Journal of Neuroscience, Vol 14, 357-367, Copyright © 1994 by Society for Neuroscience
Fate of myelin lipids during degeneration and regeneration of peripheral nerve: an autoradiographic study
JF Goodrum, T Earnhardt, N Goines and TW Bouldin
Brain and Development Research Center, University of North Carolina at Chapel Hill 27599.
Four weeks after labeling myelin lipids with an intraneural injection of
3H-acetate, sciatic nerves were crushed, and the distribution of
radiolabeled myelin lipids was followed by autoradiography from 1 d to 10
weeks later. Just prior to crush, silver grains were localized to the
myelin sheath. Three days after crush, axons were degenerating and myelin
sheaths were breaking down; silver grains appeared over lipid droplets
within Schwann cells, fibroblasts, and macrophages. One week after crush
the basal-lamina-delimited Schwann-cell tubes (Bungner bands) contained
myelin debris, and some tubes already contained regenerating axons. Schwann
cells were often displaced to the periphery of the tubes by phagocytes
containing heavily labeled myelin debris; extratubal macrophages within the
endoneurium contained labeled lipid droplets but no myelin debris. Two
weeks after nerve crush silver grains were associated with newly formed
myelin around regenerating axons. Many extratubal endoneurial macrophages
now contained labeled myelin debris and lipid droplets. By 3 weeks
myelination of regenerating axons was advanced, and the myelin sheaths were
well labeled. Extratubal macrophages had become the major labeled structure
within the nerve because they contained large amounts of labeled myelin
debris and lipid droplets. From 4 to 10 weeks after nerve crush the new
myelin sheaths continued to thicken and to be well labeled. Debris- laden
extratubal macrophages remained the major site of labeled material within
the endoneurium. Our results confirm that there is reutilization of myelin
cholesterol by Schwann cells to form new myelin, and indicate that some
lipid catabolism takes place in Schwann cells and endoneurial fibroblasts
prior to infiltration of the nerve by macrophages. However, most of the
myelin debris is phagocytized by macrophages within 1-2 weeks following
nerve injury. These debris-laden macrophages persist within the nerve for
many weeks, indicating that much of the salvaged cholesterol is not
reutilized for myelin regeneration.
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