scholarly journals In Vivo Targeting of the Neurovascular Unit: Challenges and Advancements

2021 ◽  
Author(s):  
Oandy Naranjo ◽  
Olivia Osborne ◽  
Silvia Torices ◽  
Michal Toborek
Keyword(s):  
Multiple Sclerosis ◽  
Fluid Transport ◽  
Neurological Diseases ◽  
Neurovascular Unit ◽  
Protein Markers ◽  
Transport Studies ◽  
Selective Targeting ◽  
The Central Nervous System ◽  
Made In

AbstractThe blood–brain barrier (BBB) is essential for the homeostasis of the central nervous system (CNS). Functions of the BBB are performed by the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, basement membrane, and neurons. NVU cells interact closely and together are responsible for neurovascular coupling, BBB integrity, and transendothelial fluid transport. Studies have shown that NVU dysfunction is implicated in several acute and chronic neurological diseases, including Alzheimer’s disease, multiple sclerosis, and stroke. The mechanisms of NVU disruption remain poorly understood, partially due to difficulties in selective targeting of NVU cells. In this review, we discuss the relative merits of available protein markers and drivers of the NVU along with recent advancements that have been made in the field to increase efficiency and specificity of NVU research.

scholarly journals Ultra-high-field 7-T MRI in multiple sclerosis and other demyelinating diseases: from pathology to clinical practice

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolo’ Bruschi ◽  
Giacomo Boffa ◽  
Matilde Inglese
Keyword(s):  
Multiple Sclerosis ◽  
High Field ◽  
Neurological Diseases ◽  
Lesion Detection ◽  
Demyelinating Diseases ◽  
Metabolic Imaging ◽  
Central Vein ◽  
Ultra High Field ◽  
Functional Features

Abstract Magnetic resonance imaging (MRI) is essential for the early diagnosis of multiple sclerosis (MS), for investigating the disease pathophysiology, and for discriminating MS from other neurological diseases. Ultra-high-field strength (7-T) MRI provides a new tool for studying MS and other demyelinating diseases both in research and in clinical settings. We present an overview of 7-T MRI application in MS focusing on increased sensitivity and specificity for lesion detection and characterisation in the brain and spinal cord, central vein sign identification, and leptomeningeal enhancement detection. We also discuss the role of 7-T MRI in improving our understanding of MS pathophysiology with the aid of metabolic imaging. In addition, we present 7-T MRI applications in other demyelinating diseases. 7-T MRI allows better detection of the anatomical, pathological, and functional features of MS, thus improving our understanding of MS pathology in vivo. 7-T MRI also represents a potential tool for earlier and more accurate diagnosis.

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Current Methods of Magnetic Resonance for Noninvasive Assessment of Molecular Aspects of Pathoetiology in Multiple Sclerosis

2020 ◽  
Vol 21 (17) ◽  
pp. 6117
Author(s):  
Petra Hnilicová ◽  
Oliver Štrbák ◽  
Martin Kolisek ◽  
Egon Kurča ◽  
Kamil Zeleňák ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Neuronal Degeneration ◽  
Metabolic Stress ◽  
Pathological Process ◽  
Diagnostic Tools ◽  
Powerful Analytical Tool ◽  
The Central Nervous System ◽  
Molecular Aspects

Multiple sclerosis (MS) is an autoimmune disease with expanding axonal and neuronal degeneration in the central nervous system leading to motoric dysfunctions, psychical disability, and cognitive impairment during MS progression. The exact cascade of pathological processes (inflammation, demyelination, excitotoxicity, diffuse neuro-axonal degeneration, oxidative and metabolic stress, etc.) causing MS onset is still not fully understood, although several accompanying biomarkers are particularly suitable for the detection of early subclinical changes. Magnetic resonance (MR) methods are generally considered to be the most sensitive diagnostic tools. Their advantages include their noninvasive nature and their ability to image tissue in vivo. In particular, MR spectroscopy (proton 1H and phosphorus 31P MRS) is a powerful analytical tool for the detection and analysis of biomedically relevant metabolites, amino acids, and bioelements, and thus for providing information about neuro-axonal degradation, demyelination, reactive gliosis, mitochondrial and neurotransmitter failure, cellular energetic and membrane alternation, and the imbalance of magnesium homeostasis in specific tissues. Furthermore, the MR relaxometry-based detection of accumulated biogenic iron in the brain tissue is useful in disease evaluation. The early description and understanding of the developing pathological process might be critical for establishing clinically effective MS-modifying therapies.

