Human glycocalyx shedding: Systematic review and critical appraisal

Hahn, Robert G.; Patel, Vasu; Dull, Randal O.

doi:10.1111/aas.13797

Cited by 47 publications

(62 citation statements)

References 248 publications

(103 reference statements)

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“…The glycocalyx is the least-studied component of the BBB, and further work is required, particularly with regard to developing methods to measure its integrity in vivo, such as sidestream dark-field imaging [ 76 ]. There are some correlations between systemic glycocalyx thickness and the plasma concentrations of glycocalyx degradation markers [ 77 ]. Comparative studies of the brain and systemic glycocalyx are needed to identify specific molecular components of the BBB glycocalyx, the plasma concentrations of which may serve as markers of BBB integrity.…”

Section: Bbb Molecular and Cellular Anatomymentioning

confidence: 99%

The blood–brain barrier in systemic infection and inflammation

2021

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The vascular blood–brain barrier is a highly regulated interface between the blood and brain. Its primary function is to protect central neurons while signaling the presence of systemic inflammation and infection to the brain to enable a protective sickness behavior response. With increasing degrees and duration of systemic inflammation, the vascular blood–brain barrier becomes more permeable to solutes, undergoes an increase in lymphocyte trafficking, and is infiltrated by innate immune cells; endothelial cell damage may occasionally occur. Perturbation of neuronal function results in the clinical features of encephalopathy. Here, the molecular and cellular anatomy of the vascular blood–brain barrier is reviewed, first in a healthy context and second in a systemic inflammatory context. Distinct from the molecular and cellular mediators of the blood–brain barrier’s response to inflammation, several moderators influence the direction and magnitude at genetic, system, cellular and molecular levels. These include sex, genetic background, age, pre-existing brain pathology, systemic comorbidity, and gut dysbiosis. Further progress is required to define and measure mediators and moderators of the blood–brain barrier’s response to systemic inflammation in order to explain the heterogeneity observed in animal and human studies.

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Section: Bbb Molecular and Cellular Anatomymentioning

confidence: 99%

The blood–brain barrier in systemic infection and inflammation

2021

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“…By contrast, arterio‐venous shunting in the legs increases during spinal anesthesia 17 and should reduce the endothelial surface available for filtration. Shedding of the endothelial glycocalyx layer might alter the capillary permeability, but the role of this process in the distribution of crystalloid fluid is unclear at present 18 …”

Section: Discussionmentioning

confidence: 99%

“…Shedding of the endothelial glycocalyx layer might alter the capillary permeability, but the role of this process in the distribution of crystalloid fluid is unclear at present. 18 The kinetic analysis operates on the assumption that the body is a single entity, which is only true for the arterial blood after the infusion has ended. Further analysis of this issue, which is given in Data S1, indicates that twice as much of the body volume was subject to vasodilatation than to vasoconstriction when the MAP was 60 mmHg, which seems to be reasonable.…”

Section: Limitationsmentioning

confidence: 99%

Model‐predicted capillary leakage in graded hypotension: Extended analysis of experimental spinal anesthesia

Hahn

Drobin

2021

Acta Anaesthesiol Scand

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Background Crystalloid fluid infused during the induction of spinal anesthesia is involved in a complex set of physiological responses, including vasodilatation, reactive vasoconstriction, and changes in mean arterial pressure (MAP). The present evaluation compares the modeled capillary leakage in anesthetized versus nonanesthetized body regions. Methods Ten female volunteers (mean age, 29 years) received 25 ml/kg of Ringer's acetate over 60 min during experimental spinal anesthesia. Blood hemoglobin was measured repeatedly in the radial artery (reference), arm (cubital) vein, and leg (femoral) vein for 240 min. Each pattern of data served as a dependent variable in volume kinetic analyses that used mixed models software and MAP as covariate. Results The capillary leakage of fluid from the plasma to the extravascular space peaked at 17 ml/min when MAP was 100 mmHg, and the two venous curves were virtually identical. At MAP 60 mmHg, the rate was reduced to 10‐12 ml/min when assessed in arterial blood and leg vein blood, but only 5 mmHg in blood collected from the arm vein. The distribution half‐life of infused fluid was then 40 min in the leg and 80 min in the arm. These results suggest that vasoconstriction in nonanesthetized body regions halves the capillary leakage that is observed in vasodilated, anesthetized body regions. Conclusion Graded hypotension during spinal anesthesia reduced the capillary filtration of fluid as determined by volume kinetic analysis. The effect was twice as great when venous blood was sampled from a nonanesthetized body region than from an anesthetized body region.

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“…In renal glomerular capillaries, the zone of exclusion for infused intralipid droplets was ~200 nm and was also significantly reduced by enzymes that cleave glycosaminoglycans ( 114 ) and by elution of ESL components with hypertonic NaCl ( 115 ). Evaluation of the EC glycocalyx/ESL thickness is now a commonly used technique in human clinical research ( 116 ) and has helped define changes in the height of the glycocalyx/ESL in disease.…”

Section: Physical Structure Of the Glomerular Ec Glycocalyx And Surface Layermentioning

confidence: 99%

“…The lattice-like arrangement of the EC coat furthermore suggests that it participates in size-selectivity of the GCW. It is already well-established that immune-activation of EC changes its glycocalyx, breaching the normal glycocalyx/ESL ( 116 ), allowing EC interactions with circulating cells and platelets and facilitating thrombosis ( 117 ). Under those conditions it is therefore expected that permselectivity is also reduced.…”

Section: Physical Structure Of the Glomerular Ec Glycocalyx And Surface Layermentioning

confidence: 99%

The Glomerular Endothelium Restricts Albumin Filtration

2021

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Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.

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Human glycocalyx shedding: Systematic review and critical appraisal

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 47 publications

References 248 publications

The blood–brain barrier in systemic infection and inflammation

The blood–brain barrier in systemic infection and inflammation

Model‐predicted capillary leakage in graded hypotension: Extended analysis of experimental spinal anesthesia

The Glomerular Endothelium Restricts Albumin Filtration

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