Neurotization or the method of direct muscle reinnervation is the least studied, but at the same time, the most promising way to restore post-traumatic denervation. The application of the technique is justified when neurorrhaphy is not possible due to the absence or serious damage of the distal end of the nerve. In this case, autotransplantation and the use of conduits are impossible. For reinnervation in such cases, the proximal end of the nerve is directly implanted into the muscle tissue.
The first mention of successful neurotization refers to 1908 when the Hacker restored the motor function of the trapezius muscle of a 12-year-old patient. He implanted in the structure of this muscle the proximal segment of the accessory nerve along with the motor branch from the cervical plexus . However, despite the success, neurotization has not been used for a long time and has found application only in experimental studies on animals.
The problem of formation of new terminal plates or neuromuscular junctions (NMJ) attracts the greatest interest in this direction of neuroregeneration. The NMJ is the zone, in which the nervous system through the peripheral nerves interacts with the fibers of skeletal muscles and forces them to contractions. Damage to this NMJ mechanism causes many genetic diseases .
It is necessary to form the NMJ at the morphological level to realize electrophysiologic processes. Every branch of a distal end of the nerve have the postsynaptic folds, which increase the surface area of the postsynaptic membrane. There are vesicles containing neurotransmitters, which organize the intensity of nerve transmission through ion channels to the myocytes .
However, NMJ is formed not only with the formation of neuromuscular contact. Agrin binds to low-density lipoprotein, which is bound to the Lrp4 receptor. Thus, a muscle-specific kinase is activated in postsynaptic muscle fibers. At the same time, the presented chain of events is relevant not only for the formation of NMJ but also for its maintenance .
In summary, the key task of neurotization is the formation of new NMJs or the expansion/activation of the old NMJ zone after nerve implantation.
Controversial results of many experimental works were resolved in the technology of Sobotka and Mu . The authors of this study performed a dissection and coagulation of the nerve ends, innervating the left sternocleidomastoid muscle. On the opposite muscle, the distal part of the nerve trunk was resected with a site of innervated muscle tissue 6 mm × 6 mm × 3 mm in size to preserve the end plates. This neuromuscular block (NMB) was implanted by nerve suture with nylon 10/0.
Three months later, researchers stained the neurofilament with silver nitrate impregnation, and as a result, they noted that the regenerating axons from the implanted NMB sprouted into the recipient’s muscle. At the same time, the muscle mass was 87% of the control group, and the degree of functional restoration of the innervation was 66% when measuring the maximum contraction force.
Kang Sung-Bum with a group of researchers managed to restore the function of denervated muscle tissue through direct neurotization . Despite the success, the authors of the paper asked the same question of the absence of an appropriate nerve site for anastomosing and implantation. Indeed, many injuries lead to serious nerve damage with the formation of extended defects. Kang et al. refused to use the autograft of the nerve, fearing the characteristic complications for them . To solve the problem, the researchers applied a combined method: prolongation of the proximal nerve region with the help of a conduit for subsequent neurotization, as a material for conduit used silicone. After resection of the branches of the sciatic nerve from the innervated muscles, a conductor was placed in the resulting diastase. Its proximal end was sutured with a sciatic nerve, and the distal end was sutured with epimysium near the denervated terminal plate. The silicone conduit was filled with collagen gel. Control groups were completely denervated muscles.
In the course of the study, a stable contracture was observed in all control groups, except for the neurotization-conduit group. After 8 weeks in the experimental group, a weak contractile response to neurostimulation was observed, and by the end of the 20th week, the muscle response was close in strength and amplitude to normal. Histologically, in all control groups, fat infiltration and a decrease in the size of sarcomeres were observed; however, in the neurotization-conduit group, muscle fibers were restored, and the diameter of the axon increased. In conclusion, the authors of the study noted, that the presented combined technique can lead to a complete restoration of functions, but it is necessary to use a more sophisticated conduit and its inner environment .