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. 2006 Apr 5;15(3):198–207. doi: 10.1111/j.1750-3639.2005.tb00521.x

Failure of Remyelination in the Nonhuman Primate Optic Nerve

François Lachapelle 4,1, Corinne Bachelin 4,1, Pierre Moissonnier 2, Brahim Nait‐Oumesmar 1, Antoine Hidalgo 2, Denys Fontaine 3, Anne Baron‐Van Evercooren 1,✉
PMCID: PMC8096034  PMID: 16196386

Abstract

The mechanisms limiting myelin repair in human central nervous system (CNS) remain unknown. Models of induced‐demyelination in the nonhuman primate CNS may provide the necessary grounds to unravel these mechanisms and to investigate the development of strategies to promote myelin repair. To address this issue, we developed a model of focal demyelination in the adult Macaca fascicularis CNS. Lesions were induced by microinjection of lysolecithin in the optic nerve and the profile of remyelination was compared to that of lysolecithin‐induced lesions of the spinal cord. In both structures, the time‐course of demyelination as well as the onset of remyelination were found to be similar to that in the rodent CNS. While spinal cord lesions were remyelinated within 6 weeks, optic nerve lesions remained demyelinated for up to 3 months post‐injection. The failure of remyelination in the optic nerve correlated with a reduced density of NG2′ oligodendrocyte progenitor cells, the presence of oligodendrocytes that fail to ensheath naked axons in the lesion and the absence of astrocyte recruitment in the lesion compared with spinal cord lesions. Our present data suggest that the reduced oligodendrocyte progenitor population, the improper activation of oligodendrocytes at the onset of remyelination in the optic nerve, and possibly, the involvement of astrocytes contribute to the chronicity of the optic nerve lesion. This model of chronic demyelination in the macaque optic nerve stress its pertinence to unravel the mechanisms limiting remyelination in multiple sclerosis.

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