scholarly journals CdSe/ZnS Core-Shell-Type Quantum Dot Nanoparticles Disrupt the Cellular Homeostasis in Cellular Blood–Brain Barrier Models

2021 ◽  
Vol 22 (3) ◽  
pp. 1068
Author(s):  
Katarzyna Dominika Kania ◽  
Waldemar Wagner ◽  
Łukasz Pułaski
Keyword(s):  
Gene Expression ◽  
Quantum Dot ◽  
Blood Brain Barrier ◽  
Protein Gene ◽  
Brain Barrier ◽  
Core Shell ◽  
Cellular Homeostasis ◽  
Blood Brain ◽  
Shell Type ◽  
The Impact

Two immortalized brain microvascular endothelial cell lines (hCMEC/D3 and RBE4, of human and rat origin, respectively) were applied as an in vitro model of cellular elements of the blood–brain barrier in a nanotoxicological study. We evaluated the impact of CdSe/ZnS core-shell-type quantum dot nanoparticles on cellular homeostasis, using gold nanoparticles as a largely bioorthogonal control. While the investigated nanoparticles had surprisingly negligible acute cytotoxicity in the evaluated models, a multi-faceted study of barrier-related phenotypes and cell condition revealed a complex pattern of homeostasis disruption. Interestingly, some features of the paracellular barrier phenotype (transendothelial electrical resistance, tight junction protein gene expression) were improved by exposure to nanoparticles in a potential hormetic mechanism. However, mitochondrial potential and antioxidant defences largely collapsed under these conditions, paralleled by a strong pro-apoptotic shift in a significant proportion of cells (evidenced by apoptotic protein gene expression, chromosomal DNA fragmentation, and membrane phosphatidylserine exposure). Taken together, our results suggest a reactive oxygen species-mediated cellular mechanism of blood–brain barrier damage by quantum dots, which may be toxicologically significant in the face of increasing human exposure to this type of nanoparticles, both intended (in medical applications) and more often unintended (from consumer goods-derived environmental pollution).

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

scholarly journals Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0144215 ◽  
Author(s):  
Gerard Honig ◽  
Simone Mader ◽  
Huiyi Chen ◽  
Amit Porat ◽  
Mahendar Ochani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vagus Nerve ◽  
Blood Brain Barrier ◽  
Polymicrobial Sepsis ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Blood—Brain Barrier Genomics

2001 ◽  
Vol 21 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Jian Yi Li ◽  
Ruben J. Boado ◽  
William M. Pardridge
Keyword(s):  
Gene Expression ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Specific Gene ◽  
Microvascular Endothelium ◽  
Tissue Specific ◽  
Tissue Specific Gene ◽  
Specific Gene Expression ◽  
Blood Brain ◽  
Tester Cdna

The blood–brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction–based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IκB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level.

Intracerebral Hemorrhage and Diabetes Mellitus: Blood-Brain Barrier Disruption, Pathophysiology, and Cognitive Impairments

2021 ◽  
Vol 20 ◽  
Author(s):  
Ghaith A. Bahadar ◽  
Zahoor A Shah
Keyword(s):  
Diabetes Mellitus ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Comorbid Condition ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
The Impact

: There is a surge in diabetes incidence with an estimated 463 million individuals been diagnosed worldwide. Diabetes Mellitus (DM) is a major stroke-related comorbid condition that increases the susceptibility of disabling post-stroke outcomes. Although less common, intracerebral hemorrhage (ICH) is the most dramatic subtype of stroke that is associated with higher mortality, particularly in DM population. Previous studies have focused mainly on the impact of DM on ischemic stroke. Few studies have focused on impact of DM on ICH and discussed the blood-brain barrier disruption, brain edema, and hematoma formation. However, more recently, investigating the role of oxidative damage and reactive oxygen species (ROS) production in preclinical studies involving DM-ICH animal models has gained attention. But, little is known about the correlation between neuroinflammatory processes, glial cells activation, and peripheral immune cell invasion with DM-ICH injury. DM and ICH patients experience impaired abilities in multiple cognitive domains by relatively comparable mechanisms, which could get exacerbated in the setting of comorbidities. In this review, we discuss both the pathology of DM as a comorbid condition for ICH and the potential molecular therapeutic targets for the clinical management of the ICH and its recovery.

