Remodeling of Neuromuscular Junctions in Target Muscle Following Nerve Regeneration in Mice After Delayed Peripheral Nerve Repair.

• Allogeneic nerve grafting led to more successful recovery than end-to-end neurorrhaphy after delayed peripheral nerve repair. • High numbers of Schwann cells are needed to promote NMJ reinnervation in the target muscle. • NMJ remodeling is related to agrin-Lrp4-MuSK signaling, Dok7 and Wnt4 during innervation. • Supplemental Schwann cells are important for delayed nerve repair. Peripheral nerve injury (PNI) induces severe functional loss in extremities. Progressive denervation and atrophy occur in the muscles if the nerve repair is delayed for long periods of the time. To overcome these difficulties, detailed mechanisms should be determined for neuromuscular junction (NMJ) degeneration in target muscles after PNI and regeneration after nerve repair. We established two models of end-to-end neurorrhaphy and allogeneic nerve grafting in the chronic phase after common peroneal nerve injury in female mice (n = 100 in total). We evaluated motor function, histology, and gene expression in the target muscles during their regeneration processes and compared the models. We found that the functional recovery with allogeneic nerve grafting was superior to that with end-to-end neurorrhaphy, and the number of reinnervated NMJs and Schwann cells was increased at 12 weeks after allograft. In addition, NMJ- and Schwann cell-related molecules showed high expression in the target muscle in the allograft model. These results suggest that Schwann cell migrating from the allograft might play a crucial role in nerve regeneration in the chronic phase after PNI. The relationship between the NMJ and Schwann cells should be further investigated in the target muscle. [ABSTRACT FROM AUTHOR]