FATE OF MYELIN LIPIDS DURING DEGENERATION AND REGENERATION OF PERIPHERAL-NERVE - AN AUTORADIOGRAPHIC STUDY

Four weeks after labeling myelin lipids with an intraneural injection of H-3-acetate, sciatic nerves were crushed, and the distribution of r adiolabeled myelin lipids was followed by autoradiography from 1 d to 10 weeks later. Just prior to crush, silver grains were localized to t he myelin sheath. Three days after crush, axons were degenerating and myelin sheaths were breaking down; silver grains appeared over lipid d roplets within Schwann cells, fibroblasts, and macrophages. One week a fter crush the basal-lamina-delimited Schwann-cell tubes (Bungner band s) contained myelin debris, and some tubes already contained regenerat ing axons. Schwann cells were often displaced to the periphery of the tubes by phagocytes containing heavily labeled myelin debris; extratub al 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 ex tratubal endoneurial macrophages now contained labeled myelin debris a nd lipid droplets. By 3 weeks myelination of regenerating axons was ad vanced, and the myelin sheaths were well labeled. Extratubal macrophag es had become the major labeled structure within the nerve because the y 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 macrophage s 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 cata bolism takes place in Schwann cells and endoneurial fibroblasts prior to infiltration of the nerve by macrophages. However, most of the myel in debris is phagocytized by macrophages within 1-2 weeks following ne rve injury. These debris-laden macrophages persist within the nerve fo r many weeks, indicating that much of the salvaged cholesterol is not reutilized for myelin regeneration.