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.

We investigated the temporal course of blood-nerve barrier (BNB) breakdown during the evolution of tellurium neuropathy, ricin neuropathy, and Wallerian degeneration following nerve transection or nerve crush. Blood-nerve barrier permeability was assessed with a 4,000-molecular weight fluoresceinated dextran from three days to 19 weeks after onset of neuropathy. Blood-nerve barrier breakdown was present during the first two weeks in all four models of neuropathy. Restoration of the BNB to the dextran began within four weeks and was complete by 14 weeks in tellurium neuropathy, a model of demyelinating neuropathy characterized by rapid remyelination, and after nerve crush, a model of Wallerian degeneration characterized by rapid axonal regeneration into distal stump. In contrast, there was persistence of BNB breakdown beyond 14 weeks in ricin neuropathy, a model of neuropathy with no axonal regeneration or remyelination, and after nerve transection, a model of Wallerian degeneration characterized by minimal axonal regeneration into distal stump. We conclude from these data that alterations in the BNB over the course of neuropathy differ among various types of neuropathy, and that these alterations are dependent on the form of nerve fiber injury. The lack of regenerating or remyelinating axons in ricin neuropathy and after nerve transection may be responsible for the persistent BNB breakdown found in these neuropathies.

No abstract

Following nerve crush, cholesterol from degenerating myelin is conserved and reutilized for new myelin synthesis during nerve regeneration. The possibility that other myelin lipids are salvaged and reutilized has not been investigated previously. We examined the fate of myelin phospholipids and their fatty acyl moieties following nerve crush by electron microscopic autoradiography of myelin lipids prelabeled with [3H]oleate or [2‐3H]‐glycerol. Both precursors were incorporated predominantly (>90%) into phospholipids; >85% of the [3H]oleate was incorporated as oleate, with the remainder in longer‐chain fatty acids. Before nerve crush, both labels were restricted to myelin sheaths. Following nerve crush and subsequent regeneration, over half the label from [3H]oleate, but little from [2‐3H]glycerol, remained in nerve. The oleate label was present as fatty acyl moieties in phospholipids and was localized to newly formed myelin sheaths. Among the extracellular soluble lipids within the degenerating nerve, the bulk of the labeled phospholipids floated at the same density as lipoprotein particles. These data indicate that myelin phospholipids are completely hydrolyzed during nerve degeneration, that at least half the resultant free fatty acids are salvaged and reutilized for new myelin synthesis, and that these salvaged fatty acids are transported by a lipoprotein‐mediated mechanism similar to that functioning in cholesterol reutilization.