Differential vulnerability of mixed and cutaneous nerves in lead neuropathy

The prevalence of demyelinated fibers in mixed nerve (sciatic) and cutaneous nerve (sural) and the change in lead levels in various tissues over time were assessed in a model of lead neuropathy in the rat. Long-Evans rats were given drinking water containing 4% lead acetate and killed between one and 213 days of exposure. Lead levels in blood, brain, kidney, and femur increased over the 213-day period. Lead levels in sciatic nerve appeared to increase rapidly during the first few weeks of exposure and then decline to a lower plateau. The neuropathy was characterized by segmental demyelination and remyelination; neither axonal degeneration nor a microangiopathy was found. Sciatic nerve had a significantly greater prevalence of demyelinated fibers than sural nerve; the prevalence of demyelinated fibers was similar in proximal and distal sciatic nerve. The variable, brain-lead concentration times days on lead, which is an indicator of cumulative brain exposure, was the best predictor of the prevalence of demyelination. The differential involvement of sciatic and sural nerves in lead neuropathy may either indicate that Schwann cells myelinating different nerve-fiber populations have different susceptibilities to lead toxicity, or that lead preferentially enters sciatic nerve.