title: The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis.
abstract: Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one's genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis.
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Wellcome Trust-MRC Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY, UK.|Department of Brain and Behavioural Sciences, National Neurological Institute C. Mondino, University of Pavia, 27100 Pavia, Italy.
authors: Giulia
authors: G
authors: Mallucci
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Wellcome Trust-MRC Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY, UK.
authors: Luca
authors: L
authors: Peruzzotti-Jametti
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Wellcome Trust-MRC Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY, UK.|National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bldg10/Rm5B06, MSC 1401, 10 Center Drive, Bethesda, MD 20892, USA.
authors: Joshua D
authors: JD
authors: Bernstock
authors: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Wellcome Trust-MRC Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY, UK.
authors: Stefano
authors: S
authors: Pluchino
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology*; D066128:Gray Matter / Q000276:immunology / Q000473:pathology*; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009457:Neuroglia / Q000276:immunology / Q000473:pathology*; D015213:Neuroimmunomodulation / Q000502:physiology; D009474:Neurons / Q000276:immunology / Q000473:pathology*
keywords: Demyelination; Immune modulation; Inflammation; Multiple sclerosis; Neuroimmunology; Regeneration