scholarly journals Multiple Sclerosis: Microglia, Monocytes, and Macrophage-Mediated Demyelination

2021 ◽  
Author(s):  
John W Prineas ◽  
John D E Parratt
Keyword(s):  
Multiple Sclerosis ◽  
Cerebral Cortex ◽  
Gray Matter ◽  
Progressive Disease ◽  
Myeloid Cell ◽  
Cell Types ◽  
Demyelinating Diseases ◽  
Homogeneous Population ◽  
Mhc Ii ◽  
Large Numbers

Abstract This study examined the roles of microglia and monocytes in myelin destruction in patients with early multiple sclerosis (MS). Twenty-two cases were studied; the clinical duration was <9 weeks in 10 cases. Twenty myeloid cell subtypes or categories were identified including 2 cell types not known previously to occur in demyelinating diseases. Commencing myelin breakdown in plaques and in perivascular and subpial tissues occurred in the immediate presence of infiltrating monocytes and was effected by a homogeneous population of IgG-positive Fc receptor-bearing early phagocytes interacting with abnormal myelin. Oligodendrocyte apoptosis was observed in intact myelinated tissue bordering areas of active demyelination. Capillaries in the cerebral cortex plugged by large numbers of monocytes were common in acute cases of MS and in a patient with a neuromyelitis optica variant and extreme systemic recruitment of monocytes. In an MS patient with progressive disease, microglial nodules centered on MHC-II-positive capillaries plugged by monocytes were present in the cerebral cortex. This constitutes a new gray matter lesion in MS.

Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

2018 ◽  
pp. 172-185
Author(s):  
Hans Lassmann ◽  
Danielle Seilhean
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Gray Matter ◽  
Acute Disseminated Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Scar Formation ◽  
Demyelinating Diseases ◽  
Primary Demyelination ◽  
Similarities And Differences ◽  
Progressive Stage

This chapter describes the basic neuropathology of multiple sclerosis and other inflammatory demyelinating diseases. It specifically addresses the nature of multiple sclerosis lesions, characterized by inflammation, selective primary demyelination with partial preservation of axons, remyelination, and reactive astroglial scar formation. Attention is paid to the importance of demyelinated lesions in the gray matter, and it discusses the differences of the pathology between the relapsing and the progressive stage of the disease. Finally, it summarizes the similarities and differences between multiple sclerosis and other inflammatory demyelinating diseases, such as acute multiple sclerosis, Baló concentric sclerosis, neuromyelitis optica, myelin oligodendrocyte glycoprotein antibody-associated disease and acute disseminated encephalomyelitis.

Acute and chronic synaptic pathology in multiple sclerosis gray matter

2021 ◽  
pp. 135245852110221
Author(s):  
Marco Vercellino ◽  
Stella Marasciulo ◽  
Silvia Grifoni ◽  
Elena Vallino-Costassa ◽  
Chiara Bosa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Gray Matter ◽  
Axonal Loss ◽  
Strong Indication ◽  
Synaptic Loss ◽  
Synaptic Density ◽  
Synaptic Pathology ◽  
Gabaergic Synapses ◽  
And Control

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions. Over 1,000,000 individual synapses were identified and counted using confocal microscopy, and further characterized as glutamatergic/GABAergic. Synaptic counts were also correlated with neuronal/axonal loss. Results: Important synaptic loss was observed in active demyelinating GM lesions (−58.9%), while in chronic inactive GM lesions, synaptic density was only mildly reduced compared to adjacent non-lesional gray matter (NLGM) (−12.6%). Synaptic loss equally affected glutamatergic and GABAergic synapses. Diffuse synaptic loss was observed in MS NLGM compared to control GM (−21.2% overall). Conclusion: This study provides evidence, in MS brain tissue, of acute synaptic damage/loss during active GM inflammatory demyelination and of synaptic reorganization in chronically demyelinated GM, affecting equally glutamatergic and GABAergic synapses. Furthermore, this study provides a strong indication of widespread synaptic loss in MS NLGM also independently from focal GM demyelination.

scholarly journals Three distinct tolerogenic CD14+ myeloid cell types to actively manage autoimmune disease: Opportunities and challenges

2021 ◽  
Vol 120 ◽  
pp. 102645
Author(s):  
Glenn F. van Wigcheren ◽  
Daphne Roelofs ◽  
Carl G. Figdor ◽  
Georgina Flórez-Grau
Keyword(s):  
Autoimmune Disease ◽  
Myeloid Cell ◽  
Cell Types

scholarly journals Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies

2021 ◽  
Vol 22 (14) ◽  
pp. 7536
Author(s):  
Inez Wens ◽  
Ibo Janssens ◽  
Judith Derdelinckx ◽  
Megha Meena ◽  
Barbara Willekens ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Treatment Options ◽  
Cell Types ◽  
Peripheral Blood Mononuclear ◽  
Tailored Treatment ◽  
Key Issues ◽  
The Central Nervous System

Currently, there is still no cure for multiple sclerosis (MS), which is an autoimmune and neurodegenerative disease of the central nervous system. Treatment options predominantly consist of drugs that affect adaptive immunity and lead to a reduction of the inflammatory disease activity. A broad range of possible cell-based therapeutic options are being explored in the treatment of autoimmune diseases, including MS. This review aims to provide an overview of recent and future advances in the development of cell-based treatment options for the induction of tolerance in MS. Here, we will focus on haematopoietic stem cells, mesenchymal stromal cells, regulatory T cells and dendritic cells. We will also focus on less familiar cell types that are used in cell therapy, including B cells, natural killer cells and peripheral blood mononuclear cells. We will address key issues regarding the depicted therapies and highlight the major challenges that lie ahead to successfully reverse autoimmune diseases, such as MS, while minimising the side effects. Although cell-based therapies are well known and used in the treatment of several cancers, cell-based treatment options hold promise for the future treatment of autoimmune diseases in general, and MS in particular.

Mild gray matter atrophy in patients with long-standing multiple sclerosis and favorable clinical course

2021 ◽  
pp. 135245852110196
Author(s):  
Rosa Cortese ◽  
Marco Battaglini ◽  
Francesca Parodi ◽  
Maria Laura Stromillo ◽  
Emilio Portaccio ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Gray Matter ◽  
Clinical Course ◽  
Resonance Imaging ◽  
Volume Changes ◽  
Magnetic Resonance Imaging Mri ◽  
Global Brain ◽  
Diffuse Brain

The mechanisms responsible for the favorable clinical course in multiple sclerosis (MS) remain unclear. In this longitudinal study, we assessed whether magnetic resonance imaging (MRI)-based changes in focal and diffuse brain damage are associated with a long-term favorable MS diseases course. We found that global brain and gray matter (GM) atrophy changes were milder in MS patients with long-standing disease (⩾30 years from onset) and favorable (no/minimal disability) clinical course than in sex-age-matched disable MS patients, independently of lesions accumulation. Data showed that different trajectories of volume changes, as reflected by mild GM atrophy, may characterize patients with long-term favorable evolution.

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.

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