Morphological changes in oligodendrocytes in the intact mouse optic nerve following intravitreal injection of tumour necrosis factor

Butt, Arthur M.; Jenkins, Huw G.

doi:10.1016/0165-5728(94)90125-2

Cited by 55 publications

(30 citation statements)

References 19 publications

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“…Destruction of oligodendrocytes or myelin leads to disastrous consequences for optic nerve function, and underlies the optic neuritis that is often an early stage of the pathology of the human demyelinating disease, multiple sclerosis (MS). [14][15][16][17] Studies in animal models of MS have demonstrated that optic nerve oligodendrocytes are markedly affected during demyelination in experimental autoimmune encephalomyelitis (EAE), 14 viral induced demyelination, 15 and following treatment with tumour necrosis factor-a (TNF-a), a cytokine implicated in MS ( Figure 2). 16 Demyelination is marked by the attenuation of and, in extreme cases, complete loss of internodal myelin sheaths in individual oligodendrocytes ( Figure 2g-i).…”

Section: Oligodendrocytes and Axoglial Interactionsmentioning

confidence: 99%

“…[14][15][16][17] Studies in animal models of MS have demonstrated that optic nerve oligodendrocytes are markedly affected during demyelination in experimental autoimmune encephalomyelitis (EAE), 14 viral induced demyelination, 15 and following treatment with tumour necrosis factor-a (TNF-a), a cytokine implicated in MS ( Figure 2). 16 Demyelination is marked by the attenuation of and, in extreme cases, complete loss of internodal myelin sheaths in individual oligodendrocytes ( Figure 2g-i). This results in focal demyelination and the slowed conduction velocities and conduction block characteristic of EAE and MS. 14,17 Remyelination and recovery of axonal function occur during remission in EAE and MS, 14 and this is a function of newly differentiated cells formed from the adult OPC pool.…”

Section: Oligodendrocytes and Axoglial Interactionsmentioning

confidence: 99%

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Functions of optic nerve glia: axoglial signalling in physiology and pathology

Butt

Pugh

Hubbard

et al. 2004

Eye

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An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

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Section: Oligodendrocytes and Axoglial Interactionsmentioning

confidence: 99%

Section: Oligodendrocytes and Axoglial Interactionsmentioning

confidence: 99%

Functions of optic nerve glia: axoglial signalling in physiology and pathology

Butt

Pugh

Hubbard

et al. 2004

Eye

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“…The role of TNFα in CNS disease is paradoxical, with reported protective and pathologic roles. In rodents, TNFα is mostly damaging to the CNS with deleterious effects reported on astrocytes, oligodendrocytes, myelin, and axons [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89]. In MS patients, neutralization of TNFα with a specific monoclonal antibody or a soluble TNFα receptor exacerbated clinical symptoms, suggesting in humans this cytokine is likely protective [90,91].…”

Section: Discussionmentioning

confidence: 99%

B Cell Receptor Recognition of Glatiramer Acetate is Required for Efficacy through Antigen Presentation and Cytokine Production

Jackson

Selva²,

Niedzielko³

et al. 2014

J Clin Cell Immunol

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Multiple Sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) leading to neuronal demyelination, lack of remyelination, and axonal loss. If left untreated, patients inevitably suffer from severe cognitive, psychological and physical disabilities.Although not yet approved, B cell depletion achieved with anti-CD20 monoclonal antibodies is the most effective therapy to-date in MS patients. As this therapeutic depletes immune cells potentially important in pathogen immunity, an immense need remains for highly efficacious therapeutics maintaining a favorable safety profile. Even amongst the emergence of new therapeutic options for patients with MS, the myelin basic protein mimetic, Copaxone (glatiramer acetate, GA), remains the most commonly prescribed drug in the United States. As specific B cell depletion appears to be the most effective therapy for MS patients, the goal of this study was to further elucidate the mechanism of action of GA on B lymphocytes. Our studies show that GA directly interacts with human and murine B cell receptors (BCR) inducing the activation of B lymphocytes and BCR recognition of GA is required for efficacy in an animal model of MS. GA loaded B lymphocytes resulted in IL-2 production from CD4 + T cells suggesting B lymphocytes serve as an antigen presentation source for GA. In fifty-percent of the MS patients tested, GA stimulation reduced baseline levels of the pro-inflammatory cytokines IL-6 and TNFα in purified B lymphocytes, while other cytokines were not consistently altered. Taken together, this data suggests that the mechanism of action of GA on B lymphocytes includes the presentation of GA to T lymphocytes in the context of an anti-inflammatory cytokine milieu. The results from this study provide a strong foundation for future exploration of optimal Copaxone responders or synergistic combination therapies with an improved risk: benefit ratio compared to currently approved therapeutics for MS.

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“…Aus diesem Grund wird TNF-α als ein wich- Raine, 1988;Selmaj et al, 1991;Jenkins and Ikeda 1992;Louis et al, 1993;Mc Larnon et al, 1993;Butt and Jenkins 1994;D'Souza et al, 1995;Soliven and Szuchet 1995;Hisahara et al, 1997].…”

Section: Rolle Des Tnf-α Für Myelin Und Oligodendrocytenunclassified