Conditioning lesions of peripheral nerves change regenerated axon numbers.

The present study investigates the effects of conditioning lesions on regenerated axon numbers in tributary nerves after a test lesion. If a rat sciatic nerve is crushed 7 and 14 days prior to a test crush, the numbers of regenerated myelinated axons 8 weeks later in the sural nerve (SN) and nerve to the medial gastrocnemius (NMG) are increased, both over normal and over numbers after a single crush. If the lesions are only separated by 2 days, however, the numbers are similar to the numbers after a single crush. Thus conditioning occurs, but a minimum time between crushes is necessary for the effects of conditioning to be manifest. If the intervals between lesions are 14 days, the numbers are similar to those after the 7-day intervals. Moving each successive crush proximally or distally does not change regenerated myelinated axon numbers. Thus increasing the time between lesions after conditioning occurs, at least within the constraints of our paradigm, does not change regenerated axon numbers and the location of the lesion has relatively little bearing on the numbers of axons that regenerate. These findings allow us to change axonal numbers in these tributary nerves in a predictable way, and they are also compatible with the hypothesis that conditioning results from priming of the cell body rather than changes in the environment of the regenerating axons.

Numerical patterns of axon regeneration that follow sciatic nerve crush in the neonatal rat.

Different proportions of axons regenerate in cutaneous nerves compared with muscle nerves after sciatic nerve crush in the rat. The questions here are whether or not these differences reflect the proportions of axons that regenerate in the different nerves from which these nerves arise and do the differences persist. The findings indicate that the numbers of axons that regenerate in the muscle nerves do not reflect the numbers in the nerve from which the muscle nerves originate and that these differences persist. This leads to the conclusion that some factors determining numbers of axons in the muscle nerves must operate distal to the lesion. Thus when one is considering mechanisms that control regenerated axon numbers after neonatal nerve crush, one must consider not only the lesion site but also branching and axon diversion far distally, presumably at the origin of the muscle nerves.

Nerve regeneration changes with filters of different pore size.

An experimental reason for placing stumps of a transected nerve in an impermeable tube is that factors and soluble substances from the nerve stumps are pooled and separated from cells and soluble substances in the body in general. Previous work showed that certain parameters of regeneration were improved, however, when the impermeable tube was made completely permeable by cutting macroscopic holes in its side. To begin exploring the reasons for these improvements, we covered the holes in the permeable tubes with filters of two different pore sizes, and found that the improvements resulted when the pore size was large enough to allow both fluid and cells to exchange but not when the pore size allowed only fluid to exchange. These findings suggest that cells from the general connective tissue should be given consideration when designing experimental procedures to maximize the regeneration potential of regenerating axons.