Background. Spinal cord injury causes severe and often irreversible motor deficits, largely due to neuronal loss, impaired axonal regeneration, and dysregulation of neurotrophic signaling pathways. Neurotrophins such as neurotrophin-3/4 (NT-3/4), and glial cell line–derived neurotrophic factor (GDNF) play critical roles in neuronal survival, synaptic plasticity, and functional recovery following SCI. Additionally, rehabilitation through exercise-based and functional electrical stimulation (FES) have been shown to modulate neurotrophic factor expression and improve locomotor outcomes after SCI; however, the molecular effects of their combined application remain poorly understood.
Objectives. Here we aimed to investigate the combined effects of aerobic exercise and functional electrical stimulation on NT-3, NT-4, and GDNF gene expression and locomotor recovery in a rat model of spinal cord injury.
Methods. Utilizing thirty-three adult male Wistar rats that were randomly assigned to five groups of healthy control, SCI control, SCI with exercise, SCI with FES, and SCI with combined exercise and FES, SCI induction was performed at the T11 vertebral level, where animals in the intervention groups underwent seven days of treadmill-based aerobic training and/or spinal electrical stimulation. The Basso, Beattie, and Bresnahan (BBB) scale was used to assess locomotor recovery. Gene expression levels of NT-3, NT-4, and GDNF were investigated using qRT-PCR. The results were then analyzed statistically using one-way ANOVA and Tukey's post-hoc test (p<0.05).
Results. The improvement in the locomotor function of FES group at week 2 post-injury was statistically significant, although aerobic exercise demonstrated effectiveness from week 4 onward. Notably, the combined exercise and FES treatment, resulted in the most substantial improvements. Significant upregulation of NT-3, NT-4, and GDNF was evident in the gene expression analysis of the combined intervention group compared to other groups (p<0.01), where FES alone showed significant increases in gene expression compared to the SCI control group (p<0.05).
Conclusion. The findings suggest that the combined administration of FES and aerobic exercises enhances the motor recovery results in upregulates the expression of neurotrophic factors in SCI rats, holding promises as a therapeutic strategy for SCI rehabilitation.
Type of Study:
Original Article |
Subject:
Sport Physiology and its related branches Received: 2025/11/21 | Accepted: 2027/01/12
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