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Review
. 2020 Jul 16;17(1):44.
doi: 10.1186/s12987-020-00202-7.

Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms

Anuska V Andjelkovic  1 , Svetlana M Stamatovic  2 , Chelsea M Phillips  3 , Gabriela Martinez-Revollar  2 , Richard F Keep  4   5
Affiliations
Review

Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms

Anuska V Andjelkovic et al. Fluids Barriers CNS. .

Abstract

The complexity of the blood-brain barrier (BBB) and neurovascular unit (NVU) was and still is a challenge to bridge. A highly selective, restrictive and dynamic barrier, formed at the interface of blood and brain, the BBB is a "gatekeeper" and guardian of brain homeostasis and it also acts as a "sensor" of pathological events in blood and brain. The majority of brain and cerebrovascular pathologies are associated with BBB dysfunction, where changes at the BBB can lead to or support disease development. Thus, an ultimate goal of BBB research is to develop competent and highly translational models to understand mechanisms of BBB/NVU pathology and enable discovery and development of therapeutic strategies to improve vascular health and for the efficient delivery of drugs. This review article focuses on the progress being made to model BBB injury in cerebrovascular diseases in vitro.

Keywords: Blood–brain barrier; Brain vascular malformation; In vitro models; Neurovascular units; Stroke; Vascular dementia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. RFK is a co-editor in chief of Fluids Barriers CNS.

Figures

Fig. 1
Fig. 1
Flowchart summarizing clinical classification of cerebrovascular disease
Fig. 2
Fig. 2
Blood brain barrier (BBB) and neurovascular unit. a Schematic representation of cellular structure of BBB/NVU. b Brain endothelial cells have a wide range of transporters and carriers that build BBB influx (blood–brain) and BBB efflux (brain-blood) systems. c The BBB-endowed brain endothelial cells are characterized by a junctional complex that completely occludes the paracellular space and restricts paracellular movement from blood to brain. The junctional complex is composed from tight junctions (TJ), adherens junctions (AdJ) and gap junctions (GJ). These structures are generated by a complex network of protein–protein interactions between transmembrane proteins (e.g. claudin-5, occludin, junctional adhesion molecules [JAM], Ve-cadherin and Cx43) with scaffolding proteins (i.e. ZO-1) and the actin cytoskeletons
Fig. 3
Fig. 3
Current models of blood–brain barrier (BBB)/neurovascular unit (NVU) in vitro. The flowchart summarizes the advantages and disadvantages of the current 2-D and 3-D models of BBB/NVU. BEC, brain endothelial cell; iPSC, induced pluripotent stem cell, DIV-BBB, dynamic in vitro BBB model; μBBB, microfluidic-based BBB; SyM-BBB, synthetic microvascular model of BBB
See this image and copyright information in PMC

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