Benzophenone-3 Passes Through the Blood-Brain Barrier, Increases the Level of Extracellular Glutamate, and Induces Apoptotic Processes in the Hippocampus and Frontal Cortex of Rats

2019 ◽  
Vol 171 (2) ◽  
pp. 485-500 ◽  
Author(s):  
Bartosz Pomierny ◽  
Weronika Krzyżanowska ◽  
Żaneta Broniowska ◽  
Beata Strach ◽  
Beata Bystrowska ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Blood Brain Barrier ◽  
Brain Structures ◽  
Glutamate Transporters ◽  
Brain Barrier ◽  
Short Term ◽  
Extracellular Glutamate ◽  
Blood Brain ◽  
The Impact ◽  
The Brain

Abstract Benzophenone-3 is the most commonly used UV filter. It is well absorbed through the skin and gastrointestinal tract. Its best-known side effect is the impact on the function of sex hormones. Little is known about the influence of BP-3 on the brain. The aim of this study was to show whether BP-3 crosses the blood-brain barrier (BBB), to determine whether it induces nerve cell damage in susceptible brain structures, and to identify the mechanism of its action in the central nervous system. BP-3 was administered dermally during the prenatal period and adulthood to rats. BP-3 effect on short-term and spatial memory was determined by novel object and novel location recognition tests. BP-3 concentrations were assayed in the brain and peripheral tissues. In brain structures, selected markers of brain damage were measured. The study showed that BP-3 is absorbed through the rat skin, passes through the BBB. BP-3 raised oxidative stress and induced apoptosis in the brain. BP-3 increased the concentration of extracellular glutamate in examined brain structures and changed the expression of glutamate transporters. BP-3 had no effect on short-term memory but impaired spatial memory. The present study showed that dermal BP-3 exposure may cause damage to neurons what might be associated with the increase in the level of extracellular glutamate, most likely evoked by changes in the expression of GLT-1 and xCT glutamate transporters. Thus, exposure to BP-3 may be one of the causes that increase the risk of developing neurodegenerative diseases.

scholarly journals Immunolocalization of Heat Shock Protein after Fluid Percussive Brain Injury and Relationship to Breakdown of the Blood-Brain Barrier

1993 ◽  
Vol 13 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Hirokazu Tanno ◽  
Russ P. Nockels ◽  
Lawrence H. Pitts ◽  
Linda J. Noble
Keyword(s):  
Brain Injury ◽  
Head Injury ◽  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Time Course ◽  
Cortical Layer ◽  
Brain Barrier ◽  
Impact Site ◽  
Blood Brain ◽  
The Impact

We have previously developed a model of mild, lateral fluid percussive head injury in the rat and demonstrated that although this injury produced minimal hemorrhage, breakdown of the blood–brain barrier was a prominent feature. The relationship between posttraumatic blood–brain barrier disruption and cellular injury is unclear. In the present study we examined the distribution and time course of expression of the stress protein HSP72 after brain injury and compared these findings with the known pattern of breakdown of the blood–brain barrier after a similar injury. Rats were subjected to a lateral fluid percussive brain injury (4.8–5.2 atm, 20 ms) and killed at 1, 3, and 6 h and 1,3, and 7 days after injury. HSP72-like immunoreactivity was evaluated in sections of brain at the light-microscopic level. The earliest expression of HSP72 occurred at 3 h postinjury and was restricted to neurons and glia in the cortex surrounding a necrotic area at the impact site. By 6 h, light immunostaining was also noted in the pia-arachnoid adjacent to the impact site and in certain blood vessels that coursed through the area of necrosis. Maximal immunostaining was observed by 24 h postinjury, and was primarily associated with the cortex immediately adjacent to the region of necrosis at the impact site. This region consisted of darkly immunostained neurons, glia, and blood vessels. Immunostaining within the region of necrosis was restricted to blood vessels. HSP72-like immunoreactivity was also noted in a limited number of neurons and glia in other brain regions, including the parasagittal cortex, deep cortical layer VI, and CA3 in the posterior hippocampus. Immunoreactive cells in these areas were not apparent until 24 h postinjury. By 7 days postinjury, HSP72-like immunoreactivity was minimal or absent in these injured brains and notable cell loss was apparent only in the impact site. This study demonstrates an early and pronounced expression of HSP72 at the impact site and a more delayed and less prominent expression of this protein in other regions of the brain. These findings parallel the temporal and regional pattern of breakdown of the blood–brain barrier after a similar head injury.

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