Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system.
It has been hypothesized that the progressive failure of remyelination in chronic multiple sclerosis is, in part, the consequence of repeated episodes of demyelination at the same site, eventually depleting oligodendrocyte progenitor cells (OPCs) and exhausting the remyelinating capacity. We investigated the effect of previous focal, ethidium bromide-induced demyelination of brain stem white matter (with intervening recovery) on the efficiency of the remyelination process during second and third subsequent episodes of demyelination, and the OPC response during a second episode of demyelination. Previous focal demyelinating lesions followed by recovery did not result in any retardation of the remyelination process, nor did they alter the proportion of Schwann cell versus oligodendrocyte remyelination. The OPC response during remyelination was quantified by in situ hybridization using a probe to platelet-derived growth factor-alpha receptor (PDGF alpha R), an OPC-expressed mRNA. Following recovery from focal, toxin-induced CNS demyelination, the OPC density returned to levels equivalent to those in normal white matter. Further more, there was no depletion of OPCs following repeated episodes of focal, toxin-induced CNS demyelination at the same site. These results indicate that repeated CNS demyelination, which has the opportunity to repair in the intervening period, is not characterized by impaired remyelination or depletion of OPCs.
Penderis
Jacques
J
Cambridge Centre for Brain Repair and Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, UK.
Shields
Simon A
SA
Franklin
Robin J M
RJ
D000818:Animals; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004996:Ethidium; D005260:Female; D017403:In Situ Hybridization; D009186:Myelin Sheath / Q000502:physiology*; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012008:Recurrence; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
D020796:Receptor, Platelet-Derived Growth Factor alpha; D004996:Ethidium