Rituximab in patients with pediatric multiple sclerosis and other demyelinating disorders of the CNS: Practical considerations

2020 ◽  
pp. 135245852093279 ◽  
Author(s):  
Angelo Ghezzi ◽  
Brenda Banwell ◽  
Amit Bar-Or ◽  
Tanuja Chitnis ◽  
Russell C Dale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pediatric Patients ◽  
Neurological Diseases ◽  
Duration Of Treatment ◽  
Pediatric Multiple Sclerosis ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Anti Cd20 ◽  
Demyelinating Disorders

Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.

scholarly journals Cytomorphological and Cytochemical Identification of Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Subhajit Das Sarma ◽  
Koushik Chatterjee ◽  
Himadri Dinda ◽  
Dhriti Chatterjee ◽  
Jayasri Das Sarma
Keyword(s):  
Central Nervous System ◽  
Animal Model ◽  
Immune Cells ◽  
Microglial Activation ◽  
Neurological Diseases ◽  
Neuronal Dysfunction ◽  
Ultrastructural Studies ◽  
The Central Nervous System ◽  
Made In

Microglia is one of the major resident immune cells in the central nervous system and is considered to be the key cellular mediator of neuroinflammatory processes. Identification of different Microglial states of activation by morphologic means has been one of the major challenges in the field of neurobiology of diseases. Therefore, microglial biology demands techniques to identify differing stages of microglia in different neuroanatomic locations as well as understanding the role of Microglia in different Neurological diseases. This present study is aimed towards summarizing the literature and for understanding the progress made in different Cytomorphological and Cytochemical techniques of identifying Microglia. This study also review recently used Immunohistochemistry techniques, along with Ultrastructural studies determining different morphological features of resting to activated phagocytic Microglia in a viral induced experimental animal model of neuroinflammation. Results revealed that chronic Microglial activation is considered to be an important component of neuronal dysfunction, injury, and loss (and hence to disease progression). Thus, Microglial research with special emphasis on identification of different activation states of Microglia has gradually become significant.

Relapsing-Remitting Multiple Sclerosis - Current Treatment Options and Perspectives for the Future

2010 ◽  
Vol 5 (1) ◽  
pp. 78
Author(s):  
Alex Rae-Grant ◽  
Daniel Ontaneda ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Current Treatment ◽  
Relapsing Remitting ◽  
Significant Disability ◽  
The Central Nervous System ◽  
Disease Modifying Agents ◽  
Phase Ii And Iii ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Made In

Multiple sclerosis (MS) is the most prevalent demyelinating condition of the central nervous system and produces significant disability over time. For many years it was considered to be an untreatable disease, but great advances have been made in the treatment of MS in the last 20 years. There are currently six US Food and Drug Administration (FDA)-approved disease-modifying agents for the relapsing form of the disease. We review in detail these medications and the pivotal trials leading to their approval. We will briefly review non-FDA-approved medications already used in MS. We will also discuss some of the medications currently being studied in phase II and III trials that are not yet approved for use in MS.

Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression

2001 ◽  
Vol 7 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Yu-Min Huang ◽  
Mathilde Kouwenhoven ◽  
Ya-Ping Jin ◽  
Rayomand Press ◽  
Wen-Xin Huang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Neurological Diseases ◽  
Interleukin 4 ◽  
Gm Csf ◽  
The Central Nervous System ◽  
Macrophage Colony ◽  
Antigen Presenting

Dendritic cells (DC) are important antigen presenting cells (APC) and play a major role in initiating and orchestrating immune responses by priming T cells. Little is known about involvement of DC in multiple sclerosis (MS), where auto-aggressive T cells against myelin autoantigens are considered to contribute to inflammation and demyelination in the central nervous system. In this study, we compared phenotype and cytokine secretion of DC from patients with MS, other neurological diseases (OND) and healthy subjects. DC were generated from blood adherent mononuclear cells (MNC) by culture for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield and morphology of DC were similar in MS patients and controls. In both, the DC phenotype was that of immature myeloid lineage, comprising CD1a+ and CD11c+. The proportion of CD1a+ DC, being important for presentation of lipid antigens to T cells, was higher in MS patients compared to controls. The proportion of CD86+ DC, a co-stimulatory molecule that is assumed to promote Th2 differentiation, was low in MS. Low proportions of CD86+ DC were only observed in untreated MS patients but not in patients treated with IFN-b. Production of IL-10 and IL-12 p40 by DC did not differ in MS patients and controls. These findings indicate that alterations of functionally important surface molecules on DC are associated with MS.

