Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging

Salman, Mootaz M.; Marsh, Graham; Küsters, Ilja; Delincé, Matthieu; Caprio, Giuseppe Di; Upadhyayula, Srigokul; Nola, Giovanni de; Hunt, Ronan; Ohashi, Kazuka G.; Gray, Taylor J.; Shimizu, Fumitaka; Sano, Yuichi; Kanda, Takashi; Obermeier, Birgit; Kirchhausen, Tom

doi:10.3389/fbioe.2020.573775

Cited by 93 publications

(68 citation statements)

References 66 publications

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“…Another development, which can ease investigation of PE pathomechanism, was made by Salman et al, who created an microvessel-on-chip open microfluid model [ 81 ]. This model allows to create in vitro microvasculature from endothelial cells and control fluid flow through these vessels, and most importantly, observe these vessels with high resolution imaging modalities, such as electron microscopy, fluorescence imaging, etc.…”

Section: Perspectivesmentioning

confidence: 99%

“…This model allows to create in vitro microvasculature from endothelial cells and control fluid flow through these vessels, and most importantly, observe these vessels with high resolution imaging modalities, such as electron microscopy, fluorescence imaging, etc. [ 81 ]. If it will be able to apply this method to the spiral arteries model, it could allow for real time observation of spiral arteries remodeling, which is a key process in placentation and, if pathological, in PE development.…”

Section: Perspectivesmentioning

confidence: 99%

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The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

Socha

Malinowski

Puk

et al. 2021

IJMS

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Preeclampsia is one of the three leading causes of maternal morbidity and mortality worldwide. It afflicts 2–8% of pregnancies and is the most common cause of gestational hypertension. This article is focused on nuclear factor kappa B (NF-κB), its role in normal and pathological spiral arteries remodelling and development of preeclampsia, with evaluation if it is a promising therapeutic target. NF-κB is a key mediator of placentation. Since insemination, it stimulates production of proinflammatory cytokines by the uterine epithelium, which leads to activation of macrophages, uterine natural killer cells (uNKs), and other leukocytes. The trophoblast/uNK/macrophage crosstalk is crucial for implantation and spiral arteries remodeling, and NF-κB regulates that process through modification of cytokine expression, as well as cell phenotype and function. In the course of preeclampsia, the remodeling processes is disturbed by excessive inflammation and increased NF-κB activation. The pathological remodeling leads to uteroplacental dysfunction, release of proinflammatory cytokines into the maternal circulation, endothelial stress, and development of preeclampsia. The analysis of genetic and environmental inductors of NF-κB helps to distinguish preeclampsia risk groups. Furthermore, a selective inhibition of NF-κB or NF-κB activating pathways alleviates symptoms of preeclampsia in rat models; therefore, this could be an efficient therapeutic option.

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Section: Perspectivesmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

Socha

Malinowski

Puk

et al. 2021

IJMS

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“…Both in vitro modeling and optical imaging fields were developed progressively. Future studies based on advanced tools and platforms, such as humanized three-dimensional models, organoids with autonomous developmental systems and the blood-brain barrier microvessel-on-a-chip would promote answering mechanistic questions [104,105].…”

Section: Discussionmentioning

confidence: 99%

The Ketamine Antidepressant Story: New Insights

Alshammari

2020

Molecules

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Ketamine is a versatile agent primarily utilized as a dissociative anesthetic, which acts by blocking the excitatory receptor N-methyl-d-aspartate receptor (NMDA). It functions to inhibit the current of both Na+ and K+ voltage-gated channels, thus preventing serotonin and dopamine reuptake. Studies have indicated that administering a single subanesthetic dose of ketamine relieves depression rapidly and that the effect is sustained. For decades antidepressant agents were based on the monoamine theory. Although ketamine may not be the golden antidepressant, it has opened new avenues toward mechanisms involved in the pathology of treatment-resistant depression and achieving rapid antidepressant effects. Thus, preclinical studies focusing on deciphering the molecular mechanisms involved in the antidepressant action of ketamine will assist in the development of a new antidepressant. This review was conducted to elucidate the emerging pathways that can explain the complex dose-dependent mechanisms achieved by administering ketamine to treat major depressive disorders. Special attention was paid to reviewing the literature on hydroxynorketamines, which are ketamine metabolites that have recently attracted attention in the context of depression.

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“…However, it is very difficult to dissect each type of cell into different scenarios in animals. Alternatively, we will adopt new innovative tools, such as a humanized 3D self-organized model and organoids/organ on a chip platform to especially enable advanced optical imaging [35,36], for the next step.…”

Section: Discussionmentioning

confidence: 99%

Role of HMGB1/TLR4 Axis in Ischemia/Reperfusion-Impaired Extracellular Glutamate Clearance in Primary Astrocytes

Lin

Chen

Wei

2020

Cells

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(1) Background: Abnormal accumulation of extracellular glutamate can occur as dysfunction of astrocytic glutamate transporters, which has been linked to ischemic brain injury. Excessive extracellular glutamate-induced abnormal excitotoxicity is the major cause of secondary neuronal damage after cerebral ischemia/reperfusion. However, the definite mechanism of impaired astrocytic glutamate reuptake remains unclear. (2) Methods: We investigated the mechanism of the HMGB1/TLR4 axis in extracellular glutamate clearance in primary astrocytes exposed to ischemia/reperfusion by using OGD/R (oxygen-glucose deprivation/reoxygenation) model. (3) Results: OGD/R insult activated the HMGB1/TLR4 axis for reducing the activity of glutamate clearance by inhibiting GLAST (glutamate aspartate transporter) expression in primary astrocytes. Interestingly, OGD/R-untreated astrocytes showed impairment of glutamate clearance after exposure to exogenous HMGB1 or conditioned medium from OGD/R-treated astrocytes culture. Inhibition of HMGB1 or TLR4 effectively prevented impaired glutamate clearance, which was induced by OGD/R, exogenous HMGB1, or conditioned medium from OGD/R-treated astrocytes. Furthermore, glycyrrhizic acid attenuated OGD/R-induced impairment of astrocytic glutamate clearance mediated by the HMGB1-TLR4 axis. (4) Conclusion: The HMGB1/TLR4 axis is a potential target for the treatment of post-ischemic excitotoxicity caused by GLAST dysfunction in astrocytes.

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Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging

Cited by 93 publications

References 66 publications

The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

The Role of NF-κB in Uterine Spiral Arteries Remodeling, Insight into the Cornerstone of Preeclampsia

The Ketamine Antidepressant Story: New Insights

Role of HMGB1/TLR4 Axis in Ischemia/Reperfusion-Impaired Extracellular Glutamate Clearance in Primary Astrocytes

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