Experimental Study of Diphtheritic Polyneuritis in the Rabbit and Guinea Pig

Diphtheritic polyneuritis was induced in guinea pigs by injection of incompletely neutralized toxin-antitoxin mixture. At varying intervals after the injection, simples of peripheral nerves from these animals were incubated in Warburg vessels in the presence of a labelled lipide precursor (acetate or phosphate); the total lipides were then extracted and counted. Nerve preparations from litter mate pair-fed animals served as controls. Histologically, no damage was observed until 6 or 7 days after the injection, at which time some fibers began to show segmental demyelination. From the fifth day onward there was a slow decrease in total nerve lipide content and a slight decrease in percentage dry weight. Oxygen uptake was slightly depressed at 5 days, and moderately elevated from 15 days onwards. The incorporation of acetate into the total lipides was profoundly and persistently depressed, a measurable decrease being apparent as early as 24 hours. The incorporation of phosphate into the lipides tended to increase only in the later stages of the disease, when fibers undergoing Wallerian degeneration were found admixed with those showing the characteristic segmental demyelination. These biochemical changes were interpreted as a manifestation of an early and persistent depression of the function of myelin maintenance, in the absence of any stimulus to the Schwann cell. This situation was contrasted with the changes previously found in Wallerian degeneration, in which the depression of myelin maintenance is accompanied by hypertrophy and hyperplasia of the Schwann cells. When liver slices from normal and treated animals were incubated under the same conditions as the nerves, no significant difference was found in the rates of incorporation of the label. Normal nerves and white matter, incubated for 4 hours in the presence of large amounts of toxin, were not demonstrable affected. Starvation alone was found to have considerable effect on lipide biosynthesis in peripheral nerves. After 5 days of partial food restriction, the rate of incorporation of acetate was reduced to one-half the control value, while histologically the nerves appeared normal.