Demyelination and remyelination of the caudal cerebellar peduncle of adultrats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: A comparative study

Experimentally induced demyelination due to the direct injection of gliotox ic agents has provided powerful models for studying the biology of remyelin ation. For the most part, these models have involved injection into white m atter tracts of the spinal cord. However, the spinal cord has a number of l imitations, such as the size of lesions that it is possible to make and its unsuitability for long-term direct cannulation for the delivery of putativ e remyelination-enhancing agents. In this study, we describe the natural hi story of three new models of demyelination/remyelination based on the stere otaxic injection of three gliotoxins: lysolecithin, ethidium bromide, and a combination of anti-galactocerebroside antibody and complement (GalC-ab/co mp) into the caudal cerebellar peduncle of adult rats. All three agents pro duced large areas of demyelination with minimal axonal damage, which underg o extensive remyelination. Ethidium bromide- and GalC-ab/comp-induced lesio ns remyelinated more slowly than those induced by lysolecithin. The contrib ution to the remyelination of the lesion by Schwann cells reflects the degr ee of astrocyte damage incurred within the demyelinated area and is greates t for ethidium bromide-induced demyelination. These new models not only pro vide further insights into the mechanisms of CNS remyelination but also pro vide a valuable new resource for addressing a series of key issues relevant to current efforts to promote CNS remyelination either by the enhancement of intrinsic processes or by the transplantation of myelinogenic cells. (C) 1999 Wiley-Liss, Inc.