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Antiserum-mediated demyelination in vivo: a sequential study using intraneural injection of experimental allergic
Abstract:
Primary segmental demyelination accompanied by mononuclear phagocytes was induced by injection of antiserum into rat peripheral nerve, and the morphologic sequence of events was studied. Antisera were obtained from rabbits with experimental allergic neuritis (EAN) produced by the inoculation of emulsified bovine peripheral nerves in complete Freund's adjuvant. Sera were injected directly into rat sciatic nerve to circumvent the blood-nerve barrier. Recipient rats developed sensorimotor paralysis on the side injected with experimental allergic neuritis sera. Intense focal demyelinative lesions resulted from injection of experimental allergic neuritis sera. Control sera obtained from rabbits inoculated with bovine serum albumin in complete Freund's adjuvant did not produce paralysis or demyelination. The earliest change was damage to Schwann cells, seen 20 minutes after antiserum injection. Within a few hours lamellar splitting and vacuolation of myelin began to paranodal regions and Schmidt-Lanterman clefts and there were infiltrating polymorphonuclear cells. By 8 hours without the detectable presence of monocytes or macrophages, myelin vesiculation became advanced and widespread. By 15 hours, endoneurial edema had reached its maximum. Macrophages were found in association with myelinated nerve fibers. From that time through the next 5 days, demyelination progressed to complete denudation of axons by macrophage phagocytosis of myelin. Activated cytoplasm of Schwann cells reinvested demyelinated axons, often in concert with persisting phagocytic macrophages. Peripheral nerve demyelination thus transferred evolved rapidly, and myelin destruction occurred prior to the appearance of monocytes or macrophages. Demyelinating activity was lost after absorption by purified peripheral nerve myelin but not by liver or kidney and was heat-labile and complement dependent (T. Saida, K. Saida, D. H. Silberberg, and M. J. Brown: Nature 272: 639, 1978).