Abstract
The blood-brain barrier (BBB) is one of the most selective endothelial barriers. An understanding of its cellular, morphological, and biological properties in health and disease is necessary to develop therapeutics that can be transported from blood to brain. In vivo models have provided some insight into these features and transport mechanisms adopted at the brain, yet they have failed as a robust platform for the translation of results into clinical outcomes. In this article, we provide a general overview of major BBB features and describe various models that have been designed to replicate this barrier and neurological pathologies linked with the BBB. We propose several key parameters and design characteristics that can be employed to engineer physiologically relevant models of the blood-brain interface and highlight the need for a consensus in the measurement of fundamental properties of this barrier.
Highlights
Barrier properties are acquired via the canonical Wingless–Int1 (Wnt)/β-catenin signaling pathway, which is responsible for the upregulation of tight junctions (TJs) in brain endothelial cells and the induction of barrier properties in the invading vasculature [7]
Barriergenesis enables endothelial cells to acquire a full blood–brain barrier (BBB) phenotype by increasing their expression of glucose transporter 1 (GLUT-1), claudins, and P-glycoprotein following the sustained secretion of different factors by cells of the central nervous system (CNS), such as platelet-derived growth factor B (PDGF-B) from pericytes [8] and retinoic acid from astrocytes [9]
Pericytes fully wrap around the brain capillaries formed by endothelial cells, and astrocytes physically connect their endfeet to the abluminal side of the endothelium covering a small area of the vessel
Summary
Several morphological features of the BBB inform its functional properties, governing the controlled transport of nutrients, molecules, and therapeutics from blood to brain (Figure 1). Comparison of barrier permeability to solutes and TEER in terms of the type of endothelial cells employed (nonbrain, primary, immortalized, and iPSC-derived) and the type of BBB model (cell culture insert, 2D chip, 3D vessel-like, 3D self-assembled). In vivo and in vitro models for which the area of the endothelium is well defined Both solute permeability and TEER measure transport of different types of solutes across the barrier, they are negatively correlated. After its first implementation in frog mesentery, the TEER technique was used in rat BBB capillaries, yielding values close to 6,000 /cm, significantly higher than those found in in vitro BBB models [48] These discrepancies partly reflect the relatively poor barrier function of in vitro BBB monolayer systems, where ionic transport cannot be fully recapitulated. TEER measurements should be interpreted with caution, since several parameters can significantly affect the results
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
