scholarly journals Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Francisco De Jesús Andino ◽  
Letitia Jones ◽  
Sanjay B. Maggirwar ◽  
Jacques Robert
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Blood Brain ◽  
The Brain

scholarly journals The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1237-1249 ◽  
Author(s):  
Ruiqing Kang ◽  
Marcin Gamdzyk ◽  
Cameron Lenahan ◽  
Jiping Tang ◽  
Sheng Tan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Vital Role ◽  
Dual Role ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
M2 Microglia ◽  
The Brain

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

Cadmium-induced alterations in blood- brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat

1996 ◽  
Vol 15 (5) ◽  
pp. 400-405 ◽  
Author(s):  
Arti Shukla ◽  
Girja S Shukla ◽  
RC Srimal
Keyword(s):  
Glutathione Peroxidase ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Albino Rats ◽  
Barrier Dysfunction ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

1 Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt) in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels by 76% ( P < 0.05) and 165% ( P < 0.001) respec tively at 30 and 90 days of exposure compared to controls. 2 Cadmium increased blood - brain barrier permeability of fluoroscein dye (24%, P < 0.02) and the levels ofbrain microvessel malondialdehyde (31%, P<0.01) at 90 days of exposure. However, these parameters did not alter significantly at 30 days of exposure. 3 Increased activities of microvessel superoxide dismu tase (18%, P<0.02), glutathione peroxidase (20%, P<0.01) and catalase (28%, P<0.01) were observed at 30 days of exposure. 4 The continuation of the Cd treatment for 90 days decreased the levels of superoxide dismutase (30%, P<0.001), glutathione peroxidase (23%, P<0.005), catalase (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P < 0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and ceruloplas min (13%, P<0.05) in the microvessal preparation compared to controls. 5 It appears that Cd-induced blood-brian barrier dysfunction may be related to the depletion of microvessel antioxidant substances along with in crease in lipid peroxidation at 90 days of exposure.

scholarly journals The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yiwei Wang ◽  
Huanhuan Sha ◽  
Leting Zhou ◽  
Yinan Chen ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Mast Cell ◽  
Blood Brain Barrier ◽  
Microglial Activation ◽  
Brain Barrier ◽  
Brain Disorders ◽  
Barrier Dysfunction ◽  
Cns Inflammation ◽  
Lps Challenge ◽  
Blood Brain ◽  
The Brain

Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

scholarly journals EXPERIMENTAL INTESTINAL DYSBIOSIS IN RATS INCREASES THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER AND INDUCES NEUROINFLAMMATION

2019 ◽  
Vol 19 (1S) ◽  
pp. 104-105
Author(s):  
V G Sergeyev ◽  
T N Sergeyeva
Keyword(s):  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Alpha Synuclein ◽  
Brain Barrier ◽  
Local Inflammation ◽  
Barrier Dysfunction ◽  
Cellular Mechanisms ◽  
Blood Brain ◽  
Intestinal Dysbiosis ◽  
The Brain

The mammalian intestinal microbiota consists of bacteria, fungi and viruses, including bacteriophages. This complex ecosystem has dynamic stability. It is assumed that changes in the composition of the microbiota can cause intestinal barrier dysfunction and the development of a number of pathologies, including neurodegenerative diseases accompanied by neuroinflammation. The molecular and cellular mechanisms underlying such a relationship remain poorly understood. We hypothesized that bacteriophages cause intestinal dysbiosis, increased intestinal permeability and local inflammation. Bacterial factors (endotoxins, zonulin-like proteins) and local inflammation products (cytokines, alpha-synuclein protein) can enter the circulation and increase the permeability of the blood-brain barrier (BBB), which will cause neuro-inflammation and damage to neurons. In this study, we observed an increase in BBB permeability and induction of neuroinflammation in the brain after rectal administration of a bacteriophage cocktail (Microgen, Russia). The permeability of the BBB was judged by the volume of the vital dye (Evans blue) emerging from the bloodstream into the brain parenchyma, and the development of the neuroinflammatory response by increasing the number of immunohistochemically stained microglial and astroglial cells.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

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.

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