Ultrastructural study of central nervous system demyelination in galactocerebroside sensitized rabbits

The rabbit eye model was used to investigate the role of delayed type hypersensitivity and of circulating antigalactocerebroside antibody in primary demyelination. Delayed type hypersensitivity reaction to tuberculin was induced within the retinal myelinated layers by injecting purified protein derivative into the vitreous of rabbits that were previously immunized with complete Freund's adjuvant (CFA) alone, or galactocerebroside (GC) in CFA. The morphological features of the myelinated zones were assessed 5 days after injection. All rabbits showed infiltration of mononuclear cells within the myelinated fiber bundles. Rabbits previously sensitized with CFA alone showed nonspecific destruction of nerve fibers in severe inflammatory lesions, but primary demyelination was rarely found. This suggests that myelin destruction induced by delayed type hypersensitivity reaction to interstitial antigens (purified protein derivative, so-called "bystander demyelination") by itself does not play a major role in inducing primary demyelination. On the other hand, primary demyelination was recognized in the vicinity of infiltrating mononuclear cells in rabbits previously immunized with GC in CFA and had elevated titers of serum anti-GC antibody. The destruction of the blood-brain barrier was suggested by the presence of fibrin exudates in demyelinative lesions where observation revealed selective myelin breakdown such as vesicular disruption and active stripping of myelin. This study indicates that the anti-GC antibody is an important factor in central nervous system demyelination of GC-sensitized rabbits.