Improving Nerve and Muscle Function: An Exploration of Targeted Nerve Function Replacement Following Differential Delay Periods in a Rat Model

Background Targeted Muscle Reinnervation (TMR) improves real-time control of EMG-based prostheses by connecting severed nerves to adjacent muscles, creating new EMG signals. However, TMR requires cutting original nerve connections, which can cause denervation atrophy and limit functional recovery. As an alternative, Targeted Nerve Function Replacement (TNFR) offers promising potential for limb function restoration. This study evaluates TNFR efficacy in restoring denervated muscle function across different postoperative intervals in a rat model. Methods Thirty Sprague-Dawley rats (220–250 g) were divided into five equal groups (n = 6 per group): control (no transection), denervation (transection without repair), immediate TNFR after median nerve transection, 2-week delayed TNFR, and 4-week delayed TNFR. The median nerve was selected for reinnervation with the musculocutaneous nerve innervating the brachialis muscle serving as the anastomosis target. All assessments were conducted 4 weeks post-TNFR intervention, including intramuscular bipolar EMG recordings (1024 Hz sampling rate), behavioral assessment, muscle tension measurement, dorsal root ganglia (DRG) histology, and spinal cord motor neuron evaluation. Results Our findings revealed that immediate TNFR significantly outperformed delayed interventions across all measured parameters. EMG amplitude and root mean square values were significantly higher in the immediate TNFR group compared to delayed intervention groups (P < 0.05). Similarly, maximum contraction force and maximum tetanic contraction force of the biceps brachii demonstrated significantly superior recovery in the immediate TNFR group versus delayed groups (P < 0.05). Histological examination confirmed significantly greater preservation of sensory neurons in the DRG following immediate TNFR compared to delayed interventions (P < 0.05). Immunofluorescence analysis showed that immediate TNFR better preserved synaptic protein expression (synaptophysin/SYN) in motor neurons of the spinal cord compared to delayed interventions, indicating enhanced preservation of motor neuron function. Notably, immediate TNFR prevented the autophagic behavior observed in rats with delayed or absent intervention, suggesting better neuropathic pain prevention. Conclusion Timing critically influences TNFR outcomes, with immediate intervention yielding optimal restoration of both motor and sensory functions. This study provides valuable insights for optimizing surgical strategies in peripheral nerve injury, with important implications for limb reconstruction, rehabilitation protocols, and prosthetic development.