Regrow th of the axons (motor, sensory, and autonomic) is possible in peripheral nerves and appears to depend on the presence of endoneurial tubes and the special qualities possessed by Schw ann cells. Sprouts from the axons grow from the proximal stump and into the distal stump tow ard the nerve's end-organs. The follow ing mechanisms are thought to be involved: (1) the axons are attracted by chemotropic factors secreted by the Schw ann cells in the distal stump, (2) grow th-stimulating factors exist w ithin the distal stump, and (3) inhibitory factors are present in the
perineurium to inhibit the axons from leaving the nerve.
The satisfactory regeneration of axons and the return of normal function depend on the follow ing factors:
1. In crush nerve injuries, w here the axon is divided or its blood supply has been interfered w ith but the endoneurial sheaths remain intact, the regenerative process may be very satisfactory.
2. In nerves that have been completely severed, there is much less chance of recovery because the regenerating fibers from the proximal stump may be directed to an incorrect destination in the distal stump—that is, cutaneous fibers entering incorrect nerve endings or motor nerves supplying incorrect muscles.
3. If the distance betw een the proximal and distal stumps of the completely severed nerve is greater than a few millimeters or the gap becomes filled w ith proliferating fibrous tissue or is simply filled by adjacent muscles that bulge into the gap, then the chances of recovery are very poor. The outgrow ing axonal sprouts escape into the surrounding connective tissue and form a tangled mass or neuroma. In these cases, early close surgical
approximation of the severed ends, if possible, greatly facilitates the chances of recovery.
4. When mixed nerves (those containing sensory, motor, and autonomic fibers) are completely severed, the chances of a good recovery are very much less than w hen the nerve is purely sensory or purely motor. The reason for this is that the regenerating fibers from the proximal stump may be guided to an incorrect destination in the distal stump;
for example, cutaneous fibers may enter motor endoneurial tubes and vice versa.
Figure 3-48 Photomicrographs of motor neurons of the anterior gray column of the spinal cord. A: Nissl substance in normal neurons. B: Following section of anterior roots of spinal nerve, showing chromatolysis.
5. Inadequate physiotherapy to the paralyzed muscles w ill result in their degeneration before the regenerating motor axons have reached them.
6. The presence of infection at the site of the w ound w ill seriously interfere w ith the process of regeneration.
If one assumes that the proximal and distal stumps of the severed nerve are in close apposition, the follow ing
regenerative processes take place (Fig. 3-47). The Schw ann cells, having undergone mitotic division, now fill the space w ithin the basal lamina of the endoneurial tubes of the proximal stump as far proximally as the next node of Ranvier and in the distal stump as far distally as the end-organs. Where a small gap exists betw een the proximal and distal stumps, the multiplying Schw ann cells form a number of cords to bridge the gap.
Figure 3-49 The changes that may take place in a nerve cell body following division of one of its processes.
Each proximal axon end now gives rise to multiple fine sprouts or filaments w ith bulbous tips. These filaments, as they grow , advance along the clefts betw een the Schw ann cells and thus cross the interval betw een the proximal and distal nerve stumps. Many such filaments now enter the proximal end of each endoneurial tube and grow distally in contact w ith the Schw ann cells (Fig. 3-50). It is clear that the filaments from many different axons may enter a single
endoneurial tube. How ever, only one filament persists, the remainder degenerate, and that one filament grow s distally to reinnervate a motor or sensory end-organ. While crossing the gap betw een the severed nerve ends, many
filaments fail to enter an endoneurial tube and grow out into the surrounding connective tissue. It is interesting to note that the formation of multiple sprouts or filaments from a single proximal axon greatly increases the chances that a neuron w ill become connected to a sensory or motor ending. It is not know n w hy one filament w ithin a single
endoneurial tube should be selected to persist w hile the remainder degenerate.
Once the axon has reached the end-organ, the adjacent Schw ann cells start to lay dow n a myelin sheath. This process begins at the site of the original lesion and extends in a distal direction. By this means, the nodes of Ranvier and the Schmidt-Lanterman incisures are formed.
Figure 3-50 Photomicrograph of a longitudinal section of the distal stump of the sciatic nerve showing evidence of degeneration and axon regeneration following injury. (Courtesy Dr. M . J. T. Fitzgerald.)
Many months may elapse before the axon reaches its appropriate end-organ, depending on the site of the nerve injury. The rate of grow th has been estimated to be approximately 2 to 4 mm per day. If, how ever, one takes into consideration the almost certain delay incurred by the axons as they cross the site of the injury, an overall
regeneration rate of 1.5 mm per day is a useful figure to remember for clinical use. Even if all the difficulties outlined above are overcome and a given neuron reaches the original end-organ, the enlarging axonal filament w ithin the endoneurial tube reaches only about 80% of its original diameter. For this reason, the conduction velocity w ill not be as great as that of the original axon. Moreover, a given motor axon tends to innervate more muscle fibers than formerly; thus, the control of muscle is less precise.