Astrocyte Involvement in the Acquired Demyelinating Diseases (original) (raw)
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Clinical and Experimental Neuroimmunology, 2012
Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis (MS) has long been debated, but NMO has been classified as a demyelinating disease. Since the discovery of an NMO-specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on end-feet of astrocytes, the clinical, magnetic resonance imaging and laboratory findings to distinguish NMO from MS have been clarified. Furthermore, pathological studies showed an extensive loss of immunoreactivities to astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), and perivascular deposition of immunoglobulins and activated complements with a relative preservation of the staining of myelin basic protein (MBP) in acute NMO lesions, but not in MS. In support of these pathological findings, the GFAP levels in the cerebrospinal fluid (CSF) during acute exacerbation of NMO are remarkably elevated compared with MBP and neurofilament, whereas the CSF-GFAP in MS is not different from those in controls. Additionally, recent experimental studies have convincingly shown that AQP4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that damage of astrocytes is far more severe than those of myelin and neurons, and that autoimmune astrocytopathy is the primary pathology in NMO. Based on these accumulated data, we propose that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease. (Clin. Exp. Neuroimmunol.
Multiple sclerosis. Current etiological concepts
California Medicine, 1972
An animal model for acute multiple sclerosis (MSa) is experimental allergic encephalomyelitis (EAE). EAE is produced by intradermal injection of a protein component of central nervous system (CNS) myelin. Ultrastructural studies of EAE and of a peripheral nerve analog, experimental allergic neuritis (EAN), have revealed an orderly sequence of cellular events leading to the destruction and removal of myelin with sparing of axons (primary demyelination). Acute MS has not been studied electron microscopically, but the ultrastructural similarities between EAN and a case of acute Landry-Guillain-Barre syndrome, a primary demyelinating disease of the peripheral nervous system, suggest that a similar sequence of events might be found in acute MS. While the pathological findings support a cellmediated or delayed hypersensitivity response, there is also evidence for the pathogenetic role of circulating antibodies. Among such evidence is included the finding that sera from animals with EAE and humans with acute MS rapidly produce a reversible block of complex (polysynaptic) electrical activity when applied to CNS tissue cultures, which suggests a possible mechanism for transient symptoms in Ms. Epidemiological and other studies link MS with a viral cause, although no direct evidence that MS is caused by a virus exists. Viral and immunological mechanisrs are not mutually exclusive in considering pathogenetic possibilities for MS, for it can be postulated that a viral infection of the central nervous system acts as a triggering agent for a series of immune responses, including production of a bioelectric blocking antibody and demyelination mediated by sensitized cells, the combination of which ultimately produces the total clinical picture of MS.
Expert Review of Neurotherapeutics, 2011
The spectrum of idiopathic inflammatory-demyelinating disorders of the CNS is classified based on clinical symptoms and signs, clinical severity, lesion distribution, neuroimaging features and cerebrospinal fluid characteristics. There is a wide variety of conditions in this broad spectrum. In some cases, the dissemination in the CNS is limited to the optic nerves and spinal cord. Neuromyelitis optica (NMO) and the NMO spectrum disorders have a predilection for the optic nerves and spinal cord. Clinical, MRI, cerebrospinal fluid and neuropathological features show that NMO could be considered as a distinct disease rather than as a variant of multiple sclerosis. Accurate and early diagnosis is critical to facilitate initiation of immunosuppressive and/or immunomodulatory therapy to prevent attacks and disability progression.
Multiple Sclerosis: Basic Concepts and Hypothesis
Mayo Clinic Proceedings, 1989
Multiple sclerosis, an inflammatory disease of the central nervous system, is characterized by primary destruction of myelin. This review covers recent advances in neuropathology, immunogenetics, neuroimmunology, and neurovirology that have provided insights regard ing its pathogenesis. Three hypotheses are discussed: (1) autoimmunity, (2) "bystander" demyelination, and (3) immune destruction of persistently infected oligodendrocytes. A paradigm for induction of primary demyelination is proposed in which immune cells recognize "foreign" antigens on the surface of oligodendrocytes in the context of major histocompatibility complex gene products. The final result of this scheme may be "dying-back gliopathy," the alteration being noted first in the most distal extension of the oligodendrocyte-that is, the myelin sheaths. PATHOLOGY Multiple sclerosis (MS) affects scattered areas of the central nervous system with a predilection for periventricular white matter, brainstem, spinal cord, and optic nerves. 1 The plaques are characterized by primary demyelination (destruction of myelin sheaths with preservation of axons) and death of oligodendro cytes (myelin-producing cells) within the center of the lesion. During the early evolution of the plaque, perivascular inflammatory cells (lymphocytes, plasma cells, macrophages) invade the substance of the white matter and are thought to play a critical role in myelin destruction. 2 This process is followed by extensive
Multiple sclerosis: a unique immunopathological syndrome of the central nervous system
Springer Seminars in Immunopathology, 1995
Multiple sclerosis (MS) is the most common, disabling neurological syndrome of young adults. The etiology is idiopathic, yet most authorities agree that the immune system is crucial in the pathogenesis of the recurrent and chronic injury to the central nervous system (CNS). Nearly identical histopathological findings occur in MS and related clinical syndromes, designated as "demyelinating diseases." Clinical presentation differentiates MS from the monophasic syndromes (optic neuritis, acute transverse myelitis, and Marburg disease) and the less-common relapsing syndromes (Devic's disease, Balo's concentric sclerosis). A chronic progressive variant of MS is also well recognized.