Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (3): 836-844.doi: 10.4103/NRR.NRR-D-23-01585

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Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Do-Hun Lee1, 2, 3, Dan Cao1, Younghye Moon3, Chen Chen1, 2, Nai-Kui Liu1, 2, Xiao-Ming Xu1, 2, †, Wei Wu1, 2, *   

  1. 1Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; 2Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; 3Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA †Deceased author
  • Online:2025-03-15 Published:2024-06-26
  • Contact: Wei Wu, MD, PhD, wu99@iu.edu.
  • Supported by:
    The work in the Wu laboratory was supported by the NIH (R01NS103481, R01NS111776, and R01NS131489) and Indiana Department of Health (ISDH58180) (all to WW).

Abstract: Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Key words: behavioral assessment, motor function, neural plasticity, running wheel exercise, spinal cord injury, treadmill exercise, voluntary exercise