IFN-β treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing -remitting multiple sclerosis

2004 ◽  
Vol 10 (6) ◽  
pp. 630-635 ◽  
Author(s):  
C Espejo ◽  
L Brieva ◽  
G Ruggiero ◽  
J Río ◽  
X Montalban ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chronic Inflammatory Disease ◽  
Autoimmune Response ◽  
T Cell Proliferation ◽  
Immunomodulatory Effects ◽  
Cd25 Expression ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system probably mediated by Th1 lymphocytes. IFN-b is an established therapy for relapsing MS patients, although the mechanisms underlying its efficacy are yet to be well characterized. We determined IL-2 production, CD25 expression and T-cell proliferation from relapsing -remitting MS patients before and three months after starting therapy. A decrease in the percentage of CD80-induced IL-2-producing cells was observed after in vivo IFN-b treatment. These data support that one of the immunomodulatory effects of IFN-b treatment in MS may be a limitation of the autoimmune response modifying the CD80:CD28/CTLA-4 pathway.

scholarly journals Effects of multiple sclerosis in pregnant and post-birth: particularities of the disease activity

2021 ◽  
Author(s):  
Bianca Barbosa Araldi ◽  
Victor Hugo Gomes ◽  
Bruno Ludvig Vieira ◽  
Klesia Adayani Rodrigues ◽  
Andressa Gabrieli da Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Cumulative Effect ◽  
Demyelinating Diseases ◽  
Hormonal Changes ◽  
Neuroprotective Effects ◽  
Maternal Immune System ◽  
The Central Nervous System

Introduction: Demyelinating diseases are a heterogeneous group of neurological diseases related to autoimmunity whose representative is Multiple Sclerosis (MS). It is characterized by an immune-mediated demyelination of the central nervous system, with a typical outbreak and remission clinic. During pregnancy, a reduction in disease activity was noted due to immunomodulatory effects, and an increase in outbreaks in the puerperium. Thus, our goal is to demonstrate the relationship between pregnancy and MS. Methods: This is a systematic bibliographic review based on searching the SCIELO, PUBMED and UPTODATE databases using the words “Multiple Sclerosis”, “Pregnancy”, “Demyelinating diseases” and “Neurological Disorders”. Discussion: Pregnancy is responsible for numerous changes in the maternal body resulting from hormonal changes with an immunological and neuroprotective effect. Until the beginning of the 20th century, it was considered a risk factor or precipitator of outbreaks in these patients. In 1950, Tillmann et al. questioned him and concluded that pregnancy reduces the risk of outbreaks of the disease and that relapses were more associated with postpartum. The question is still raised by several authors, due to their interest in the search for intricate protective factors in the genesis and cure of the disease. It is believed that immunological changes in pregnancy tend to suppress the maternal immune system preventing fetal rejection, and together with gestational hormones, they are able to make neuronal tissue more resistant to inflammatory aggression and greater capacity for cell repair. In the puerperium, there was an increase in outbreaks of the disease, probably associated with a reduction in hormone levels, the effects of which are lost after the elimination of the fetus. Breastfeeding is not associated with the prevention or risk of new MS outbreaks. The frequency of outbreaks before conception is the only independent predictor of new post-term episodes. There is no consensus regarding the therapeutic approach in these pregnant women. Conclusion: Evidence supports the association between pregnancy, reduced activity of MS and increased activity in the 3 months postpartum, due to the probable loss of neuroprotective effects associated with hormones. Recommendations regarding the use of immunomodulator are suspended before conception (“washout”) until term. New evidence did not associate the use of interferon-β with abortion, cesarean section or low birth weight. There was a benefit of long-term parity with a cumulative effect on the patient’s immunohumor modulation.

scholarly journals Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1899
Author(s):  
Moritz Förster ◽  
Christopher Nelke ◽  
Saskia Räuber ◽  
Hans Lassmann ◽  
Tobias Ruck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Nitrosative Stress ◽  
Neurological Diseases ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Unknown Etiology ◽  
Immune Mediated ◽  
Pubmed Database ◽  
The Central Nervous System ◽  
Nitrite Nitrate

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis.

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