scholarly journals Multiple Sclerosis: Focus on Extracellular and Artificial Vesicles, Nanoparticles as Potential Therapeutic Approaches

2021 ◽  
Vol 22 (16) ◽  
pp. 8866
Author(s):  
Domenico Nuzzo ◽  
Pasquale Picone
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Mechanisms Of Action ◽  
Brain Barrier ◽  
Therapeutic Approaches ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Ms Therapy

Multiple sclerosis (MS) is an autoimmune disease of the Central Nervous System, characterized by an inflammatory process leading to the destruction of myelin with neuronal death and neurodegeneration. In MS, lymphocytes cross the blood-brain barrier, creating inflammatory demyelinated plaques located primarily in the white matter. MS potential treatments involve various mechanisms of action on immune cells, immunosuppression, inhibition of the passage through the blood-brain barrier, and immunotolerance. Bio-nanotechnology represents a promising approach to improve the treatment of autoimmune diseases by its ability to affect the immune responses. The use of nanotechnology has been actively investigated for the development of new MS therapies. In this review, we summarize the results of the studies on natural and artificial vesicles and nanoparticles, and take a look to the future clinical perspectives for their application in the MS therapy.

scholarly journals The blood–brain barrier in health and disease: Important unanswered questions

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Caterina P. Profaci ◽  
Roeben N. Munji ◽  
Robert S. Pulido ◽  
Richard Daneman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Neurological Conditions

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.

scholarly journals Role of the Extracellular Traps in Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyan Wu ◽  
Hanhai Zeng ◽  
Lingxin Cai ◽  
Gao Chen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Brain Barrier ◽  
Extracellular Traps ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Extracellular Trap

It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.

scholarly journals Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

2021 ◽  
Vol 22 (16) ◽  
pp. 8370
Author(s):  
Rodica Balasa ◽  
Laura Barcutean ◽  
Oana Mosora ◽  
Doina Manu
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Neuroprotective Effect ◽  
Combined Therapy ◽  
Neurovascular Unit ◽  
Dimethyl Fumarate ◽  
Mechanisms Of Action ◽  
Brain Barrier ◽  
Neurodegenerative Process ◽  
Blood Brain

The disruption of blood–brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained ‘inside-out’ demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB’s endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS. Hypoxia in MS might be produced per se by the NVU malfunction or secondary to mitochondria dysfunction. We present three different but related terms that denominate the ongoing neurodegenerative process in progressive forms of MS that are indirectly related to BBB disruption: progression independent of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effective in treating MS. Detailed mechanisms of action of these DMTs are described and also illustrated in dedicated images. With increasing knowledge about the involvement of BBB in MS pathology, BBB might become a therapeutic target in MS not only to make it impenetrable against activated immune cells but also to allow molecules that have a neuroprotective effect in reaching the cell target inside the CNS.

scholarly journals Immunologic Privilege in the Central Nervous System and the Blood–Brain Barrier

2012 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Leslie L Muldoon ◽  
Jorge I Alvarez ◽  
David J Begley ◽  
Ruben J Boado ◽  
Gregory J del Zoppo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Complex Structure ◽  
Neurovascular Unit ◽  
Brain Barrier ◽  
Immune Mediators ◽  
Blood Brain ◽  
The Central Nervous System

The brain is in many ways an immunologically and pharmacologically privileged site. The blood–brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.

scholarly journals Biomarkers Indicative of Blood-Brain Barrier Disruption in Multiple Sclerosis

2006 ◽  
Vol 22 (4) ◽  
pp. 235-244 ◽  
Author(s):  
Emmanuelle Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Mri ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Cytokines And Chemokines ◽  
Blood Brain ◽  
Mri Scans ◽  
The Central Nervous System ◽  
Brain Barrier Disruption

Blood-brain barrier (BBB) disruption is one of the hallmarks of multiple sclerosis (MS). It is incompletely understood whether BBB disruption is the initial MS event leading to MS lesion formation or whether it is merely a consequence of cellular infiltration in the central nervous system (CNS). The presence of gadolinium enhancing (Gd+) lesions on serial brain MRI scans is frequently used to evaluate BBB disruption. The presence of Gd enhancement has therefore been used as a reference for most works evaluating promising biomarkers of BBB disruption that are reviewed here. These promising biomarkers include cytokines and chemokines, and their receptors, cell surface markers, and matrix metalloproteinases and their natural inhibitors. At this time, none of these markers have been shown as sensitive as the presence of Gd enhancement to reflect BBB disruption. However, MRI scanning is not only unpractical and expensive; it may also under represent the overall extent of BBB disruption. Developing new MS biomarkers that are sensitive and specific for BBB disruption could 1) improve the monitoring of disease activity; 2) improve the monitoring of response to MS therapies which target BBB disruption; and 3) advance our understanding of dynamic MS processes participating in BBB disruption.

scholarly journals How do immune cells overcome the blood-brain barrier in multiple sclerosis?

FEBS Letters ◽  
2011 ◽  
Vol 585 (23) ◽  
pp. 3770-3780 ◽  
Author(s):  
Catherine Larochelle ◽  
Jorge Ivan Alvarez ◽  
Alexandre Prat
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals miRNAs Participate in MS Pathological Processes and Its Therapeutic Response

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Wu ◽  
Guangjie Chen
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Therapeutic Response ◽  
Response To Therapy ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
Cns Lesions

Multiple sclerosis is the most common autoimmune disease of the central nervous system. It is believed that the increased migration of autoreactive lymphocytes across the blood-brain barrier (BBB) may be responsible for axonal demyelination of neurons. In this review, we discuss microRNAs participating in the pathological processes of MS, including periphery inflammation, blood-brain barrier disruption, and CNS lesions, and in its therapeutic response, in order to find biomarkers of disease severity and to predict the response to therapy of the diseases.

scholarly journals Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1294
Author(s):  
Yogesh R. Suryawanshi ◽  
Autumn J. Schulze
Keyword(s):  
Immune Responses ◽  
Malignant Glioma ◽  
Blood Brain Barrier ◽  
Tumor Heterogeneity ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Brain Barrier ◽  
Current Status ◽  
Blood Brain ◽  
Federal Authority

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood–brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood–brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

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