Abstract
The homeostasis of the central nervous system (CNS) is ensured by the endothelial, epithelial, mesothelial and glial brain barriers, which strictly control the passage of molecules, solutes and immune cells. While the endothelial blood-brain barrier (BBB) and the epithelial blood-cerebrospinal fluid barrier (BCSFB) have been extensively investigated, less is known about the epithelial and mesothelial arachnoid barrier and the glia limitans. Here, we summarize current knowledge of the cellular composition of the brain barriers with a specific focus on describing the molecular constituents of their junctional complexes. We propose that the brain barriers maintain CNS immune privilege by dividing the CNS into compartments that differ with regard to their role in immune surveillance of the CNS. We close by providing a brief overview on experimental tools allowing for reliable in vivo visualization of the brain barriers and their junctional complexes and thus the respective CNS compartments.
Highlights
The brain barriers established by the endothelial blood-brain barrier (BBB), the epithelial blood-cerebrospinal fluid barrier (BCSFB), the meningeal brain barriers and the blood spinal cord barrier are essential for maintaining central nervous system (CNS) homeostasis [1]
There are still a lot of unresolved questions concerning the precise molecular composition and interaction of Tight Junctions (TJs) and Adherens Junctions (AJs) of the brain barriers, which have hampered the development of therapeutic strategies targeting the brain barriers in neuroinflammatory disorders
Regarding the BBB, it has been recently confirmed by several reports that claudin-1 and claudin-3 are absent from BBB endothelial cells and claudin-5 is the only critical TJ claudin proven to date to contribute for the mouse BBB function [102]
Summary
The brain barriers established by the endothelial blood-brain barrier (BBB), the epithelial blood-cerebrospinal fluid barrier (BCSFB), the meningeal brain barriers and the blood spinal cord barrier are essential for maintaining central nervous system (CNS) homeostasis [1]. TTaakkeenn ttooggeetthheerr,, jjuunnccttiioonnaall ccoommpplleexxeess eessttaabblliisshheedd bbeettwweeeenn cceellllss ooff tthhee bbrraaiinn bbaarrrriieerrss mmiigghhtt nnoott oonnllyy ddiiffffeerrbbeetwtweeeennthtehedidffiefrfeenretnbtarbraierrrisebrsutbaultsoalwsoithwinithonine roensepercetsipveecbtiavreriebraarlroienrgatlhoenrgostthrealr-coasutrdaal-l caaxuisd. Sci. 2019, 20, 5372 the BBB via the paracellular route [18,19,20] They have very low pinocytosis rates when compared to the peripheral endothelium [21,22]. To ensure the passage of nutrients from the blood into the CNS and to remove potential toxic agents from the brain, the BBB endothelial cells express specific transporters and efflux pumps [25,26,27]. The barrier characteristics referred to above are present at the level of the endothelial cells forming the BBB in the post-capillary venules. The ChP vasculature is characterized by fenestrae allowing free access of blood components into the ChP stroma [37]
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