Targeted muscle reinnervation surgery modulates apoptosis and synaptic plasticity to improve motor function following tibial nerve injury in rats

Targeted muscle reinnervation (TMR) is represents an advanced neural-machine interface that enhances prosthetic control and facilitates motor recovery in amputees. Although TMR is known to connect residual nerve fibers and supply neurotrophic factors, its impact on spinal cord motor neurons remains understudied. This study investigated the effects and possible mechanisms of TMR on spinal motor neurons in a rat model of tibial nerve transection (TNT).

There were 30 Sprague Dawley rats grouped into control, TNT, and TMR groups. TMR was grafted proximal tibial nerve into the gastrocnemius muscle. Outcome measures included the sciatic functional index, the muscle wet weight ratio, muscle fibrosis via Masson's trichrome staining, and immunohistochemical analysis of caspase-3 and Bcl-2 expression in spinal anterior horn. RT-PCR analysis of synaptic markers' mRNA expression.

The TNT group showed a marked SFI reduction, whereas the TMR group exhibited a significantly higher SFI (p < .01). Similarly, The operated muscle weight retention was preserved in the TMR relative to the TNT group (p < .01), indicating improved limb function and reduced atrophy. Masson trichrome staining demonstrated lower collagen deposition in the TMR group (p < .05). PCR analysis showed that TMR significantly downregulated spinal GAP43 mRNA (p < .05) while upregulating synapsin (SYN) and PSD-95 transcripts (both p < .05) versus TNT. Immunohistochemically, TMR decreased Bcl-2 (p < .05) and increased Caspase-3 (p < .01) expression relative to TNT.

These findings suggest that TMR promotes the spinal motor neuron recovery and synaptic remodelling, likely contributing to improve muscle morphology and overall post-injury functional outcomes.