Understanding CNS remyelination: Clues from developmental and regeneration biology

Franklin, R. J. M.; Hinks, G.L.

doi:10.1002/(sici)1097-4547(19991015)58:2<207::aid-jnr1>3.0.co;2-1

Cited by 102 publications

(55 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Franklin and Hinks (36) proposed that thin myelin sheaths in remyelination result from OLs unsheathing mature axons of mature diameter and length. In contrast in normal development, early myelin internodes adapt to changes in axon caliber and length by becoming thicker in diameter, and longer.…”

Section: Discussionmentioning

confidence: 99%

Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function

Duncan

Marik

Broman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The presence of thin myelin sheaths in the adult CNS is recognized as a marker of remyelination, although the reason there is not a recovery from demyelination to normal myelin sheath thickness remains unknown. Remyelination is the default pathway after myelin loss in all mammalian species, in both naturally occurring and experimental disease. However, there remains uncertainty about whether these thin sheaths thicken with time and whether they remain viable for extended periods. We provide two lines of evidence here that thin myelin sheaths may persist indefinitely in long-lived animal models. In the first, we have followed thin myelin sheaths in a model of delayed myelination during a period of 13 years that we propose results in the same myelin sheath deficiencies as seen in remyelination; that is, thin myelin sheaths and short internodes. We show that the myelin sheaths remain thin and stable on many axons throughout this period with no detrimental effects on axons. In a second model system, in which there is widespread demyelination of the spinal cord and optic nerves, we also show that thinly remyelinated axons with short internodes persist for over the course of 2 y. These studies confirm the persistence and longevity of thin myelin sheaths and the importance of remyelination to the longterm health and function of the CNS.axon | oligodendrocyte | remyelination

show abstract

Section: Discussionmentioning

confidence: 99%

Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function

Duncan

Marik

Broman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Activated astrocytes secrete the anti-inflammatory cytokine IL-10 (26), which inhibits the microglia antigen-presenting function, T cell proliferation, and cytokine synthesis by CD4 + T cells. TGF-β is expressed by all glial cells, including astrocytes in vivo and in vitro (36) and is implicated in the remyelination process (37). It deactivated microglia by down-regulating the expression of molecules associated with antigen presentation and production of proinflammatory cytokines, NO, and oxygen free radicals (38).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Ribavirin on Reactive Astrogliosis in Experimental Autoimmune Encephalomyelitis

et al. 2012

View full text Add to dashboard Cite

“…NT3, BDNF, and TGF-␤ are key regulators of oligodendrocyte survival and development (3,4). They are essential for the proliferation and recruitment of OPCs to the demyelinating lesions and for their subsequent differentiation into mature oligodendrocytes (19,20). It is therefore significant that in the present study, cell infiltrations were observed in the SCs of GA-treated mice and their location was not associated with damage, suggesting the involvement of GA-induced cells in the neuroprotective effect of GA on myelin.…”

Section: Discussionmentioning

confidence: 99%

Demyelination arrest and remyelination induced by glatiramer acetate treatment of experimental autoimmune encephalomyelitis

Aharoni¹,

Herschkovitz²,

Eilam

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

The interplay between demyelination and remyelination is critical in the progress of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In the present study, we explored the capacity of glatiramer acetate (GA, Copaxone) to affect the demyelination process and/or lead to remyelination in mice inflicted by chronic EAE, using both scanning electron microscopy and immunohistological methods. Spinal cords of untreated EAE mice revealed substantial demyelination accompanied by tissue destruction and axonal loss. In contrast, in spinal cords of GA-treated mice, in which treatment started concomitantly with disease induction (prevention), no pathology was observed. Moreover, when treatment was initiated after the appearance of clinical symptoms (suppression) or even in the chronic disease phase (delayed suppression) when substantial demyelination was already manifested, it resulted in a significant decrease in the pathological damage. Detection of oligodendrocyte progenitor cells (OPCs) expressing the NG2 or O4 markers via colocalization with the proliferation marker BrdU indicated their elevated levels in spinal cords of GA-treated mice. The mode of action of GA in this system is attributed to increased proliferation, differentiation, and survival of OPCs along the oligodendroglial maturation cascade and their recruitment into injury sites, thus enhancing repair processes in situ.multiple sclerosis ͉ neuroprotection ͉ oligodendrocyte ͉ myelin repair

show abstract

Understanding CNS remyelination: Clues from developmental and regeneration biology

Cited by 102 publications

References 74 publications

Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function

Thin myelin sheaths as the hallmark of remyelination persist over time and preserve axon function

The Effect of Ribavirin on Reactive Astrogliosis in Experimental Autoimmune Encephalomyelitis

Demyelination arrest and remyelination induced by glatiramer acetate treatment of experimental autoimmune encephalomyelitis

Contact Info

Product

Resources

About