Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in The Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome and Type 2 Diabetes Mellitus

Version 1 : Received: 18 August 2023 / Approved: 21 August 2023 / Online: 21 August 2023 (08:06:57 CEST)

A peer-reviewed article of this Preprint also exists.

Hayden, M.R. The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Life 2023, 13, 1955. Hayden, M.R. The Brain Endothelial Cell Glycocalyx Plays a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus. Life 2023, 13, 1955.

Abstract

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

Keywords

Blood-brain barriier; Blood-cerebrospinal fluid barrier; Endothelial glycocalyx; Enlarged perivascular spaces; Metabolic Syndrome; Neuroinflammation; Obesity; Perivascular spaces; T2DM

Subject

Biology and Life Sciences, Anatomy and Physiology

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