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Review
. 2021 Nov 19:14:752781.
doi: 10.3389/fnmol.2021.752781. eCollection 2021.

Tight Junctions of the Neurovascular Unit

Natalie Hudson  1 , Matthew Campbell  1
Affiliations
Review

Tight Junctions of the Neurovascular Unit

Natalie Hudson et al. Front Mol Neurosci. .

Abstract

The homeostatic balance of the brain and retina is maintained by the presence of the blood-brain and inner blood-retinal barrier (BBB/iBRB, respectively) which are highly specialized barriers. Endothelial cells forming the lining of these blood vessels are interconnected by the presence of tight junctions which form the BBB and iBRB. These tight junctions, formed of numerous interacting proteins, enable the entry of molecules into neural tissues while restricting the entry of harmful material such as anaphylatoxins, bacteria and viruses. If the tight junction complex becomes dysregulated due to changes in expression levels of one or more of the components, this can have detrimental effects leading to brain and retinal pathology.

Keywords: blood brain barrier; endothelial cells; inner blood-retinal barrier; neurovasculature; tight junction.

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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.

Figures

FIGURE 1
FIGURE 1
Cellular and tight junction (TJ) protein composition of the blood- brain barrier (BBB) and inner blood-retinal barrier (iBRB). (A) Schematic of the blood brain barrier (BBB) neurovascular unit (NVU). A single endothelial cell (EC) forms the lumen of the blood vessels surrounded by a pericyte (P) and the basement membrane (BM) containing laminins, nidogens, collagen IV and heparin sulfate proteoglycans. Astrocytes (AS) end-feet ensheath the cell complex with neurone (N) and microglia (M) present in the microenvironment. (B) The iBRB is similar in composition to the BBB (as seen in A) although pericytes (P) are at a ratio of 1:1 with endothelial cells (EC) and Muller cell (MC) processes wrap around the blood vessels along with the astrocytes (AS). The iBRB is found in the retina from the ganglion cell layer (GCL) to the outer nuclear layer (ONL). (C) Schematic of tight junction proteins expressed that join the same endothelial cell or adjacent endothelial cells to one another. Claudin-5 is expressed most abundantly with contribution from claudin 1 and 12 (other family members shown to be expressed in other NVU cells). The TAMPs (occludin, tricelllin) and LSR along with JAM family members (A–C and ESAM) constitute the additional transmembrane proteins. Zonula occludens (ZO) 1 and 2 are expressed cytoplasmic which can form a structural link to the actin cytoskeleton and associate with actin binding proteins.
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