Nerve-Muscle-Endplate Band Grafting

Abstract

Background As currently existing reinnervation methods result in poor functional recovery, there is a great need to develop new treatment strategies. Objectives To investigate the efficacy of our recently developed nerve-muscle-endplate band grafting (NMEG) technique for muscle reinnervation. Methods Twenty-five adult rats were used in this study. Sternohyoid (SH) and sternomastoid (SM) muscles served as a donor and a recipient muscle, respectively. Neural organization of the SH and SM muscles and surgical feasibility of the NMEG technique were determined. A NMEG contained a muscle block, a nerve branch with nerve terminals, and a motor endplate (MEP) band with numerous neuromuscular junctions. After a 3-month recovery period, the degree of functional recovery was evaluated using maximal tetanic force measurement. Retrograde horseradish peroxidase (HRP) tracing was used to track the origin of the motor innervation of the reinnervated muscles. The reinnervated muscles were examined morphohistologically and immunohistochemicaly to assess the extent of axonal regeneration. Results Nerve supply patterns and locations of the MEP bands in the SH and SM muscles were documented. The results demonstrated that the reinnervated SM muscles gained motor control from the SH motoneurons. NMEG technique yielded extensive axonal regeneration and significant recovery of SM muscle force generating capacity (67% of the control). The mean wet weight of the NMEG reinnervated muscles (87% of the control) was greater than that of the denervated SM muscles (36% of the control). Conclusion NMEG resulted in successful muscle reinnervation and functional recovery. This technique holds promise in the treatment of muscle paralysis.

Nerve growth factor and basic fibroblast growth factor promote reinnervation by nerve−muscle−endplate grafting

“…We have shown that the NMEG2NMZ technique resulted in better functional recovery (82% of the control) 11 when compared with our originally designed NMEG procedure (67% of the control). 9 The suboptimal functional outcome of our original NMEG procedure could be due, at least in part, to the fact that the NMEG pedicle was implanted into an aneural region in the target muscle. In this case, regenerating axons from the implanted NMEG pedicle may need more time to reach the most distal muscle fibers and form new MEPs.…”

“…The degree of functional recovery of the treated muscles was assessed by measuring the maximal tetanic force, as described in our previous publications. 9,11,[45][46][47][48][49] Briefly, the right treated and the left control SM muscles in each animal were exposed and dissected free from the surrounding tissues. The rostral tendon of each muscle was then divided at its insertion, tied with a 2-0 suture, and attached to a servomotor lever arm (Model 305B Dual-Mode Lever Arm System; Aurora Scientific, Inc., Aurora, Ontario, Canada).…”

“…At the moment of force measurement, the lever arm was stationary, and the muscle was adjusted to the optimal length by stretching the muscle with moderate tension of 0.08 N for the development of maximum force. 9,45 Muscle force of the right treated SM was measured by stimulating the SH nerve branch supplying the NMEG, whereas that of the left control muscle was measured by stimulating the intact SM nerve. Each of the nerves was isolated and draped over a bipolar stimulating electrode for nerve stimulation.…”

“…To facilitate MEP reinnervation to treat PNI-induced muscle paralysis, we developed a surgical method called "nerve-muscle-endplate band grafting" (NMEG) for muscle reinnervation in a rat model. 9 The NMEG reinnervation technique is based on the concept that a paralyzed muscle can be reinnervated by transplanting an NMEG from a neighboring donor muscle. A healthy nerve branch and terminals that innervate a non-essential muscle can be transplanted to a more functionally important denervated muscle for restoring its motor function.…”

“…Specifically, 3 months after implantation of the NMEG into an MEP-free area, the mean contractile force of the treated muscles was 67% of the controls. 9 In contrast, implantation of the NMEG into the native motor zone (NMZ) of the target muscle yielded better functional recovery (82%). 11 We hypothesized that the outcomes of NMEG2NMZ would be promoted by local application of neurotrophic factors to the implanted NMEG and NMZ of the target muscle to increase the rate of nerve regeneration and axon2MEP connections.…”