Submission
| Title: |
Locomotor Exercise Enhances Supraspinal Control of Lower Urinary Tract Activity to Improve Micturition Function After Contusive Spinal Cord Injury |
| Co-Authors: |
Deng, Lingxiao, Indiana University School of Medicine; Tao Sui, 1Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Department of Neurological Surgery, Indiana University School of Medicine, Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Dong V Wang, Department of Neurobiology & Anatomy, Drexel University College of Medicine; Shaoping Hou, Department of Neurobiology & Anatomy, Drexel University College of Medicine; Xiaojian Cao, Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Kaiwen Peng, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Department of Neurological Surgery, Indiana University School of Medicine; Zaocheng Xu, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Department of Anatomy and Cell Biology, Indiana University School of Medicine; Xiaoming Xu, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Department of Neurological Surgery, Indiana University School of Medicine. |
Abstract
Background/Significance/Rationale: Locomotor training (LT) has been shown to improve micturition function. However, it is unknown whether this effect is attributable to the augmentation of supraspinal control of the external urethral sphincter (EUS).
Methods: We implemented a contusive SCI at the 12th thoracic level (T12) in rats and administered with forced wheel running exercise for 11 weeks. Awake rats then underwent bladder cystometrogram (CMG) and EUS electromyography recordings to examine the micturition reflex. Subsequently, pseudorabies virus (PRV) encoding red fluorescent protein were injected into the EUS to transsynaptically trace the supraspinal innervation of Onuf’s motoneurons.
Results/Findings: The results indicated that LT reduced the occurrence of bladder non-voiding contractions, decreased the voiding threshold and peak intravesical pressure, and shortened the latency of EUS bursting during voiding, leading to enhanced voiding efficiency. Histological analysis demonstrated that LT increased the extent of spared spinal cord tissue and the density of 5-HT+ axon terminals in the vicinity of Onuf’s motoneurons. More PRV-labeled or c-fos expressing neurons were detected in the brainstem, suggesting enhanced supraspinal control of EUS activity.
Conclusions/Discussion: LT promotes tissue sparing and supraspinal innervation of EUS motoneurons to improve LUT function following contusive SCI.
Translational/Human Health Impact: Urinary tract impairment has an enormous impact on life quality following SCI. LT is a less invasive and more tolerable intervention that has no adverse side effects. Yet the mechanism is unclear. Our results disclosed an unknown mechanism and provided important evidence for a rapid clinical translation.
