galactocerebroside and Central-Nervous-System-Diseases

The mechanism of antibody-mediated central nervous system (CNS) demyelination in vivo was studied using rabbit eyes. Injection of anti-galactocerebroside (Gal C) antiserum alone into the normal rabbit vitreous body induced demyelination in the epiretinal myelinated fibers. This activity of the antiserum disappeared after heat treatment at 56 degrees C for 30 min and was restored by supplement of normal fresh serum, suggesting the complement dependency of the activity. Heated anti-Gal C antiserum could induce demyelination, however, when macrophages were introduced by injecting lymphocyte supernatants together with antiserum. Electron microscopic study revealed penetration of macrophage process between the myelin lamella. These findings suggest that the cooperation of anti-Gal C antibody and macrophage can result in the antibody-dependent cell-mediated demyelination in the absence of complement. Because oligodendrocyte generally appeared normal, myelin, not oligodendrocyte is suspected to be the primary target by anti-Gal C antiserum. In contrast, neither anti-MBP nor anti-gangliosides antiserum had the in vivo-demyelinating activity. In CNS demyelination by anti-Gal C antibody, complement-mediated and macrophage-mediated mechanisms may cooperate in varying degrees.

Topics: Animals; Autoantibodies; Central Nervous System Diseases; Cerebrosides; Demyelinating Diseases; Eye; Galactosylceramides; Male; Rabbits

To study the pathophysiology of immunologically mediated demyelination in the central nervous system (CNS), we injected 20 to 30 microliters of polyclonal antigalactocerebroside serum (AGC) into the lower thoracic dorsal column of the spinal cord in 20 Wistar rats. AGC-injected spinal cords contained areas of fascicular demyelination adjacent to the focus of axonal degeneration at the injection site. Somatosensory evoked potentials were recorded serially after tibial nerve stimulation. In 85% of AGC-injected animals, the following characteristics were observed by 3 days after injection: (1) decreased amplitude of the cortically generated potential (P15); (2) failure of transmission of high-frequency (50 Hz) impulses (rate-dependent block); (3) delayed conduction velocity of the compound action potentials through the lesion. None of these changes was seen in 90% of 20 rats injected with normal saline or control rabbit sera. In 7 rats with acrylamide-induced axonopathy or wallerian degeneration, the rate-dependent block was not observed. The onset of clinical symptoms (hindlimb ataxia) in AGC-injected rats was best correlated with development of the rate-dependent block. Clinical recovery was observed by 14 days after injection concurrent with restoration of P15 amplitude, when the rate-dependent block and decreased conduction velocities were unchanged. High-frequency-resistant conduction was re-established much later than clinical recovery in 3 rats. These findings suggest that failure of high-frequency impulse transmission may produce clinical symptoms and that a central adaptive mechanism to remodulated trains of impulses plays a role in clinical recovery from CNS demyelination.

Topics: Acrylamide; Acrylamides; Animals; Central Nervous System Diseases; Demyelinating Diseases; Evoked Potentials, Somatosensory; Galactosylceramides; Immune Sera; Injections; Neural Conduction; Rats; Reaction Time; Time Factors; Wallerian Degeneration