Toward Standardization of a Lung New Approach Model for Toxicity Testing of Nanomaterials.

This study represents an attempt toward the standardization of pulmonary NAMs and the development of a novel approach for toxicity testing of nanomaterials. Laboratory comparisons are challenging yet essential for identifying existing limitations and proposing potential solutions. Lung cells cultivated and exposed at the air-liquid interface (ALI) more accurately represent the physiology of human lungs and pulmonary exposure scenarios than submerged cell and exposure models.

Systematic review of mechanistic evidence for TiO nanoparticle-induced lung carcinogenicity.

Nano-sized titanium dioxide particles (TiO NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO NPs in the lung are still unclear despite the vast number of and studies investigating TiO NPs. Here, we systematically reviewed the existing and mechanistic evidence of TiO NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens.

Advanced Respiratory Models for Hazard Assessment of Nanomaterials-Performance of Mono-, Co- and Tricultures.

Advanced in vitro models are needed to support next-generation risk assessment (NGRA), moving from hazard assessment based mainly on animal studies to the application of new alternative methods (NAMs). Advanced models must be tested for hazard assessment of nanomaterials (NMs). The aim of this study was to perform an interlaboratory trial across two laboratories to test the robustness of and optimize a 3D lung model of human epithelial A549 cells cultivated at the air-liquid interface (ALI).

Targeted deletion of Aqp4 promotes the formation of astrocytic gap junctions.

Aquaporin-4 (AQP4) is the predominant water channel in the brain and is expressed in high density in astrocytes. By fluxing water along osmotic gradients, AQP4 contributes to brain volume and ion homeostasis. Here we ask whether deletion of Aqp4 leads to upregulation of the gap junctional proteins connexin-43 (Cx43) and connexin-30 (Cx30).

Mechanisms underlying AQP4 accumulation in astrocyte endfeet.

The brain-blood interface holds the key to our understanding of how cerebral blood flow is regulated and how water and solutes are exchanged between blood and brain. The highly specialized astrocytic membranes that enwrap brain microvessels are salient constituents of the brain-blood interface. These endfoot membranes contain a distinct set of molecules that is anchored to the subendothelial basal lamina forming an endfoot-basal lamina junctional complex.

Postnatal development of the molecular complex underlying astrocyte polarization.

Astrocytes are highly polarised cells with processes that ensheath microvessels, cover the brain surface, and abut synapses. The endfoot membrane domains facing microvessels and pia are enriched with aquaporin-4 water channels (AQP4) and other members of the dystrophin associated protein complex (DAPC). Several lines of evidence show that loss of astrocyte polarization, defined by the loss of proteins that are normally enriched in astrocyte endfeet, is a common denominator of several neurological diseases such as mesial temporal lobe epilepsy, Alzheimer's disease, and stroke.

NF-κB activity in perinatal brain during infectious and hypoxic-ischemic insults revealed by a reporter mouse.

Infants suffering from infection or hypoxia-ischemia around the time of birth can develop brain damage resulting in life-long impairment such as cerebral palsy, epilepsy and cognitive disability. Inflammation appears to be an important contributor irrespective of whether the primary event is infection or hypoxia-ischemia. Activation of the transcription factor NF-κB is a hallmark of inflammation.

Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer's disease.

Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis.

A silk platform that enables electrophysiology and targeted drug delivery in brain astroglial cells.

Astroglial cell survival and ion channel activity are relevant molecular targets for the mechanistic study of neural cell interactions with biomaterials and/or electronic interfaces. Astrogliosis is the most typical reaction to in vivo brain implants and needs to be avoided by developing biomaterials that preserve astroglial cell physiological function. This cellular phenomenon is characterized by a proliferative state and altered expression of astroglial potassium (K(+)) channels.