The fate of the neuromuscular junction in peripheral nerve injury – current understanding and future research aims: A scoping review

Importance Peripheral nerve injury (PNI) represents a challenging frontier for the many surgical specialties dealing with these injuries. Improved surgical techniques and understanding have resulted in improvements in patient care, but a mastery of the processes of nerve regeneration and repair have proved elusive. Objective This review intends to outline the changes at the neuromuscular junction in response to denervation injury. By reviewing the current literature, we aim to solidify the understanding of these morphological changes and identify future areas of research need. Review A literature search of PubMed, Embase and Web of Science including studies up to 22 nd December 2023 was carried out. Search terms related to the motor endplate or neuromuscular junction, nerve degeneration, peripheral nerve injury and nerve regeneration. Three researchers independently performed screening of potentially relevant studies, using Covidence (Melbourne, Australia), a review workflow platform facilitating blinded reviewing. Results are reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines Findings We identified 3595 records in the initial search, with no additional articles identified through backward and forward citation tracking. 350 full-text reports were assessed for eligibility. Ultimately, 118 studies were included for data extraction. Conclusions and Relevance The mechanisms of degeneration and regeneration at the NMJ summarised within provide multiple opportunities for ongoing research. Terminal Schwann cells and the constituents of the post synaptic apparatus may be able to be induced to survive for longer, or to be replenished to levels facilitating functional recovery from greater periods of denervation.