TY - JOUR
T1 - The Evolving Concept of the Blood Brain Barrier (BBB)
T2 - From a Single Static Barrier to a Heterogeneous and Dynamic Relay Center
AU - Villabona-Rueda, Andres
AU - Erice, Clara
AU - Pardo, Carlos A.
AU - Stins, Monique F.
N1 - Funding Information:
We would like to thank Hector Fabian Plata Santos for his input and help as a graphical designer in producing the artwork for the Graphical Abstract and Figure 1. Funding. This work was supported by the NIH RO1 HL 130649, the Johns Hopkins Malaria Research Institute, and Bloomberg Philanthropies to MS. CP was supported by the Johns Hopkins Project Restore and the Bart Mclean Fund for Neuroimmunology Research.
Publisher Copyright:
© Copyright © 2019 Villabona-Rueda, Erice, Pardo and Stins.
PY - 2019/9/20
Y1 - 2019/9/20
N2 - The blood–brain barrier (BBB) helps maintain a tightly regulated microenvironment for optimal central nervous system (CNS) homeostasis and facilitates communications with the peripheral circulation. The brain endothelial cells, lining the brain’s vasculature, maintain close interactions with surrounding brain cells, e.g., astrocytes, pericytes and perivascular macrophages. This function facilitates critical intercellular crosstalk, giving rise to the concept of the neurovascular unit (NVU). The steady and appropriate communication between all components of the NVU is essential for normal CNS homeostasis and function, and dysregulation of one of its constituents can result in disease. Among the different brain regions, and along the vascular tree, the cellular composition of the NVU varies. Therefore, differential cues from the immediate vascular environment can affect BBB phenotype. To support the fluctuating metabolic and functional needs of the underlying neuropil, a specialized vascular heterogeneity is required. This is achieved by variances in barrier function, expression of transporters, receptors, and adhesion molecules. This mini-review will take you on a journey through evolving concepts surrounding the BBB, the NVU and beyond. Exploring classical experiments leading to new approaches will allow us to understand that the BBB is not merely a static separation between the brain and periphery but a closely regulated and interactive entity. We will discuss shifting paradigms, and ultimately aim to address the importance of BBB endothelial heterogeneity with regard to the function of the BBB within the NVU, and touch on its implications for different neuropathologies.
AB - The blood–brain barrier (BBB) helps maintain a tightly regulated microenvironment for optimal central nervous system (CNS) homeostasis and facilitates communications with the peripheral circulation. The brain endothelial cells, lining the brain’s vasculature, maintain close interactions with surrounding brain cells, e.g., astrocytes, pericytes and perivascular macrophages. This function facilitates critical intercellular crosstalk, giving rise to the concept of the neurovascular unit (NVU). The steady and appropriate communication between all components of the NVU is essential for normal CNS homeostasis and function, and dysregulation of one of its constituents can result in disease. Among the different brain regions, and along the vascular tree, the cellular composition of the NVU varies. Therefore, differential cues from the immediate vascular environment can affect BBB phenotype. To support the fluctuating metabolic and functional needs of the underlying neuropil, a specialized vascular heterogeneity is required. This is achieved by variances in barrier function, expression of transporters, receptors, and adhesion molecules. This mini-review will take you on a journey through evolving concepts surrounding the BBB, the NVU and beyond. Exploring classical experiments leading to new approaches will allow us to understand that the BBB is not merely a static separation between the brain and periphery but a closely regulated and interactive entity. We will discuss shifting paradigms, and ultimately aim to address the importance of BBB endothelial heterogeneity with regard to the function of the BBB within the NVU, and touch on its implications for different neuropathologies.
KW - blood–brain barrier
KW - brain cellular heterogeneity
KW - cerebral endothelial cells
KW - neurovascular unit
KW - vascular heterogeneity
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U2 - 10.3389/fncel.2019.00405
DO - 10.3389/fncel.2019.00405
M3 - Review article
C2 - 31616251
AN - SCOPUS:85072960496
SN - 1662-5102
VL - 13
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
M1 - 405
ER -