THE OUTWANDERING OF CELLS IN TISSUE CULTURES OF NERVES UNDERGOING WALLERIAN DEGENERATION

Abstract

1. The technique of tissue culture has been applied to a study of the physiological changes undergone by the cells of a severed nerve. The sciatic nerve of adult rabbits was cut in the middle of the thigh and pieces of the central and peripheral stump were explanted at varying times after the original cut. The ‘activity’ of a part of a nerve is expressed as the amount of outwandering of the Schwann cells and fibroblasts after 4 days in vitro. 2. In general, except in the terminal bulbs (derived from the herniated ends of the cut nerve) Schwann cell and fibroblast activity changes in a similar way. 3. In the conditions of our experiments normal (undegenerated) nerve shows activity only very rarely. Such activity as does sometimes occur can be explained by the presence of a few degenerate fibres. 4. In the peripheral stump Schwann cell activity begins on the 2nd day after cutting and from the 4th day rises rapidly to a peak at the 19th-25th day. It then falls quickly up to about the 60th day and afterwards more slowly. Activity is still appreciable more than a year after cutting. These changes of activity with time of degeneration are shown by thigh, knee and shank regions of the peripheral stump. The knee region, and the shank (which is 8 cm. distal to the initial cut) are more active than the thigh region, especially in the early days of degeneration. 5. In the central stump activity is at first confined to a few mm. immediately adjacent to the cut. From the 2nd to, the 4th day after cutting the central stump is more active than the peripheral stump, but thereafter it is much less active. Its maximum activity, never, except for the bulb fibroblasts, more than 10% of the maximum activity of the peripheral stump, is reached probably between 5 and 10 days after cutting, after which it falls slowly. Activity is still appreciable more than a year after the cut was made. The more proximal part of the central stump, at first inactive, begins to show slight Schwann cell activity after 23 days and is still active after more than a year. 6. The ½ cm. of the peripheral stump near the cut, including the bulb, is at first more active than the adjacent more distal region. But after degeneration of a year or more the peripheral bulb becomes on the contrary less active than the rest of the peripheral stump. 7. There is a particularly high fibroblast activity in the terminal bulbs of both peripheral and central stumps during the first 2-4 months, probably as a result of an early invasion from the neighbouring connective tissue. Relative to Schwann cell activity the bulb fibroblasts are most active during the 2nd-5th days of degeneration. 8. The schwannoma and neuroma in general show the same changes of activity as the bulbs from which they are formed. Almost no activity was found after degeneration of about a year. In the schwannoma no Schwann cells appear until the 6th day of degeneration, though fibroblasts are very active before this. 9. It is concluded that activation of the Schwann cells and fibroblasts is due to ( a ) degeneration of the nerve fibres, ( b ) in the region close to the cut, a traumatic effect of cutting the nerve, superimposed on ( a ). 10. Since Schwann cells probably play an important part in forming the junction when severed nerves are repaired this work indicates the optimum time from this point of view for making grafts or sutures. Our experiments indicate that the Schwann cells will be more active in joining together two nerve stumps if the nerve or nerve graft is left a few (say 10-20) days to degenerate before making the repair; and that (in the rabbit) the optimum time for suture is passed 25 days after the nerve is cut. Beit Memorial Research Fellow.