Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination

An association between macrophages and remyelination efficiency has been ob served in a variety of different models of CNS demyelination. In order to t est whether this association is causal or coincidental, we have examined th e effects of macrophage depletion on the rate of remyelination of lysolecit hin-induced demyelination in the spinal cord of young adult female rats. Ma crophage depletion was achieved by reducing the monocyte contribution to th e macrophages within the lesion using the clodronate-liposome technique. Th is technique not only resulted in a decrease in Ox-42-positive cells in the spleen of treated animals but also in the levels of macrophage scavenger r eceptor type B mRNA expression within the demyelinating lesion. In animals treated with clodronate-liposomes throughout the remyelination process, the re was a significant decrease in the extent of oligodendrocyte remyelinatio n at 3 weeks after lesion induction, but no effect on Schwann cell remyelin ation. If macrophage depletion was delayed until the second half of the rem yelination phase, then there was no effect on the repair outcome, implying that macrophages are required for the early stages of CNS remyelination. Th e results of this study indicate that the macrophage response is an importa nt component of successful CNS remyelination and that approaches to the tre atment of demyelinating disease based on inhibition of the inflammatory res ponse may also impair regenerative events that follow demyelination. (C) 20 01 Wiley-Liss, Inc.