Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis.
BACKGROUND
Multiple sclerosis is an inflammatory disease of the central nervous system that destroys myelin, oligodendrocytes, and axons. Since most of the lesions of multiple sclerosis are not remyelinated, enhancement of remyelination is a possible therapeutic strategy that could perhaps be achieved with the transplantation of oligodendrocyte-producing cells into the lesions. We investigated the frequency distribution and configuration of oligodendrocytes in chronic lesions of multiple sclerosis to determine whether these factors limit remyelination.


METHODS
Forty-eight chronic lesions obtained at autopsy from 10 patients with multiple sclerosis were examined immunocytochemically for oligodendrocytes and oligodendrocyte progenitor cells. Using confocal microscopy, we examined the three-dimensional relations between axons and the processes of premyelinating oligodendrocytes.


RESULTS
Thirty-four of the 48 chronic lesions of multiple sclerosis contained oligodendrocytes with multiple extended processes that associated with demyelinated axons but failed to myelinate them. These axons were dystrophic and contained multiple swellings. In some regions, the densities of premyelinating oligodendrocytes (25 per square millimeter of tissue) were similar to those in the developing rodent brain (23 per square millimeter). In the patients with disease of long duration (more than 20 years), there were fewer lesions with premyelinating oligodendrocytes (P<0.001).


CONCLUSIONS
Premyelinating oligodendrocytes are present in chronic lesions of multiple sclerosis, so remyelination is not limited by an absence of oligodendrocyte progenitors or their failure to generate oligodendrocytes. Our findings suggest that in the chronic lesions of multiple sclerosis, the axons are not receptive for remyelination. Understanding the cellular interactions between premyelinating oligodendrocytes, axons, and the microenvironment of lesions of multiple sclerosis may lead to effective strategies for enhancing remyelination.
Chang
Ansi
A
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Tourtellotte
Wallace W
WW
Rudick
Richard
R
Trapp
Bruce D
BD
D000328:Adult; D000368:Aged; D000941:Antigens / Q000032:analysis; D001369:Axons / Q000473:pathology; D001921:Brain / Q000166:cytology / Q000473:pathology*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated; D009836:Oligodendroglia / Q000473:pathology*; D011509:Proteoglycans / Q000032:analysis; D013234:Stem Cells / Q000473:pathology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4