Ibotenic acid induced demyelination in the central nervous system: a consequence of a local inflammatory response

Abstract

We examined the effects of injections of ibotenic acid into the medial septum (MS), dorsal lateral geniculate nucleus (dLGN), caudate-putamen (CP) or fornix-fimbria (FF) on fibres close to the injection site. Injections into the MS and dLGN resulted in demyelination. The area of demyelination correlated with the area of maximal gliosis. The major cell type in the area of gliosis were cells of haemopoietic origin, as revealed by using monoclonal antibodies (Mabs). Demyelination was not observed in the CP or FF. Axonal transport in fibres en passage through the dLGN lesion was also disrupted following injections of horseradish peroxidase (HRP) into the eye contralateral to the lesion. These results show that when ibotenic acid induces cell death it can secondarily damage myelin sheaths and disrupt axonal transport in areas containing diffuse fibre systems. We suggest that this is due to a non-specific effect of the inflammatory response.