Tubulomembranous Lesions in p-Bromophenylacetylurea Neuropathy Reflect Local Stasis of Fast Axonal Transport: Evidence From Electron Microscopic Autoradiography

The source of the membranous materials that accumulate in distal axons of rats intoxicated with p-bromophenylacetylurea (BPAU) was studied by electron microscopy. ³⁵S-Methionine was injected into the ventral horn of the spinal cord at 2, 14, and 35 days after injection of BPAU. Three days later, samples of the deep peroneal nerves were obtained, and autoradiographs of thin cross sections were prepared. Organellar accumulations were absent from vehicle-treated control nerves and rare in the clinically latent period after administration of BPAU. In later stages of neuropathy, approximately 20% of the myelinated axons in any specific section were swollen and packed with tubules, membranes, and mitochondria. Numerous silver grains were located over the accumulated organelles, and the coincidence was statistically significant The results indicate a sporadic local stasis of fast-transported proteins and provide a plausible explanation for axonal damage in BPAU neuropathy.