Studies in Multiple Sclerosis

Putnam, Tracy J.

doi:10.1001/archneurpsyc.1936.02260060131011

Cited by 65 publications

(7 citation statements)

References 19 publications

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“…This process, in contrast to acute axonal injury in active lesions, may be continued for prolonged time periods and may explain the observed profound reduction of axonal density in established MS plaques. 20,52,53 Finally, our results show that axonal pathology in inflammatory demyelinating lesions of chronic MOG-induced autoimmune encephalomyelitis closely reflects that found in MS. This particular model of MOGinduced EAE in Lewis N rats was selected because it is pathologically characterized by focal, very large plaques of demyelination.…”

Section: Discussionsupporting

confidence: 74%

Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis

Kornek

Storch

Weissert

et al. 2000

The American Journal of Pathology

839

188

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Recent magnetic resonance (MR) studies of multiple sclerosis lesions indicate that axonal injury is a major correlate of permanent clinical deficit. In the present study we systematically quantified acute axonal injury, defined by immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in the central nervous system of 22 multiple sclerosis patients and 18 rats with myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune encephalomyelitis (EAE). The highest incidence of acute axonal injury was found during active demyelination, which was associated with axonal damage in periplaque and in the normal appearing white matter of actively demyelinating cases. In addition, low but significant axonal injury was also observed in inactive demyelinated plaques. In contrast, no significant axonal damage was found in remyelinated shadow plaques. The patterns of axonal pathology in chronic active EAE were qualitatively and quantitatively similar to those found in multiple sclerosis. Our studies confirm previous observations of axonal destruction in multiple sclerosis lesions during active demyelination, but also indicate that ongoing axonal damage in inactive lesions may significantly contribute to the clinical progression of the disease. The results further emphasize that MOG-induced EAE may serve as a suitable model for testing axon-protective therapies in inflammatory demyelinating conditions.

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Section: Discussionsupporting

confidence: 74%

Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis

Kornek

Storch

Weissert

et al. 2000

The American Journal of Pathology

839

188

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“…Several decades later, the dilemma of persistance or loss of axons has also found attention in English literature (18,32,44,56). By reviewing earlier studies, T. Putnam noted: "The persistance of axons is such a cardinal point in the pathologic picture that many articles on the subject leave the impression that all are intact in all sclerotic plaques.…”

Section: Axonal Pathology In Multiple Sclerosis a Historical Notementioning

confidence: 99%

Axonal Pathology in Multiple Sclerosis. A Historical Note

1999

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“…Within the lesions, or plaques, that are a hallmark of the disease there is an in¢ltrate of T lymphocytes and macrophages, damage to the blood^brain barrier and myelin loss. There is also, however, clear evidence that in a proportion of lesions there is loss of axons and indeed in some acute aggressive forms of the disease it is accepted that there is severe loss of axons (Charcot 1877;Doinikow 1915;Putnam 1936;Green¢eld & King 1936;Lassmann, this issue). The central question to be addressed is not whether there is axonal loss in MS but when and to what extent does the axonal loss occur ?…”

Section: Introductionmentioning

confidence: 99%

Axon damage and repair in multiple sclerosis

Perry

Anthony

1999

Phil. Trans. R. Soc. Lond. B

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It is well known that within long-standing multiple sclerosis (MS) lesions there is axonal loss but whether it is an early or late event has been more di¤cult to establish. The use of immunocytochemical methods that reveal axonal end-bulbs is a valuable approach to investigating acute axonal injury in human pathological material. The application of these techniques to multiple sclerosis tissue reveals evidence of axonal injury in acute lesions; the distribution of the end-bulbs in acute and active-chronic lesions is associated with regions of maximal density of in¢ltrating macrophages. Axon injury within the MS lesion will result in both Wallerian degeneration of the axon and also retrograde degeneration of the cell body. The functional consequences of the axon injury will depend upon numbers of axons injured and the topographical organization of the ¢bres coursing through the lesion.The molecular mechanisms by which the recruited leucocytes damage or transect the axons are not known. However, investigations in the Wld mutant mouse with very slow Wallerian degeneration demonstrate that axon degeneration is not simply a passive disintegration of the axon but has clear parallels with the active processes of programmed cell death. The presence of early axon injury and the consequences of an ever increasing load of neuronal damage has important implications not only for when therapy should be initiated in MS but also the therapeutic target.

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Studies in Multiple Sclerosis

Cited by 65 publications

References 19 publications

Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis

Multiple Sclerosis and Chronic Autoimmune Encephalomyelitis

Axonal Pathology in Multiple Sclerosis. A Historical Note

Axon damage and repair in multiple sclerosis

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