Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system

• Published in: Journal of neuroscience research Vol. 83; no. 4; pp. 594 - 605
• Main Authors: Chari, Divya M., Zhao, Chao, Kotter, Mark R., Blakemore, William F., Franklin, Robin J.M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2006
• Subjects: Adrenal Cortex Hormones - pharmacology; Animals; Central Nervous System - drug effects; Central Nervous System - pathology; corticosteroids; Demyelinating Diseases - chemically induced; Demyelinating Diseases - pathology; demyelination; Ethidium; Female; Glial Fibrillary Acidic Protein - metabolism; Immunohistochemistry; In Situ Hybridization; Macrophages - drug effects; multiple sclerosis; Myelin Sheath - drug effects; oligodendrocyte progenitors; Oligodendroglia - drug effects; Oligodendroglia - pathology; Phagocytosis; Rats; remyelination; Stem Cells - drug effects; Stem Cells - pathology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20763

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. © 2006 Wiley‐Liss, Inc.