Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system.
High dose corticosteroid (CS) administration is a common mode of therapy in treatment of acute relapses in multiple sclerosis (MS) but the effects of CS on remyelination and the cellular mechanisms mediating this repair process are controversial. We have examined CS effects on repair of toxin-induced demyelinating lesions in the adult rat spinal cord. Corticosteroids reduced the extent of oligodendrocyte remyelination at 1 month post lesion (whereas Schwann-cell mediated repair was unaffected). However, CS did not cause permanent impairment of remyelination as lesions were fully remyelinated at 2 months after cessation of treatment. The delay in oligodendrocyte mediated repair could be attributed to inhibition of differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes, with no effect of CS treatment observed on OPC colonisation of the lesions. No differences were observed in animals treated with methylprednisolone succinate alone or with a subsequent prednisone taper indicating that CS effects occur at an early stage of repair. The potential consequences of delayed remyelination in inflammatory lesions are discussed.
Chari
Divya M
DM
Cambridge Centre for Brain Repair and Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom. dmc35@hermes.cam.ac.uk
Zhao
Chao
C
Kotter
Mark R
MR
Blakemore
William F
WF
Franklin
Robin J M
RJ
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004996:Ethidium; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D010587:Phagocytosis; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology
D000305:Adrenal Cortex Hormones; D005904:Glial Fibrillary Acidic Protein; D004996:Ethidium