Transcranial Intermittent Theta-Burst Stimulation Reverses Neurodegeneration in the Somatosensory Motor Cortex after Spinal Cord Transection in Rats

Background: Complete spinal cord injury (SCI) leads to a disconnection between the brain and the body below the injury level, resulting in the functional silencing, degeneration, and apoptosis of sensorimotor cortex (SMC) neurons, which is of crucial importance to the pathological process.Methods: In this study, a rat model of spinal cord transection was employed to explore the activation of neurons in the SMC and the reversal of neurodegeneration after the rats were treated with transcranial intermittent theta-burst stimulation (T-iTBS).Results: The results demonstrated that the expression of the immediate early gene c-Fos and the synaptic plasticity-associated activity-regulated cytoskeleton (Arc) gene in the neurons of the SMC was increased in the T-iTBS group 4 weeks after SCI. Transcriptome sequencing revealed that neuronal activation-, neuronal metabolism-, synaptic activity-, and neural regeneration-related genes were significantly upregulated in the T-iTBS group compared with those of the sham-iTBS group, but the expression was similar to that in the normal group. Western blot analysis indicated that the expression of Cle-caspase-3 (CC3) in the SMC was significantly reduced in the T-iTBS group, and the number of CD68-positive cells in the SMC was close to that of normal rats but significantly less than that in the sham-iTBS and SCI groups. These results are in line with those of the transcriptome sequencing. Correlation analysis of the expression rate between c-Fos and Arc, CC3, and CD68 further suggested that T-iTBS improved the immune microenvironment and prevented neurodegeneration by regulating the activation and synaptic plasticity of SMC neurons in the early stages of injury.Conclusions: Collectively, our findings offer support for the utilization of T-iTBS, a non-invasive neural stimulation treatment, to prevent SMC degeneration following severe SCI.