Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Yoon, Jin-Hui; Shin, Paul; Joo, JongYoon; Kim, Gaon S; Oh, Wang‐Yuhl; Jeong, Yong Hoon

doi:10.1177/0271678x221076568

Cited by 18 publications

(21 citation statements)

References 86 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that the endothelial glycocalyx is degraded in diseases, leading to increased leukocyte adhesion ( Kumase et al, 2010 ; Schmidt et al, 2012 ; McDonald et al, 2016 ). Furthermore, the decreased extent of the cerebral endothelial glycocalyx is associated with increased capillary stalling ( Yoon et al, 2022 ). RNA-seq results also suggested that leukocyte-endothelial cell interaction could be enhanced in pericyte-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…Body temperature was maintained at 36.5–37.5°C with the use of a heating pad and a rectal feedback probe (Harvard Apparatus, 55-7020). Our procedures for OCTA data analysis have been described previously ( Yoon et al, 2022 ). Maximum intensity projection of 3D OCT angiograms was performed in a depth direction over 150–300 μm below the cortical surface.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, genes that are known to maintain the structure of the endothelial glycocalyx, such as Tek, Bgn, Dcn, Gpc3, B4galt3, Papss2, and Slc35b3, were significantly downregulated in the brain capillaries of pericyte-deficient mice (Figure 3B). In addition, a previous study reported that the extent of the cerebral endothelial glycocalyx is smaller in the stalled segments of the capillaries (Yoon et al, 2022). Therefore, we measured the extent of the cerebral endothelial glycocalyx in pericyte-deficient mice by using the region that best matched the capillary image plane (dotted square in Figure 3C).…”

Section: Pericyte Loss Decreases the Extent Of The Cerebral Endotheli...mentioning

confidence: 99%

“…Recently, it was shown that the extent of the cerebral endothelial glycocalyx was related to capillary stalling ( Yoon et al, 2022 ). The endothelial glycocalyx is a scaffolding network of proteoglycans, glycoproteins, glycosaminoglycans, and associated plasma proteins on the luminal side of the vascular endothelium ( Weinbaum et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pericyte Loss Leads to Capillary Stalling Through Increased Leukocyte-Endothelial Cell Interaction in the Brain

Choe

Yoon

Joo

et al. 2022

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

The neurovascular unit is a functional unit composed of neurons, glial cells, pericytes, and endothelial cells which sustain brain activity. While pericyte is a key component of the neurovascular unit, its role in cerebral blood flow regulation remains elusive. Recently, capillary stalling, which means the transient interruption of microcirculation in capillaries, has been shown to have an outsized impact on microcirculatory changes in several neurological diseases. In this study, we investigated capillary stalling and its possible causes, such as the cerebral endothelial glycocalyx and leukocyte adhesion molecules after depleting pericytes postnatally in mice. Moreover, we investigated hypoxia and gliosis as consequences of capillary stalling. Although there were no differences in the capillary structure and RBC flow, longitudinal optical coherence tomography angiography showed an increased number of stalled segments in capillaries after pericyte loss. Furthermore, the extent of the cerebral endothelial glycocalyx was decreased with increased expression of leukocyte adhesion molecules, suggesting enhanced interaction between leukocytes and endothelial cells. Finally, pericyte loss induced cerebral hypoxia and gliosis. Cumulatively, the results suggest that pericyte loss induces capillary stalling through increased interaction between leukocytes and endothelial cells in the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Pericyte Loss Decreases the Extent Of The Cerebral Endotheli...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pericyte Loss Leads to Capillary Stalling Through Increased Leukocyte-Endothelial Cell Interaction in the Brain

Choe

Yoon

Joo

et al. 2022

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the healthy murine brain, circulating leukocytes stall transiently in 0.4% of cerebral capillaries, possibly by interacting with the glycocalyx or selectins on ECs 128 , 172 – 174 ( Fig. 4 ).…”

Section: Immune Cell Control Of Blood Supply To the Cnsmentioning

confidence: 99%

Immune–vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood–brain barrier

2022

View full text Add to dashboard Cite

. Brain barriers are crucial sites for cerebral energy supply, waste removal, immune cell migration, and solute exchange, all of which maintain an appropriate environment for neuronal activity. At the capillary level, where the largest area of brain–vascular interface occurs, pericytes adjust cerebral blood flow (CBF) by regulating capillary diameter and maintain the blood–brain barrier (BBB) by suppressing endothelial cell (EC) transcytosis and inducing tight junction expression between ECs. Pericytes also limit the infiltration of circulating leukocytes into the brain where resident microglia confine brain injury and provide the first line of defence against invading pathogens. Brain “waste” is cleared across the BBB into the blood, phagocytosed by microglia and astrocytes, or removed by the flow of cerebrospinal fluid (CSF) through perivascular routes—a process driven by respiratory motion and the pulsation of the heart, arteriolar smooth muscle, and possibly pericytes. “Dirty” CSF exits the brain and is probably drained around olfactory nerve rootlets and via the dural meningeal lymphatic vessels and possibly the skull bone marrow. The brain is widely regarded as an immune-privileged organ because it is accessible to few antigen-primed leukocytes. Leukocytes enter the brain via the meninges, the BBB, and the blood-CSF barrier. Advances in genetic and imaging tools have revealed that neurological diseases significantly alter immune–brain barrier interactions in at least three ways: (1) the brain’s immune-privileged status is compromised when pericytes are lost or lymphatic vessels are dysregulated; (2) immune cells release vasoactive molecules to regulate CBF, modulate arteriole stiffness, and can plug and eliminate capillaries which impairs CBF and possibly waste clearance; and (3) immune–vascular interactions can make the BBB leaky via multiple mechanisms, thus aggravating the influx of undesirable substances and cells. Here, we review developments in these three areas and briefly discuss potential therapeutic avenues for restoring brain barrier functions.

show abstract

In vivo methods for imaging blood–brain barrier function and dysfunction

Harris

Asselin

Hinz

et al. 2022

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

The blood–brain barrier (BBB) is the interface between the central nervous system and systemic circulation. It tightly regulates what enters and is removed from the brain parenchyma and is fundamental in maintaining brain homeostasis. Increasingly, the BBB is recognised as having a significant role in numerous neurological disorders, ranging from acute disorders (traumatic brain injury, stroke, seizures) to chronic neurodegeneration (Alzheimer’s disease, vascular dementia, small vessel disease). Numerous approaches have been developed to study the BBB in vitro, in vivo, and ex vivo. The complex multicellular structure and effects of disease are difficult to recreate accurately in vitro, and functional aspects of the BBB cannot be easily studied ex vivo. As such, the value of in vivo methods to study the intact BBB cannot be overstated. This review discusses the structure and function of the BBB and how these are affected in diseases. It then discusses in depth several established and novel methods for imaging the BBB in vivo, with a focus on MRI, nuclear imaging, and high-resolution intravital fluorescence microscopy.

show abstract

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Cited by 18 publications

References 86 publications

Pericyte Loss Leads to Capillary Stalling Through Increased Leukocyte-Endothelial Cell Interaction in the Brain

Pericyte Loss Leads to Capillary Stalling Through Increased Leukocyte-Endothelial Cell Interaction in the Brain

Immune–vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood–brain barrier

In vivo methods for imaging blood–brain barrier function and dysfunction

Contact Info

Product

Resources

About