scholarly journals Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine strains in anin cellulomodel of human blood-brain barrier

2019 ◽  
Author(s):  
Cécile Khou ◽  
Marco Aurelio Díaz-Salinas ◽  
Anaelle da Costa ◽  
Christophe Préhaud ◽  
Patricia Jeannin ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Japanese Encephalitis ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cells ◽  
Brain Barrier ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Viral Determinants

ABSTRACTJapanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that JEV gets access to the central nervous system (CNS) as a consequence of a preceding inflammatory process which leads to the blood-brain barrier (BBB) disruption and viral neuroinvasion. However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross anin cellulohuman BBB model consisting of hCMEC/D3 human endothelial cells cultivated on permeable inserts above SK-N-SH human neuroblastoma cells. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post-addition. Furthermore, this BBB model was able to discriminate between the virulent RP9 and the vaccine SA14-14-2 strains, as demonstrated by the presence of almost 10 times more RP9 infectious particles that crossed the BBB than SA14-14 particles at a high MOI. Besides contributing to the understanding of early events in JEV neuroinvasion, thisin celluloBBB model represents a suitable and useful system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB at early times of neuroinvasion.

scholarly journals Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine viral strains in an in vitro model of human blood-brain barrier

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252595
Author(s):  
Cécile Khou ◽  
Marco Aurelio Díaz-Salinas ◽  
Anaelle da Costa ◽  
Christophe Préhaud ◽  
Patricia Jeannin ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Japanese Encephalitis ◽  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Vitro Model ◽  
Viral Determinants

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that, as a consequence of the inflammatory process during JEV infection, there is disruption of the blood-brain barrier (BBB) tight junctions that in turn allows the virus access to the central nervous system (CNS). However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross an in vitro human BBB model. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post viral addition. Furthermore, we find that almost 10 times more RP9 infectious particles than SA14-14 cross the model BBB, indicating this BBB model discriminates between the virulent RP9 and the vaccine SA14-14-2 strains of JEV. Beyond contributing to the understanding of early events in JEV neuroinvasion, we demonstrate this in vitro BBB model can be used as a system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB during early times of neuroinvasion.

scholarly journals Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

2021 ◽  
Vol 22 (7) ◽  
pp. 3356
Author(s):  
Manon Leclerc ◽  
Stéphanie Dudonné ◽  
Frédéric Calon
Keyword(s):  
Natural Products ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Omega 3 ◽  
Indirect Pathway ◽  
Brain Functions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Peripheral Metabolism

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.

scholarly journals Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

2019 ◽  
Vol 20 (3) ◽  
pp. 571 ◽  
Author(s):  
Shotaro Michinaga ◽  
Yutaka Koyama
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secondary Damage ◽  
The Central Nervous System ◽  
Bbb Permeability ◽  
Novel Therapeutic Strategies ◽  
Glial Derived Neurotrophic Factor ◽  
Endothelial Growth Factors

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

scholarly journals Slowly Changing Bioelectric Potentials Associated With the Blood-Brain Barrier

1958 ◽  
Vol 195 (1) ◽  
pp. 7-22 ◽  
Author(s):  
Robert D. Tschirgi ◽  
J. Langdon Taylor
Keyword(s):  
Cerebral Cortex ◽  
Blood Brain Barrier ◽  
Interstitial Fluid ◽  
Brain Barrier ◽  
Membrane Diffusion ◽  
Arterial Blood ◽  
Blood Ph ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Bioelectric Potentials

A slowly changing bioelectric potential difference (P.D.) is measured in rats, rabbits, cats and dogs between various regions of the central nervous system (CNS) and the blood within the jugular vein. It is shown that the CNS-blood P.D. is very sensitive to alterations in alveolar CO2 tension, but this relationship is dependent upon the H+ concentration rather than CO2 per se. Whereas increasing intravenous H+ concentration increases CNS positivity, topical application of acid solutions directly to the cerebral cortex decreases CNS positivity. The same relationship is found for intravenous and topical K+. Anoxia and circulatory failure produce CNS negative deflections, often exceeding 15 mv, which do not return to zero for over 24 hours after death. Simultaneous measurements of arterial blood pH, cerebral cortex pH and CNS-blood P.D. reveal the following relationship among these variables: ΔP.D. = κ Δ log10 [H+]a/[H+]i where [H+]a is the H+ concentration of the arterial blood and [H+]i is the H+ concentration of the CNS interstitial fluid. For the CNS-blood P.D. between cerebral cortex and jugular blood of rabbits and rats, κ is found to be 29 ± 5. These results are interpreted as indicating a source of emf across the pan-vascular blood-brain barrier which resembles a membrane diffusion potential. The blood-brain barrier is postulated to be more permeable to H+ and K+ than to anions and other cations.

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