In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells

2021 ◽  
Author(s):  
Bárbara Sánchez-Dengra ◽  
Isabel González-Álvarez ◽  
Flavia Sousa ◽  
Marival Bermejo ◽  
Marta González-Álvarez ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Vitro Model ◽  
The Brain

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

scholarly journals A Gut-Brain Axis-on-a-Chip for studying transport across epithelial and endothelial barriers

2021 ◽  
Author(s):  
Min-Hyeok Kim ◽  
Donghyun Kim ◽  
Jong Hwan Sung
Keyword(s):  
Cognitive Abilities ◽  
In Vitro Model ◽  
Commensal Microbiota ◽  
Cell Responses ◽  
Chip Technology ◽  
Endothelial Barriers ◽  
Dietary Components ◽  
Vitro Model ◽  
The Brain

Recent research on Gut-Brain Axis (GBA) has suggested that the gut luminal environment, including the dietary components and commensal microbiota, could affect behavior, emotion, and cognitive abilities in the brain. The research on GBA has heavily relied on animal models, which makes the research challenging. Recent advances in organ-on-a-chip technology could be a solution for GBA research. In present work, we developed a modular microfluidic chip, where gut epithelial and brain endothelial cells were co-cultured to form the gut epithelial barrier and the Blood-Brain Barrier (BBB). Cell responses to microbial byproducts were examined by TEER measurement for each barrier, and we observed the transport of fluorescently labeled exosome across the gut barrier towards the BBB. Our results suggest this model can be used as a novel in vitro model of GBA for studying the interaction between the gut and the brain.

scholarly journals Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and impact on neuron biology.

2021 ◽  
Author(s):  
Thomas Mouveaux ◽  
Emmanuel Roger ◽  
Alioune Gueye ◽  
Fanny Eysert ◽  
Ludovic Huot ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
In Vitro Model ◽  
Brain Cell ◽  
Brain Cells ◽  
Specific Response ◽  
Cell Infection ◽  
Vitro Model ◽  
The Brain

Toxoplasma gondii is a eukaryotic parasite that form latent cyst in the brain of immunocompetent individuals. The latent parasites infection of the immune privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons long-term infection are unknown. It has long been known that T. gondii specifically differentiate into a latent form (bradyzoite) in neurons, but how the infected neuron is responding to the infection remain to be elucidated. We have established a new in vitro model resulting in the production of fully mature bradyzoites cysts in brain cells. Using dual, host and parasite, RNA-seq we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse. The establishment of this new in vitro model allows to investigate both the dynamics of the parasite differentiation and the specific response of neurons to the long term infection by this parasite.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

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