The Origin of Remyelinating Oligodendrocytes in Antiserum-Mediated Demyelinative Optic Neuropathy

Abstract

The origin of the remyelinating oligodendrocyte in a focal antigalactocerebroside-induced demyelinating lesion of the cat optic nerve was studied with detailed correlative electron microscopy and immunocytochemistry using a panel of antigenic markers. Within 10 days of the destruction of all endogenous oligodendrocytes and demyelination of all axons in the lesion, a new population of small glial cells appeared coincident with division of the residual astrocytes and developed a process-bearing axon-embracing morphology. The processes of these small glial cells (SGCs) contained intermediate filaments composed not of glial fibrillary acidic protein but of vimentin and over the ensuing 14 days these cells confirmed their oligodendrocyte destiny by differentiating to lose the intermediate filaments, form myelin and acquire the acquire the typical oligodendrocyte antigenic phenotype. It is suggested that the extensive remyelination of this lesion is sponsored by the new population of SGCs which in turn are generated either by dedifferentiated reactive astrocytes or by as yet unidentified precursor cells.

Inflammation and the brain

“…An obvious candidate is the adult O-2A progenitor (Wolswijk and Noble, 1989), which responds to platelet-derived and fibroblast growth factors, and retains proliferative and migratory potential, raising the possibility that manipulating growth factor conditions and limiting the processes involved in tissue injury might create an environment in which areas of demyelinated axons could be repopulated and remyelinated. A remyelinating cell having the cell surface phenotype of committed oligodendrocytes (04 positive) has been identified in the acute demyelinating lesions of multiple sclerosis (Prineas et al, 1989), and in experimental demyelination of the feline and murine optic nerve (Godfraind et al, 1989;Armstrong et al, 1990;Carroll et al, 1990).…”

Human oligodendrocyte precursor cells in vitro: Phenotypic analysis and differential response to growth factors

“…The success of therapeutic strategies aimed at augmenting this repair process, either by manipulating potential remyelinating cells in situ or by glial cell transplantation after expansion in vitro, requires indepth knowledge of the cells responsible for remyelination and of the growth factors involved. In rodents, prevailing evidence increasingly favors the hypothesis that surviving or locally-derived oligodendrocyte precursor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes (Ludwin, 1979;Godfraind et al, 1989;Armstrong et al, 1990a;Carroll et al, 1990, Armstrong et al, 1998Rodriguez et al, 1991;Prayoonwiwat and Rodriguez, 1993;Capello et al, 1997;Gensert and Goldman, 1997;Keirstead and Blakemore, 1998;Di Bello et al, 1999). Proliferating OPCs were first described in cultures of developing rat optic nerve (Raff et al, 1983).…”

Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord

“…Furthermore, it is unlikely that myelinsupporting oligodendrocytes in the vicinity of a lesion are capable of division, migration, and repopulation of the lesion. Cells with the morphological characteristics of immature glia have been reported within and bordering experimental lesions (Blakemore, 1972;Blakemore and Patterson, 1978;Carroll et al, 1990;Ludwin, 1978;Rodriguez and Lennon, 1990), as well as MS lesions (Prineas et al, 1989). Oligodendrocyte progenitor cells are present within the adult CNS (ffrench-Constant and Raff, 1986;Wolswijk and Noble, 1989), are capable of division (Noble et al, 1988) and migration (Noble et al, 1988), and can remyelinate experimentally induced regions of demyelination following transplantation (Franklin, 1993).…”

“…This paucity of information stems from a lack of suitable markers for oligodendrocyte progenitor cells in tissue sections. Although immature oligodendrocyte precursors bind the antibodies A2B5 (Raff et al, 1983), LB 1 (to the G D3 ganglioside; Gonye et al, 1994), 04 (Sommer and Schachner, 1981), NSP-4 (ffrench-Constant andRaff, 1986), anti-J1 (ffrench-Constant andRaff, 1986), and anti-vimentin (Carroll et al, 1990), the use of most of these antibodies in tissue sections is limited due to their reactivity with other cell types. Antibodies to G D3 , for example, also react with antigens present on amoeboid and reactive microglia (Milligan et al, 1991;Perry and Gordon, 1991;Wolswijk, 1994).…”