Imaging effects of hyperosmolality on individual tricellular junctions

Huang, Kaixiang; Zhou, Li; Alanis, Kristen; Hou, Jianghui; Baker, Lane A.

doi:10.1039/c9sc05114g

Cited by 13 publications

(9 citation statements)

References 51 publications

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“…Perspiration-induced dehydration produces a decrease in plasma volume and extracellular water which leads to hyperosmolarity. Hyperosmolarity has been reported to enhance paracellular permeability in Caco-2 cells without damaging the cell membranes via cell shrinkage 51 and/or via hyperosmolar driven disruption of tight junctions 52 . This could explain the observed increase in intestinal permeability without intestinal damage in our study.…”

Section: Discussionmentioning

confidence: 99%

Sauna dehydration as a new physiological challenge model for intestinal barrier function

Rubio

Eriksson

Brummer

et al. 2021

Sci Rep

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The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

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Section: Discussionmentioning

confidence: 99%

Sauna dehydration as a new physiological challenge model for intestinal barrier function

Rubio

Eriksson

Brummer

et al. 2021

Sci Rep

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“…Mannitol is a hyperosmolar agent used in the treatment of brain trauma and is widely known to diminish the barrier function of the BBB. [ 65–67 ] Mannitol was introduced at the apical side of the BBB model and a clear decrease of the TEER value was observed (Figure 5d). After 90 min of mannitol treatment, the TEER value dropped by ≈40% of the original value, showing the paper/nanofiber‐based BBB model mimics observations for in vivo BBB to hyperosmotic conditions.…”

Section: Resultsmentioning

confidence: 96%

A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model

et al. 2021

Self Cite

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The blood–brain barrier (BBB) protects the central nervous system from toxins and pathogens in the blood by regulating permeation of molecules through the barrier interface. In vitro BBB models described to date reproduce some aspects of BBB functionality, but also suffer from incomplete phenotypic expression of brain endothelial traits, difficulty in reproducibility and fabrication, or overall cost. To address these limitations, a 3D BBB model based on a hybrid paper/nanofiber scaffold is described. The cell culture platform utilizes lens paper as a framework to accommodate 3D culture of astrocytes. An electrospun nanofiber layer is coated onto one face of the paper to mimic the basement membrane and support growth of an organized 2D layer of endothelial cells (ECs). Human induced pluripotent stem cell‐derived ECs and astrocytes are co‐cultured to develop a human BBB model. Morphological and spatial organization of model are validated with confocal microscopy. Measurements of transendothelial resistance and permeability demonstrate the BBB model develops a high‐quality barrier and responds to hyperosmolar treatments. RNA‐sequencing shows introduction of astrocytes both regulates EC tight junction proteins and improves endothelial phenotypes related to vasculogenesis. This model shows promise as a model platform for future in vitro studies of the BBB.

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“…In the central nervous system of mammals, the BBB is created at the level of the endothelial brain cells, where multiple protein complexes accumulate at the cell-junctions, restricting the paracellular diffusion of ions and other polar solutes, hence effectively blocking the penetration of macromolecules. Unfortunately, therapeutic hyperosmolar agents can reversibly open thigh junctions in the cerebrovascular endothelium, and their conductivity depends on the degree of plasma hyperosmolality [ 87 , 88 , 89 , 90 ]. An experimental study has shown a temporal induction of neuroinflammatory response following intracarotid infusion of mannitol [ 89 ].…”

Section: Plasma Hyperosmolality and The Blood–brain Barriermentioning

confidence: 99%

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

Dąbrowski

Siwicka-Gieroba

Robba

et al. 2021

JCM

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Hyperosmotic therapy is commonly used to treat intracranial hypertension in traumatic brain injury patients. Unfortunately, hyperosmolality also affects other organs. An increase in plasma osmolality may impair kidney, cardiac, and immune function, and increase blood–brain barrier permeability. These effects are related not only to the type of hyperosmotic agents, but also to the level of hyperosmolality. The commonly recommended osmolality of 320 mOsm/kg H2O seems to be the maximum level, although an increase in plasma osmolality above 310 mOsm/kg H2O may already induce cardiac and immune system disorders. The present review focuses on the adverse effects of hyperosmolality on the function of various organs.

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Imaging effects of hyperosmolality on individual tricellular junctions

Abstract: A nanoscale electrochemical imaging method was used to reveal heterogeneity present in conductance at epithelial cell junctions under hyperosmotic stress.

Cited by 13 publications

References 51 publications

Sauna dehydration as a new physiological challenge model for intestinal barrier function

Sauna dehydration as a new physiological challenge model for intestinal barrier function

A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

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