The blood–brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from the peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, the blood–brain barrier forms the neurovascular unit. Upon neuroinflammation, this barrier becomes leaky, allowing molecules and cells to enter the brain and to potentially harm the tissue of the central nervous system. Despite the significance of animal models in research, they may not always adequately reflect human pathophysiology. Therefore, human models are needed. This review will provide an overview of the blood–brain barrier in terms of both health and disease. It will describe all key elements of the in vitro models and will explore how different compositions can be utilized to effectively model a variety of neuroinflammatory conditions. Furthermore, it will explore the existing types of models that are used in basic research to study the respective pathologies thus far.

Blood-Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models.

The blood-brain barrier (BBB) restricts paracellular and transcellular diffusion of compounds and is part of a dynamic multicellular structure known as the “neurovascular unit” (NVU), which strictly regulates the brain homeostasis and microenvironment. Several neuropathological conditions (e.g., Parkinson’s disease and Alzheimer’s disease), are associated with BBB impairment yet the exact underlying pathophysiological mechanisms remain unclear. In total, 90% of drugs that pass animal testing fail human clinical trials, in part due to inter-species discrepancies. Thus, in vitro human-based models of the NVU are essential to better understand BBB mechanisms; connecting its dysfunction to neuropathological conditions for more effective and improved therapeutic treatments. Herein, we developed a biomimetic tri-culture NVU in vitro model consisting of 3 human-derived cell lines: human cerebral micro-vascular endothelial cells (hCMEC/D3), human 1321N1 (astrocyte) cells, and human SH-SY5Y neuroblastoma cells. The cells were grown in Transwell hanging inserts in a variety of configurations and the optimal setup was found to be the comprehensive tri-culture model, where endothelial cells express typical markers of the BBB and contribute to enhancing neural cell viability and neurite outgrowth. The tri-culture configuration was found to exhibit the highest transendothelial electrical resistance (TEER), suggesting that the cross-talk between astrocytes and neurons provides an important contribution to barrier integrity. Lastly, the model was validated upon exposure to several soluble factors [e.g., Lipopolysaccharides (LPS), sodium butyrate (NaB), and retinoic acid (RA)] known to affect BBB permeability and integrity. This in vitro biological model can be considered as a highly biomimetic recapitulation of the human NVU aiming to unravel brain pathophysiology mechanisms as well as improve testing and delivery of therapeutics.

/pdf/a-human-derived-neurovascular-unit-in-vitro-model-to-study-13kvrbj8.pdf

A human-derived neurovascular unit in vitro model to study the effects of cellular cross-talk and soluble factors on barrier integrity

In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cells (HBMVEC) and immortalized pericytes, both of human origin. The TTFields at a frequency of 100 kHz administered for 72 h increased the permeability of our human-derived BBB model. The integrity of the BBB had already recovered 48 h post-TTFields, which is earlier than that observed in cerebEND. The data presented herein validate the previously observed effects of TTFields in murine models. Moreover, due to the fact that human cell-based in vitro models more closely resemble patient-derived entities, our findings are highly relevant for pre-clinical studies.

/pdf/tumor-treating-fields-ttfields-induce-cell-junction-1rfiasl5.pdf

Tumor Treating Fields (TTFields) Induce Cell Junction Alterations in a Human 3D In Vitro Model of the Blood-Brain Barrier

Induction heating (IH) is an environmentally friendly solution for heating and melting processes. The required high-frequency magnetic field is accomplished through frequency controllers. Direct frequency controllers (DFC) are preferred to dual converters as they have low conversion losses, compact size, and simple circuit arrangement due to low component count. Numerous frequency controllers with complex switching algorithms are employed in the induction heating process. They have a complicated circuit arrangement, and complex control as their switching sequences have to synchronize with source voltage that requires the zero-crossing detection of the input voltage. They also have a shoot-through problem and poor power quality. Therefore, this research proposes a novel frequency controller with a low count of six controlled switching devices without a zero-crossing detector (ZCD) having a simple control arrangement. The required switching signals are simply generated by using any pulse-width-modulated (PWM) generator. The performance of the proposed topology is verified through simulation results obtained using the MATLAB/Simulink environment and experimental setup.

https://www.mdpi.com/2079-9292/9/3/430/pdf

A New Single-Phase Direct Frequency Controller Having Reduced Switching Count without Zero-Crossing Detector for Induction Heating System

LED lamps have many advantages in comparison with incandescent lamps, halogen lamps and compact fluorescent light lamps. Although produce harmonic pollution due to the drivers used for their power supply, they are becoming increasingly used nowadays. This paper presents a study of the harmonics from dimmable LED lamps, using reconfigurable CompactRIO system. Various available dimmable LEDs were tested. With CompactRIO, we can rapidly build an embedded control and acquisition system that can analyses the harmonics from dimmable LED lamps.

The study of harmonics from dimmable LED lamps, using CompactRIO

The paper presents two high-performance single-phase AC chopper circuits which perform AC-AC bidirectional direct conversion;one of them contains resistive loads and the other one is for inductive loads. It includes useful equations for chopper design. The correctfunctioning is tested by simulation. DOI: http://dx.doi.org/10.5755/j01.eee.18.10.1305

/pdf/direct-ac-ac-step-down-single-phase-converter-with-improved-3e44gi0to2.pdf

Direct AC-AC Step-Down Single-Phase Converter with Improved Performances

This paper introduces and studies a boost AC-AC converter circuit that can be used to supply power to the 220V receivers in the 110V grids or to increase and adjust voltage at the end ...

Single-Phase Direct Boost AC-AC Converter

The paper presents a single-phase direct AC-AC boost converter. The circuit of the converter is simple and it has good performances, irrespective of the load nature. The adequate funct ...

Single-Phase Direct AC-AC Boost Converter

The study proposes and analyses a new circuit of direct AC–AC converter that can perform a bidirectional energy flow. The authors calculated the equations governing the functioning of the circuit. The adequate functioning and high performance of the circuit (the efficiency and waveform of the absorbed input current) were tested both by simulation and experimentally.

https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/iet-pel.2013.0730

Single-phase direct AC–AC step-down converter

A Novel Method for Accurate Determination of the Output Voltage Ripple of DC Converters in All Operating Modes

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