scholarly journals Fetal Central Nervous System Derived Extracellular Vesicles: Potential for Non-invasive Tracking of Viral Mediated Fetal Brain Injury

2021 ◽  
Vol 1 ◽  
Author(s):  
Laura Goetzl ◽  
Angela J. Stephens ◽  
Yechiel Schlesinger ◽  
Nune Darbinian ◽  
Nana Merabova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Viral Infection ◽  
Extracellular Vesicles ◽  
First Trimester ◽  
Neurologic Outcome ◽  
Clinical Population ◽  
Non Invasive ◽  
Fetal Infection

Introduction: Extracellular vesicles derived from the fetal central nervous system (FCNSEs) can be purified from maternal serum or plasma using the protein Contactin-2/TAG1that is expressed almost exclusively by developing neurons in the hippocampus, cerebral cortex and cerebellum. We hypothesized that fetal CNSEs could be used to non-invasively detect and quantify viral mediated in-utero brain injury in the first trimester.Materials and Methods: First trimester maternal samples were collected from a human clinical population infected with primary cytomegalovirus (CMV) and a non-human primate model of Zika (ZIKV) infection. In the CMV cohort, a nested case control study was performed comparing pregnancies with and without fetal infection. Cases of fetal infection were further subdivided into those with and without adverse neurologic outcome. ZIKV samples were collected serially following maternal inoculation or saline. All ZIKV cases had histopathologic findings on necropsy. Serum was precipitated with ExoQuick solution and FCEs were isolated with biotinylated anti-Contactin-2/TAG1 antibody-streptavidin matrix immunoabsorption. FCE Synaptopodin (SYNPO) and Neurogranin (NG) protein levels were measured using standard ELISA kits and normalized to the exosome marker CD81.Results: Fetal CNSE SYNPO and NG were significantly reduced in cases of first trimester fetal CMV infection compared to those with infection limited to the mother but could not discriminate between fetal infection with and without adverse neurologic outcome. Following ZIKV inoculation, fetal CNSE SYNPO was reduced by 48 h and significantly reduced by day 4.Discussion: These data are the first to suggest that first trimester non-invasive diagnosis of fetal viral infection is possible. Fetal CNSEs have the potential to augment clinical and pre-clinical studies of perinatal viral infection. Serial sampling may be needed to discriminate between fetuses that are responding to treatment and/or recovering due to innate defenses and those that have ongoing neuronal injury. If confirmed, this technology may advance the paradigm of first trimester prenatal diagnosis and change the calculus for the cost benefit of CMV surveillance programs in pregnancy.

scholarly journals COT-04 Circulating biomarker for glioblastoma and primary central nervous system lymphoma -Next Generation Sequencing of small noncoding RNA-

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii21-ii21
Author(s):  
Shumpei Onishi ◽  
Fumiyuki Yamasaki ◽  
Motoki Takano ◽  
Ushio Yonezawa ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Noncoding Rna ◽  
Central Nervous System Lymphoma ◽  
Serum Samples ◽  
Small Noncoding Rna ◽  
Non Invasive ◽  
Diagnostic Models ◽  
Healthy Control ◽  
Generation Sequencing

Abstract Objective: Glioblastoma (GBM) and Primary Central Nervous System Lymphoma (PCNSL) are common intracranial malignant tumors. They sometimes present similar radiological findings and diagnoses could be difficult without surgical biopsy. For improving the current management, development of non-invasive biomarkers are desired. In this study, we explored the differently expressed circulating small noncoding RNA (sncRNA) in serum for specific diagnostic tool of GBM and PCNSL. Material & Methods: Serum samples were obtained from three groups: 1) GBM patients (N=26), 2) PCNSL patients (N=14) 3) healthy control (N=114). The total small RNAs were extracted from serum. The whole expression profiles of serum sncRNAs were measured using Next-Generation Sequencing System. We analyzed serum levels of sncRNAs (15–55 nt) in each serum samples. The difference of sncRNAs expression profile among three groups were compared. Data analysis was performed by logistic regression analysis followed by leave-one-out cross-validation (LOOCV). The accuracy of diagnostic models of sncRNAs combination were evaluated by receiver operating characteristic (ROC) analysis. Results: We created the combination models using three sncRNA in each models based on the logistic regression analysis. The model 1 (based on sncRNA-X1, X2 and X3) enabled to differentiate GBM patients form healthy control with a sensitivity of 92.3% and a specificity of 99.2% (AUC: 0.993). The model 2 (based on sncRNA-Y1, Y2 and Y3) enabled to differentiate PCNSL patients form healthy control with a sensitivity of 100% and a specificity of 93.9% (AUC: 0.984). The model 3 (based on sncRNA-Z1, Z2 and Z3) enabled to differentiate GBM patients form PCNSL patients with a sensitivity of 92.3% and a specificity of 78.6% (AUC: 0.920). Conclusion: We found three diagnostic models of serum sncRNAs as non-invasive biomarkers potentially useful for detection of GBM and PCNSL from healthy control, and for differentiation GBM from PCNSL.

