Microfluidic Systems: A 3D Biohybrid Real‐Scale Model of the Brain Cancer Microenvironment for Advanced In Vitro Testing (Adv. Mater. Technol. 10/2020)

Abstract Brain cancers remain one of the greatest medical challenges. The lack of experimentally tractable models that recapitulate brain structure/function represents a major impediment. Platforms that enable functional testing in high-fidelity models are urgently needed to accelerate the identification and translation of therapies to improve outcomes for patients suffering from brain cancer. In vitro assays are often too simple and artificial while in vivo studies can be time-intensive and complicated. Our live, organotypic brain slice platform can be used to seed and grow brain cancer cell lines, allowing us to bridge the existing gap in models. These tumors can rapidly establish within the brain slice microenvironment, and morphologic features of the tumor can be seen within a short period of time. The growth, migration, and treatment dynamics of tumors seen on the slices recapitulate what is observed in vivo yet is missed by in vitro models. Additionally, the brain slice platform allows for the dual seeding of different cell lines to simulate characteristics of heterogeneous tumors. Furthermore, live brain slices with embedded tumor can be generated from tumor-bearing mice. This method allows us to quantify tumor burden more effectively and allows for treatment and retreatment of the slices to understand treatment response and resistance that may occur in vivo. This brain slice platform lays the groundwork for a new clinically relevant preclinical model which provides physiologically relevant answers in a short amount of time leading to an acceleration of therapeutic translation.

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Effect of pH and inhibitors on beta-amyloid fibril assembly

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166221 ◽

1996 ◽

Vol 54 ◽

pp. 752-753

Author(s):

Beverly E. Maleeff ◽

Timothy K. Hart ◽

Stephen J. Wood ◽

Ronald Wetzel

Keyword(s):

Amyloid Fibril ◽

Peptide Fragment ◽

Hydrophobic Peptides ◽

Amyloid Fibril Formation ◽

Effects Of Ph ◽

Severity Of The Disease ◽

Kinetics Of ◽

The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

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Urokinase Evaluated with the Experimental Radioactive Embolus

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654164 ◽

1967 ◽

Vol 17 (03/04) ◽

pp. 405-411

Author(s):

M Hume

Keyword(s):

Animal Experiment ◽

Blood Clot ◽

In Vitro Testing ◽

Effective Agent

SummaryUrokinase and urokinase-activated plasmin have been given to the dog and rabbit. A thrombolytic state has been induced. Purified urokinase has induced lysis of the experimental radioactive blood clot embolus in the circulation. Demonstration of effectiveness in this animal experiment is hampered by inhibition of the agents in the circulation to a degree much greater than was noted in previous experiments with streptokinase. In vitro testing indicates that under proper conditions urokinase will be an effective agent in the treatment of human thromboembolism.

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Acoustics on a Real Scale Model: Application to Fractured Media

Revue de l Institut Français du Pétrole ◽

10.2516/ogst:1993022 ◽

1993 ◽

Vol 48 (4) ◽

pp. 347-357

Author(s):

J. L. Mari ◽

P. Gaudiani

Keyword(s):

Fractured Media ◽

Scale Model ◽

Model Application ◽

Real Scale

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Involvement of cytochrome P450 2D in the formation of serotonin in the brain: in vivo and in vitro study

10.26226/morressier.5785edc6d462b80296c9934c ◽

2016 ◽

Author(s):

Anna Haduch

Keyword(s):

Cytochrome P450 ◽

In Vitro Study ◽

Vitro Study ◽

The Brain

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Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

Current Drug Delivery ◽

10.2174/1567201817666200210120950 ◽

2020 ◽

Vol 17 (3) ◽

pp. 229-245

Author(s):

Gang Wang ◽

Junjie Wang ◽

Rui Guan

Keyword(s):

Drug Delivery ◽

Brain Tumor ◽

Oral Delivery ◽

Safe Delivery ◽

Drug Delivery Vehicles ◽

Therapeutic Benefits ◽

Delivery Vehicles ◽

The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

Current Alzheimer Research ◽

10.2174/1567205017666201130085853 ◽

2020 ◽

Vol 17 ◽

Author(s):

Reem Habib Mohamad Ali Ahmad ◽

Marc Fakhoury ◽

Nada Lawand

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

In Vivo Studies ◽

Key Factors ◽

Potential Benefits ◽

Preclinical And Clinical Studies ◽

The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

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Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2703 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2703-2712 ◽

Cited By ~ 21

Author(s):

Stephen M. Johnson ◽

Julia E. R. Wilkerson ◽

Daniel R. Henderson ◽

Michael R. Wenninger ◽

Gordon S. Mitchell

Keyword(s):

Brain Stem ◽

Respiratory Activity ◽

Dependent Manner ◽

Frequency Increase ◽

Burst Frequency ◽

Bath Application ◽

Burst Amplitude ◽

Dose Dependent ◽

The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

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Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽

10.3390/molecules25092104 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2104 ◽

Cited By ~ 1

Author(s):

Eleonora Ficiarà ◽

Shoeb Anwar Ansari ◽

Monica Argenziano ◽

Luigi Cangemi ◽

Chiara Monge ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Tumors ◽

Ad Hoc ◽

Superparamagnetic Iron Oxide ◽

Conventional Radiotherapy ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri ◽

The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

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