Mechanisms of Disease Pathogenesis in Multiple Sclerosis / Francisco Javier Quintana, editors.

Format:

Book

Contributor:

Quintana, Francisco Javier, editor.

Language:

English

Subjects (All):

Multiple sclerosis.

Physical Description:

1 online resource (406 pages)

Edition:

First edition.

Place of Publication:

London, England : Academic Press, [2024]

Summary:

This comprehensive volume, edited by Francisco J. Quintana, delves into the mechanisms underlying the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. The book covers various aspects of MS, including clinical courses, diagnostic criteria, and unmet clinical needs. It explores novel imaging approaches and the role of infections, T cells, B cells, microglia, monocytes, and astrocytes in MS pathogenesis. Key topics include the impact of the microbiome, early high-efficacy treatments, and advancements in imaging techniques like MRI and PET scans. The book is intended for medical researchers, neurologists, and healthcare professionals seeking a deeper understanding of MS pathogenesis and potential therapeutic directions. Generated by AI.

Contents:

Front Cover

Mechanisms of Disease Pathogenesis in Multiple Sclerosis

Copyright

Contents

Contributors

1 - Multiple sclerosis: Clinical course, open questions, unmet clinical needs

Introduction

Clinical course

Disease stage and diagnostic criteria

Pathology &amp

relationship to MS stage

Open questions

What is the optimal strategy to manage newly diagnosed relapsing MS? Is there benign MS?

The role of early high-efficacy treatment

When can MS treatment safely be stopped?

How can blood biomarkers be used to improve disease monitoring?

How might recent MRI advances improve disease monitoring?

Central vein sign

Cortical lesions

Paramagnetic rim lesions and slowly expanding lesions

Leptomeningeal enhancement

Is there a role for disease monitoring by PET imaging?

How is the microbiome related to MS?

Unmet clinical needs

A cure for MS

Phase 3 trials in PPMS and SPMS

Remyelination

EBV and the potential for MS prevention

References

2 - Novel imaging approaches in multiple sclerosis

Use of MRI in pwMS

MRI as a diagnostic tool

Monitoring treatment effectiveness and response

MRI for drug safety monitoring

Novel imaging techniques

Paramagnetic rim lesions

Subpial demyelination

Spinal cord imaging

PET radiotracers

Blood-brain barrier permeability

Resting state

Other quantitative MRI methods

T1 relaxometry

T2 relaxometry, myelin water fraction, and magnetization transfer imaging

Diffusion microstructure

Diffusion MRI in multiple sclerosis

Quantitative susceptibility mapping

Perfusion imaging

Artificial intelligence in MS

Overview of AI models.

AI to measure and monitor brain and spinal cord atrophy

The importance of normative databases

AI to assist in lesion quantification and monitoring

AI to rule out differential diagnosis

Concluding remarks

3 - Effect of infections on multiple sclerosis

Infectious triggers linked to MS

Viral triggers

Epstein-Barr virus

Human Herpesvirus 6 (HHV-6)

Human endogenous retroviruses (HERV)

Coronavirus

Bacterial triggers

Helicobacter pylori

Chlamydia pneumoniae

Mechanisms by which host infections can lead to multiple sclerosis

Risk of relapse during systemic infection

Systemic mechanisms underlying T-cell activation in response to infection

Cellular and molecular mechanisms involved in MS relapses occurring during infections

The protective role of helminth infections against MS

The hygiene hypothesis

Evidence from animal models

Natural exposure of MS patients to helminth infections

Molecular mechanisms involved in helminth infection protection

4 - T cells in multiple sclerosis

Introduction: Why is multiple sclerosis a T cell mediated disease?

Concepts of T cell mediated inflammatory lesion induction in MS

Autoreactive T cell priming in lymph nodes draining peripheral sites

Autoreactive T cell priming in lymph nodes draining the CNS

Reactivation of T cells upon entry into the CNS compartment

Regulatory T cells in CNS inflammation

T cells in the systemic compartment of MS patients

T cells in the CSF and the meningeal compartments

T cells in the CNS parenchyma

Tissue imprinting of T cells

When systemic T cells might not be the major drivers of MS pathology any more

Perspective

Acknowledgments

5 - B cells in multiple sclerosis

B cell biology in homeostasis and inflammation.

