Effects of tail nerve electrical stimulation on the activation and plasticity of the lumbar locomotor circuits and the prevention of skeletal muscle atrophy after spinal cord transection in rats

Author:

Liu Jia‐Lin1ORCID,Chen Zheng‐Hong12ORCID,Wu Rong‐Jie134ORCID,Yu Hai‐Yang14ORCID,Yang Shang‐Bin15ORCID,Xu Jing156ORCID,Wu Chuang‐Ran14ORCID,Guo Yi‐Nan15ORCID,Hua Nan1ORCID,Zeng Xiang15ORCID,Ma Yuan‐Huan17ORCID,Li Ge18ORCID,Zhang Ling12ORCID,Chen Yuan‐Feng14ORCID,Zeng Yuan‐Shan1569ORCID,Ding Ying156ORCID,Lai Bi‐Qin1569ORCID

Affiliation:

1. Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat‐sen University), Ministry of Education Guangzhou Guangdong China

2. Rehabilitation Medicine Department The First Affiliated Hospital of Sun Yat‐sen University Guangzhou Guangdong China

3. Shantou University Medical College Shantou Guangdong China

4. Department of Orthopedics Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou Guangdong China

5. Department of Histology and Embryology Zhongshan School of Medicine, Sun Yat‐sen University Guangzhou Guangdong China

6. Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of Medicine, Sun Yat‐sen University Guangzhou Guangdong China

7. Guangzhou First People's Hospital, Guangzhou Institute of Clinical Medicine, South China University of Technology Guangzhou Guangdong China

8. Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences), Southern Medical University Guangzhou Guangdong China

9. Co‐innovation Center of Neuroregeneration Nantong University Nantong Jiangsu China

Abstract

AbstractIntroductionSevere spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological processes are significant obstacles for motor function reconstruction.ObjectiveWe performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function.MethodsEight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8.ResultsAfter 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles.ConclusionThe mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting‐edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs.

Funder

National Basic Research Program of China

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

Subject

Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology

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