Survival and subsequent regeneration of olfactory neurons after a distal axonal lesion.

Abstract

If an axonal lesion is made close enough to the cell body, injured olfactory neurons degenerate and are replaced by new nerve cells arising from undifferentiated mucosal basal cells. Therefore, under these conditions neural regeneration occurs through a process similar to neuronal development. The use of the long garfish olfactory nerve has revealed that neuronal death is not an inevitable consequence of an axonal injury and that the extent of cell death depends on the distance between the site of injury and the perikaryon. A lesion located up to 40 mm from the cell body induces the death of all mature neurons. Between 60 and 100 mm an increasing proportion of neurons survive the injury (from 60 to more than 90%) and are able to regenerate their distal segment. During regeneration, two populations of growing axons have been characterized. The fastest growing fibres (5.8 mm per day) correspond to the small population of neurons which were already growing at the time of the lesion and are able to survive an injury at any distance along the nerve. The majority of the regenerating fibres grow at 0.8 mm per day and corresponds to the damaged mature neurons. Elongation velocities were not affected by the distance from injury to cell body or by the mode of neural repair (development or regeneration). The initial delay between the injury and the beginning of elongation increases linearly with distance at a rate of 1 day cm-1 and is independent of the elongation velocity of the growing neurons. This indicates that the mechanism responsible for the beginning of axonal growth is initiated at or near the cell body and involves the entire axonal stump and not only the area surrounding the crush site. The ability of nerve cells to survive an injury may depend on the length of the axonal stump remaining attached to the cell body and on the level of protein synthesis at the time of the crush. From preliminary results it can be hypothesized that the length of the initial delay is determined by a reorganization of the cytoskeletal elements in the proximal axonal stump.