REST-dependent glioma progression occurs independently of the repression of the long non-coding RNA HAR1A.

The long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor. In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts as an oncogene and is a potential therapeutic target.

A hydrogel model of the human blood-brain barrier using differentiated stem cells.

An in vitro model of the human blood-brain barrier was developed, based on a collagen hydrogel containing astrocytes, overlaid with a monolayer of endothelium, differentiated from human induced pluripotent stem cells (hiPSCs). The model was set up in transwell filters allowing sampling from apical and basal compartments. The endothelial monolayer had transendothelial electrical resistance (TEER) values >700Ω.

Nanocarriers for Delivery of Oligonucleotides to the CNS.

Nanoparticles with oligonucleotides bound to the outside or incorporated into the matrix can be used for gene editing or to modulate gene expression in the CNS. These nanocarriers are usually optimised for transfection of neurons or glia. They can also facilitate transcytosis across the brain endothelium to circumvent the blood-brain barrier.

Tissue distribution and cellular localization of gold nanocarriers with bound oligonucleotides.

The aim of the study was to determine how the addition of a DNA oligonucleotide cargo to 3-nm gold glyconanoparticles would affect tissue distribution. Gold glyconanoparticles with 1-6 covalently bound oligonucleotides (40 nt dsDNA) were injected into rats and allowed to circulate for 10 min. Organs were harvested and gold quantitated by inductively coupled plasma mass spectrometry.

Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus.

Blood-brain barrier (BBB) breakdown occurs in aging and neurodegenerative diseases. Although age-associated alterations have previously been described, most studies focused in male brains; hence, little is known about BBB breakdown in females. This study measured ultrastructural features in the aging female BBB using transmission electron microscopy and 3-dimensional reconstruction of cortical and hippocampal capillaries from 6- and 24-month-old female C57BL/6J mice.

Gold nanocarriers for transport of oligonucleotides across brain endothelial cells.

Treatment of diseases that affect the CNS by gene therapy requires delivery of oligonucleotides to target cells within the brain. As the blood brain barrier prevents movement of large biomolecules, current approaches involve direct injection of the oligonucleotides, which is invasive and may have only a localised effect. The aim of this study was to investigate the potential of 2 nm galactose-coated gold nanoparticles (NP-Gal) as a delivery system of oligonucleotides across brain endothelium.

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer's disease: in vitro and in vivo studies.

Objective: The first aim of this study was to develop a nanocarrier that could transport the peroxisome proliferator-activated receptor agonist, pioglitazone (PGZ) across brain endothelium and examine the mechanism of nanoparticle transcytosis. The second aim was to determine whether these nanocarriers could successfully treat a mouse model of Alzheimer's disease (AD).

Methods: PGZ-loaded nanoparticles (PGZ-NPs) were synthesized by the solvent displacement technique, following a factorial design using poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG).

Transport of Gold Nanoparticles by Vascular Endothelium from Different Human Tissues.

The selective entry of nanoparticles into target tissues is the key factor which determines their tissue distribution. Entry is primarily controlled by microvascular endothelial cells, which have tissue-specific properties. This study investigated the cellular properties involved in selective transport of gold nanoparticles (<5 nm) coated with PEG-amine/galactose in two different human vascular endothelia.

Localization and mobility of glucose-coated gold nanoparticles within the brain.

Aim: To identify the localization of glucose-coated gold nanoparticles within cells of the brain after intravascular infusion which may point to the mechanism by which they cross the blood-brain barrier.

Materials & Methods: Tissue distribution of the nanoparticles was measured by inductively-coupled-mass spectrometry and localization within the brain by histochemistry and electron microscopy.

Results & Conclusion: Nanoparticles were identified within neurons and glial cells more than 10 μm from the nearest microvessel within 10 min of intracarotid infusion.

A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions.

The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry.

Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes.

Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues.

The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium.