Electroacupuncture at Dazhui (GV14) and Mingmen (GV4) acupoints promoting nerve repair in rat model of spinal cord injury: a study based on diffusion tensor imaging

Background: The rupture and demyelination of nerve fibers after spinal cord injury (SCI) are primary contributors to neurological dysfunction. The axon attraction signal pathway mediated by netrin-1 is crucial for promoting the effective regeneration and repair of nerve axons. Previous studies have proved that electroacupuncture (EA) can improve nerve function and promote nerve repair and regeneration in rats with SCI, yet its underlying mechanism remains to be elucidated. This study aims to evaluate the effects of EA on neural repair and to investigate its regulatory role in the axon guidance signaling pathway, thereby clarifying the mechanisms by which EA promotes nerve repair following SCI.

Methods: Male Sprague Dawley rats were randomly assigned to the Normal group, Sham group, SCI group, and EA group, with each group further divided into subgroups based on intervention duration: 7, 14, and 28 days. Allen’s method was employed to establish the SCI model. Dazhui (GV14) and Mingmen (GV4) acupoints were selected for EA intervention. Basso-Beattie-Bresnahan (BBB) score and the inclined plate test were used to evaluate the motor function of rats in each group. Morphological and structural changes in the injured spinal cord were assessed through magnetic resonance imaging (MRI). The fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) values in the injured area were measured via diffusion tensor imaging (DTI), and the morphological changes of nerve fiber bundles were analyzed via diffusion tensor tractography (DTT). The expressions of netrin-1, deleted in colorectal cancer (DCC), ras-related C3 botulinum toxin substrate 1 (Rac1) and F-actin were quantified using immunofluorescence (IF) staining, Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR).

Results: Compared with the Sham group, the SCI group exhibited significant deficits in motor function (P<0.01), disorganized spinal cord tissue structure, a markedly increased lesion area (P<0.01), impaired integrity of nerve fiber bundles, a significant decrease in FA value (P<0.01), and significantly elevated MD and RD values (P<0.01). Moreover, the expression levels of netrin-1, DCC, Rac1, and F-actin were significantly reduced (P<0.01). EA improved the behavioral performance of rats with SCI (P<0.01). Following EA intervention, the extent of spinal cord structural damage was alleviated, with increased FA values, decreased MD and RD values (P<0.01), alongside evident repair and reconstruction of damaged fiber bundles. Additionally, EA upregulated the expression levels of netrin-1, DCC, Rac1, and F-actin (P<0.01).

Conclusions: EA can significantly improve the motor function of rats with SCI, regulate the nerve guidance factor netrin-1 and its receptor DCC, as well as the molecular switch Rac1, thereby promoting axonal cytoskeletal remodeling and facilitating neural repair. The nerve repair effect of EA may be achieved by regulating the axon attraction signal pathway mediated by netrin-1.