluidic chip and BBB assessment experiments, including immunocytochemistry for analyzing cell morphology and protein marker expression, permeability assay, and calcium imaging for studying neuronal function as a measure of BBB integrity, are presented here. It is envisioned that continued advancements in microtechnology can lead to the creation of realistic in vivo-like BBB-on-chip models.