Document Detail

Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination.
MedLine Citation:
PMID:  15589038     Owner:  NLM     Status:  MEDLINE    
Minocycline, a tetracycline derivative, disrupts inflammatory processes within the CNS and reduces demyelination in experimental autoimmune encephalomyelitis. Several recent studies indicate that components of the inflammatory response to demyelination may be beneficial for the regenerative process of remyelination. In this study we examined the effects of minocycline on remyelination independent of its effects in limiting immune-mediated white matter damage using a toxin model of demyelination. Demyelinating lesions were induced by injection of ethidium bromide into caudal cerebellar peduncles of adult rats. Minocycline or PBS was administered by twice daily injections from day 1 prior to lesion-induction to post lesion day 3. Remyelination was assessed, blinded to grouping, using standard morphological criteria. The microglia activation within the lesion was assessed by examining the expression of OX-42 and major histocompatibility class II immunoreactivity. The oligodendrocyte progenitor cell (OPC) response was quantified by in situ hybridization using probes for OPC-expressed mRNAs, platelet-derived growth factor receptor-alpha and Olig-1. Minocycline treatment strongly inhibited microglia/macrophage activation at day 1 and day 3 post-lesion induction, and suppressed the OPC response to demyelination. We also found a significant decrease in the extent of oligodendrocyte but not Schwann cell remyelination in the minocycline-treated animals as compared with controls at 3 weeks post-lesion induction. These results indicate that microglia/macrophage activation is an important process for remyelination and further support the concept that suppression of inflammatory response may impair remyelination.
Wen-Wu Li; Anna Setzu; Chao Zhao; Robin J M Franklin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroimmunology     Volume:  158     ISSN:  0165-5728     ISO Abbreviation:  J. Neuroimmunol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-13     Completed Date:  2005-03-07     Revised Date:  2011-11-03    
Medline Journal Info:
Nlm Unique ID:  8109498     Medline TA:  J Neuroimmunol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  58-66     Citation Subset:  IM    
Cambridge Centre for Brain Repair and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
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MeSH Terms
Animals, Newborn
Anti-Bacterial Agents / therapeutic use*
Antigens, CD11b / metabolism
Bromodeoxyuridine / metabolism
Cell Count
Cells, Cultured
Cerebellum / metabolism
Demyelinating Diseases / chemically induced,  drug therapy*,  metabolism
Disease Models, Animal*
Dose-Response Relationship, Drug
Fluorescent Antibody Technique / methods
Genes, MHC Class II / physiology
In Situ Hybridization / methods
Microglia / drug effects*
Minocycline / therapeutic use*
Oligodendroglia / drug effects*
Staining and Labeling / methods
Stem Cells / drug effects
Time Factors
Grant Support
689//Multiple Sclerosis Society
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antigens, CD11b; 10118-90-8/Minocycline; 3546-21-2/Ethidium; 59-14-3/Bromodeoxyuridine

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