Early B cell development

B cell development and activation in the periphery

B cell homeostasis - The BAFF/APRIL axis

BAFF and APRIL ligands

Expression and function of BAFF/APRIL receptors

Evidence for B cell involvement in multiple sclerosis

Oligoclonal antibody bands

Anti-MOG antibodies and MS

Anti-viral antibodies and MS

Prognostic value of CSF OCB

CNS-resident B cells

Histopathological evidence for B cells in the MS-resident CNS

B cell targeting therapies

Anti-CD20 monoclonal antibodies

Atacicept

Burton tyrosine kinase (BTK) inhibitors

B cells in experimental autoimmune encephalomyelitis (EAE)

Role of B cells in inducible models of EAE in C57Bl/6 mice

Myelin peptide immunization

Myelin protein immunization

Role of B cells in spontaneous models of EAE in C57Bl/6 mice

C57Bl/6 TCR and BCR transgenic mice

SJL/J TCR and BCR transgenic mice

Spontaneous EAE in the absence of checkpoint inhibitors

Role of B cells in EAE characterized by leptomeningeal inflammation in the brain

SJL/J EAE

Biozzi EAE

Antibody-independent functions of B cells in MS/EAE

Pathogenic B cells in MS/EAE

Antigen presentation

Dysregulated cytokine production

Regulatory B cells in MS/EAE

Memory B cell derived Breg (B10 cells)

Immature B cell derived Breg

Antibody secreting cells

IgA-producing B cells

Therapeutic directions targeting B cells in MS

Selective depletion of pathogenic B cells

Dismantling B cell rich leptomeningeal TLT

Augmenting regulatory B cell subsets

6 - Microglia in multiple sclerosis

CNS resident myeloid cells during homeostasis

Microglia

CNS-associated macrophages (CAM)

CNS-resident myeloid cells during neuroinflammation

Microglia in MS

Microglial phagocytosis and synapse loss during neuroinflammation.

Support of remyelination by microglia

Microglia and inflammation

CAM in MS

Myeloid cells MS

Outlook

7 - Monocytes in multiple sclerosis

Monocytes

Ontogeny

Steady-state

Inflammation

Multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE)

The duelists: Microglia vs monocytes

Pathogenesis of monocyte-derived cells in multiple sclerosis

Monocytes as antigen presenting cells

Infiltration of monocytes into the CNS parenchyma

Contribution of monocytes to tissue damage

Current therapies, current and past trials

8 - Antigen presenting cells in multiple sclerosis

Antigen processing and presentation on major histocompatibility complexes

Peripheral activation of autoreactive T cells

T-cell reactivation in the central nervous system

Anatomic location of neuroimmune interactions at CNS border regions

The dura mater

The leptomeninges

The choroid plexus

Possible cells functioning as APCs in the CNS

Border-associated macrophages

Dendritic cells

9 - Oligodendrocytes in multiple sclerosis

Basic properties of OLs/myelin

Structural properties

Metabolic properties of OLs

Heterogeneity of OLs

Regional distribution

Age related heterogeneity

Species differences

Histopathology of OLs/myelin in MS

Basis of OL injury

Acute cytotoxicity

Sublethal OL injury

Delayed lethal injury of OLs

Passive or accidental cell death (necrosis)

Regulated cell death (RCD)

Apoptosis

Necroptosis

Ferroptosis

Parthanatosis

Pyroptosis ("fiery death")

Autophagy-dependent cell death (ADCD)/Autosis

Sources of OL injury

Comparison of OPC versus mature OL direct injury

Response to inflammatory mediators

Response to metabolic stress.

Myelin injury and repair

Translational challenges

10 - Astrocytes in multiple sclerosis

Homeostatic astrocytes

Reactive astrocytes

Astrocytes in multiple sclerosis

Astrocytes in Parkinson's disease

Conclusions and future directions

11 - The blood-brain barrier in multiple sclerosis

Short introduction - the importance of the blood-brain barrier in multiple sclerosis and addressed topics

The BBB as part of the neurovascular unit, its entities and function

The brain endothelial cells actively shape the CNS environment during neuroinflammation

The role of AJs in the BEC barrier function

The role of TJs in the BEC barrier function

Failure of BEC barrier function in MS

BEC-associated cell adhesion molecules

BEC barrier function maintains an ideal milieu for neuronal activity

The role of cholesterol metabolism and lipid rafts in BEC barrier function

BECs and the neurovascular unit

The role of pericytes at the BBB in MS

The role of astrocytes at the BBB in MS

The role of the basement membrane at the BBB in MS

Early disturbance of the barrier function and endothelial transmigration of immune cells across the BBB in MS

Leukocyte attraction, infiltration, and interaction with the BBB

Target molecules for therapeutic approaches to interfere with leukocyte infiltration in MS

The role of cytokines in the activation of the brain endothelium and leukocyte infiltration

Dysfunctional neurovascular coupling linked to gray matter atrophy in MS patients

The general concept of neurovascular coupling

Neurovascular uncoupling and association with gray matter atrophy in MS

Possible factors for neurovascular uncoupling in MS

Angiodynamic changes and hypoxia-based treatment options in MS

12 - Microbiome in multiple sclerosis.

Introduction.

Notes:

Description based on publisher supplied metadata and other sources.

Part of the metadata in this record was created by AI, based on the text of the resource.

Description based on print version record.

Includes bibliographical references and index.

Other Format:

Print version: Quintana, Francisco Javier Mechanisms of Disease Pathogenesis in Multiple Sclerosis

ISBN:

9780128238493

OCLC:

1439596047