Degenerative and regenerative changes in the trochlear nerve of goldfish

Abstract

The features of unlesioned and lesioned trochlear nerves of goldfish have been examined electron microscopically. Lesioned nerves were studied between 1 and 107 days after cutting or crushing the nerve. Unlesioned nerves contained, on average, 77 myelinated axons and 19 unmyelinated axons. The latter were found in 1–2 fascicles per nerve. A basal lamina surrounded each myelinated axon and fascicle of unmyelinated axons. The numbers of myelinated axons, fascicles of unmyelinated axons and basal laminae varied by less than 5% over the intraorbital extramuscular segment of the nerve. Following interruption of the nerve, by either cutting or crushing, all of the axons and their myelin sheaths began to degenerate by 4 days in the distal nerve-stump. Both abnormally electron-dense and electron-lucent axons were observed. Both Schwann cells and macrophages appeared to phagocytose the myelin sheaths. Following a lesion, the Schwann cells and their basal laminae persisted in the distal nerve-stump. In crushed nerves, the basal laminae surrounding myelinated axons formed 97%, on average, of the Schwann tubes in the distal stump. The perimeters of the basal laminae were of similar size to those in the proximal stump, at least for the first 8 days after crush. In crushed nerves, single myelinated axons in the proximal nerve-stump gave rise to multiple sprouts, some of which reached the site of crush by 2 days, the distal stump by 4 days and the superior oblique muscle by 8 days. The regeneration of the unmyelinated axons was not examined. In both crushed and transected nerves, nearly all of the sprouts in the proximal and distal stumps were found within the basal laminae of Schwann cells, even though the sprouts were disorganized in the transected region where there were no basal laminae. The growth cones of the regenerating axons were always found apposed to the inner surface of the basal laminae, which may have provided an adhesive substrate that directed their growth. Terminal sprouts from the ends of myelinated axons in the proximal stump accounted for the majority of the regenerating axons in the distal stump, as only a few collateral sprouts were found in the proximal stump, and only a small amount of axonal branching was found within the distal stump itself. The largest axons in the distal stump were remyelinated first, and the number of remyelinated axons increased progressively between 8 and 31 days after crush, at which time there were about twice as many as in unlesioned nerves. The number of remyelinated axons remained constant at least until 107 days, the longest time considered, and none was observed to degenerate, whereas some axons that were not remyelinated appeared to degenerate. Although each basal lamina in the distal stump often surrounded several regenerating axons during the first 2 weeks post-lesion, each remyelinated axon became individually surrounded by a basal lamina, collagen fibres and extracellular space between 13 and 107 days, thereby increasing the number of basal laminae in the distal stump. Regenerated axonal terminals in the superior oblique were first observed 8 days after crush. The number of synapses increased progressively between 8 and 107 days, at which time they were as numerous as in unlesioned animals.