Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination - PubMed (original) (raw)

Comparative Study

Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination

Wen-Wu Li et al. J Neuroimmunol. 2005 Jan.

Abstract

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.

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Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination - PubMed (original) (raw)