Failure of remyelination in the nonhuman primate optic nerve.
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 stresses its pertinence to unraveling the mechanisms limiting remyelination in multiple sclerosis.
Lachapelle
François
F
Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie UMR 546, CHU de la Salpetriere, Paris, France.
Bachelin
Corinne
C
Moissonnier
Pierre
P
Nait-Oumesmar
Brahim
B
Hidalgo
Antoine
A
Fontaine
Denys
D
Baron-Van Evercooren
Anne
A
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008252:Macaca fascicularis; D046529:Microscopy, Electron, Transmission; D009103:Multiple Sclerosis / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000648:ultrastructure; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000473:pathology*; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000473:pathology; D013234:Stem Cells / Q000166:cytology
D008244:Lysophosphatidylcholines