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Peer-reviewedCC BY 4.0Frontiers in Neuroscience

Transspinal temporal interference stimulation enhances neuroplasticity-associated responses and facilitates motor recovery after spinal cord injury in mice

  1. 1Clinical Medical College, Guizhou Medical University
  2. 2Department of Rehabilitation Medicine, Affiliated Hospital of Guizhou Medical University
  3. 3Department of Rehabilitation Medicine, Affiliated Hospital of Zunyi Medical University

Abstract

Introduction: Spinal cord injury (SCI) causes substantial motor impairment, driven by neuronal loss, axonal disruption, and impaired synaptic connectivity. Temporal interference (TI) stimulation is capable of modulating neural activity, but its therapeutic potential in SCI remains largely unexplored. We explored the influence of TI stimulation on functional recovery and neuroplasticity-associated responses following SCI.

Methods: Thirty-two C57BL/6J mice were randomly allocated to four groups: sham, SCI, sham stimulation, and TI stimulation. Mice underwent T8 spinal cord hemisection, followed by daily TI stimulation from day 4 to day 21 post-injury. Locomotor recovery was evaluated using the Basso Mouse Scale (BMS). At 21 days after injury, neuronal-associated changes, glial responses, and neuroplasticity-associated molecular changes were assessed by immunofluorescence staining and western blot analysis.

Results: Compared with sham-operated mice, SCI mice exhibited impaired locomotor function, reduced NeuN-positive neuronal density, and decreased expression of neuroplasticity-associated proteins, including GAP43, NF-L, SYN, and PSD95. In contrast, TI stimulation significantly improved BMS scores and increased NeuN-positive neuronal density, accompanied by enhanced expression of axonal growth-associated proteins (GAP43 and NF-L) and synaptic plasticity-associated markers (SYN and PSD95).

Discussion: These findings indicate that TI stimulation improves functional recovery after SCI and is associated with enhanced neuroplasticity-related responses, including axonal growth-associated and synaptic plasticity-associated changes. This study provides evidence supporting TI stimulation as a promising neuromodulation strategy for promoting neuroplasticity-associated recovery processes after spinal cord injury.

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BibTeX
@article{zheng2026transspinal,
  title = {{Transspinal temporal interference stimulation enhances neuroplasticity-associated responses and facilitates motor recovery after spinal cord injury in mice}},
  author = {Peng Zheng and Yan Chen and Yujiao Yue and Xianbin Wang and Shuang Wu},
  journal = {Frontiers in Neuroscience},
  year = {2026},
  month = oct,
  doi = {10.3389/fnins.2026.1950023},
  url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1950023/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Transspinal temporal interference stimulation enhances neuroplasticity-associated responses and facilitates motor recovery after spinal cord injury in mice
AU  - Peng Zheng
AU  - Yan Chen
AU  - Yujiao Yue
AU  - Xianbin Wang
AU  - Shuang Wu
PY  - 2026
DA  - 2026/10/06
JO  - Frontiers in Neuroscience
DO  - 10.3389/fnins.2026.1950023
UR  - https://www.frontiersin.org/articles/10.3389/fnins.2026.1950023/full
AB  - Introduction: Spinal cord injury (SCI) causes substantial motor impairment, driven by neuronal loss, axonal disruption, and impaired synaptic connectivity. Temporal interference (TI) stimulation is capable of modulating neural activity, but its therapeutic potential in SCI remains largely unexplored. We explored the influence of TI stimulation on functional recovery and neuroplasticity-associated responses following SCI.  Methods: Thirty-two C57BL/6J mice were randomly allocated to four groups: sham, SCI, sham stimulation, and TI stimulation. Mice underwent T8 spinal cord hemisection, followed by daily TI stimulation from day 4 to day 21 post-injury. Locomotor recovery was evaluated using the Basso Mouse Scale (BMS). At 21 days after injury, neuronal-associated changes, glial responses, and neuroplasticity-associated molecular changes were assessed by immunofluorescence staining and western blot analysis.  Results: Compared with sham-operated mice, SCI mice exhibited impaired locomotor function, reduced NeuN-positive neuronal density, and decreased expression of neuroplasticity-associated proteins, including GAP43, NF-L, SYN, and PSD95. In contrast, TI stimulation significantly improved BMS scores and increased NeuN-positive neuronal density, accompanied by enhanced expression of axonal growth-associated proteins (GAP43 and NF-L) and synaptic plasticity-associated markers (SYN and PSD95).  Discussion: These findings indicate that TI stimulation improves functional recovery after SCI and is associated with enhanced neuroplasticity-related responses, including axonal growth-associated and synaptic plasticity-associated changes. This study provides evidence supporting TI stimulation as a promising neuromodulation strategy for promoting neuroplasticity-associated recovery processes after spinal cord injury.
SN  - 1662-453X
SN  - 1662-4548
ER  -