The endoneurial content of lead related to the onset and severity of segmental demyelination

The endoneurial lead and water content was serially evaluated in the nerves of rats fed lead carbonate and related to the onset and severity of segmental demyelination and remyelination. Lead began to accumulate significantly in the endoneurium by 5 days, reached a maximum level (71 microgram/g dry weight) by 34 days, and then fell to the perineurial level (28 microgram/g dry weight) by 3 months. The water content of endoneurium did not become significantly increased until the 50th day. Extensive teased fiber grading of pathologic abnormalities carried out on the same animals showed that segmental demyelination began between the 20th and 35th days and worsened progressively. This provides the first evidence that high endoneurial lead concentration precedes segmental demyelination and nerve edema. It suggests that the random Schwann cell damage is more likely to be due to a direct toxic effect of lead rather than to a factor associated with edema or increased endoneurial pressure. Contrary to our expectations, lead content does not parallel water content, as would be expected if lead entry into the endoneurium were associated with an abrupt breakdown of the blood-nerve barrier. A further new finding is the decrease in endoneurial lead content at a time when edema and the pathologic lesions are progressing. This may suggest the development of lead removal mechanisms.