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Review
. 2021 Apr;246(7):835-844.
doi: 10.1177/1535370220977195. Epub 2020 Dec 10.

The neurovascular extracellular matrix in health and disease

Aric F Logsdon  1   2 , Elizabeth M Rhea  1   2 , May Reed  1   2 , William A Banks  1   2 , Michelle A Erickson  1   2
Affiliations
Review

The neurovascular extracellular matrix in health and disease

Aric F Logsdon et al. Exp Biol Med (Maywood). 2021 Apr.

Abstract

The blood-brain barrier (BBB) is a vital interface that supports normal brain functions. Endothelial cells (ECs) are the main component of the BBB and are highly specialized to govern the transfer of substances into brain. The EC lumen is enmeshed with an extracellular matrix (ECM), known as the endothelial glycocalyx layer (EGL). The lumen-facing EGL is primarily comprised of proteoglycans (PGs) and glycosaminoglycans (GAGs), which function as the first line of defense for blood-to-brain transfer of substances. Circulating factors must first penetrate the EGL before interacting with the EC. The abundance and composition of the PG and GAGs can dictate EGL function, and determine which circulating substances communicate with the ECs. The EGL can interact with circulating factors through physio-chemical interactions with the EC. Some disease states reveal a "thinning" of the EGL that may increase EC interactions with components of the systemic circulation and alter BBB function. EGL changes may also contribute to the cognitive complications of systemic diseases, such as sepsis and diabetes. For decades, researchers have measured how genetic and environmental factors influence the peripheral EGL constituents; however, much less is known about the neurovascular EGL. In this mini-review, we introduce components of the EGL and innovative ways to measure their abundance and composition that may contribute to BBB dysfunction.

Keywords: Glycocalyx; blood–brain barrier; extracellular matrix; glycosaminoglycans; proteoglycans.

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Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Structure and function of the neurovascular glycocalyx. Prominent components of the luminal (blood-facing) side of the endothelial glycocalyx layer (EGL) include: proteoglycans (PGs; syndecan, glypican, and biglycan), and glycosaminoglycans (GAGs; chondroitin sulfate, heparan sulfate and hyaluronan). EGL functions are demonstrated including, physiochemical and mechanical interactions. Created with BioRender.com. (A color version of this figure is available in the online journal.)
Figure 2.
Figure 2.
Methods to assess the neurovascular glycocalyx. Technological advancements including: (a) two-photon microscopy (TPM), (b) stochastic optical reconstruction microscopy (STORM), (c) electron microscopy (EM), and (d) mass spectroscopy (MS) have enhanced our understanding of the endothelial glycocalyx layer (EGL). Each illustration represents the basic concept and model system for each technology. Created with BioRender.com. (A color version of this figure is available in the online journal.)
See this image and copyright information in PMC

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