scholarly journals Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 492
Author(s):  
Charlotte A. René ◽  
Robin J. Parks
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Significant Barrier ◽  
The Central Nervous System ◽  
Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

scholarly journals Central Nervous System Cell-Derived Exosomes in Neurodegenerative Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yang Tian ◽  
Chen Fu ◽  
Yifan Wu ◽  
Yao Lu ◽  
Xuemei Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Glia Cells ◽  
Central Nervous System Cell ◽  
The Central Nervous System ◽  
System Cell ◽  
Almost All

Exosomes are a type of extracellular vesicles secreted by almost all kinds of mammalian cells that shuttle “cargo” from one cell to another, indicative of its role in cell-to-cell transportation. Interestingly, exosomes are known to undergo alterations or serve as a pathway in multiple diseases, including neurodegenerative diseases. In the central nervous system (CNS), exosomes originating from neurons or glia cells contribute to or inhibit the progression of CNS-related diseases in special ways. In lieu of this, the current study investigated the effect of CNS cell-derived exosomes on different neurodegenerative diseases.

MENINGOENCEPHALITIS AND LABORATORY EVIDENCE OF TRIPLE INFECTION WITH CALIFORNIA ENCEPHALITIS VIRUS, ECHOVIRUS II, AND MUMPS

PEDIATRICS ◽  
1973 ◽  
Vol 51 (4) ◽  
pp. 680-684 ◽  
Author(s):  
Henry H. Balfour ◽  
Gregory L. Seifert ◽  
Milton H. Seifert ◽  
Paul G. Quie ◽  
Charlene K. Edelman ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Infection ◽  
Central Nervous System Disease ◽  
Encephalitis Virus ◽  
Laboratory Findings ◽  
Laboratory Evidence ◽  
System Disease ◽  
Triple Infection ◽  
Echovirus Type

This report emphasizes that in acute central nervous system disease, multiple viral agents may be implicated in the same patient. A 6-year-old girl with meningoencephalitis had laboratory evidence for simultaneous or closely spaced infections with California encephalitis virus, echovirus type 11, and mumps. Documentation of the finding of triple viral infection was based on at least two laboratory findings for each agent. The patient lived in an area where California encephalitis was prevalent.

Odor Perception

2012 ◽  
pp. 44-59 ◽  
Author(s):  
Mitsuo Tonoike
Keyword(s):  
Signal Transduction ◽  
Central Nervous System ◽  
Nervous System ◽  
Information Processing ◽  
Non Invasive ◽  
Olfactory Acuity ◽  
Central Regions ◽  
Olfactory Systems ◽  
The Central Nervous System ◽  
The Brain

Though olfaction is one of the necessary senses and indispensable for the maintenance of the life of the animal, the mechanism of olfaction had not yet been understood well compared with other sensory systems such as vision and audition. However, recently, the most basic principle of “signal transduction on the reception and transmission for the odor” has been clarified. Therefore, the important next problem is how the information of odors about is processed in the Central Nervous System (CNS) and how odor is perceived in the human brain. In this chapter, the basic olfactory systems in animal and human are described and examples such as “olfactory acuity, threshold, adaptation, and olfactory disorders” are discussed. The mechanism of olfactory information processing is described under the results obtained by using a few new non-invasive measuring methods. In addition, from a few recent studies, it is shown that olfactory neurophysiological information is passing through some deep central regions of the brain before finally being processed in the orbito-frontal areas.

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