Transcranial Alternating Current Stimulation Inhibits Ferroptosis and Promotes Functional Recovery in Spinal Cord Injury via the cGMP-PKG Signaling Pathway

You Huangjun, Sun Weiming, Huang Ke, Shuai Lang, Bi Haidi
Purpose:

This study explores the potential of neuromodulation, specifically transcranial alternating current stimulation (tACS), as a promising rehabilitative therapy in spinal cord injury (SCI).

Methods:

By meticulously optimizing treatment parameters and durations, our objective was to enhance nerve regeneration and facilitate functional recovery. To assess the efficacy of tACS, our experiments used the rat T10 spinal cord injury model. Motor function outcomes were measured using the Basso-Beattie-Bresnahan (BBB) scoring scale and footprint analysis. To thoroughly understand the impact of tACS, we conducted an array of histological evaluations two weeks post-injury. These included Quantitative Reverse Transcription Polymerase Chain Reaction(q-PCR), enzyme-linked immunosorbent assays (ELISA), transmission electron microscopy (TEM), immunofluorescence staining, and Western blotting. The mechanisms underlying the role of tACS will be elucidated through comprehensive analyses.


Results:

Our findings indicate that tACS inhibits ferroptosis while significantly enhances motor function, reduces fibrotic scar tissue formation, and offers substantial neuroprotection. Furthermore, tACS contributes to the restoration of the blood-spinal cord barrier and supports the regeneration of essential neural components, including axons, myelin, and synapses. At the same time, tACS reduced the levels of reactive oxygen species (ROS), Fe, and malondialdehyde (MDH), and increased the levels of glutathione (GSH) after SCI. Notably, the cGMP-PKG signaling pathway plays a critical role in these processes.



Conclusion(s):

Proteomic analyses showed that tACS is vital in inhibiting neuronal ferroptosis and necrotic degeneration through modulation of the cGMP-PKG signaling pathway. Overall, tACS emerges as a highly effective and cost-efficient rehabilitative approach for spinal cord injury.

Implications:

An innovative therapeutic strategy for patients with SCI that modulates the cGMP-PKG signalling pathway through tACS to effectively inhibit iron death and promote functional recovery. This study expands the understanding of the treatment of SCI, breaks through the limitations of traditional therapeutic approaches, and provides more therapeutic options for patients. In addition, the implementation of this strategy can help promote the development of rehabilitation medical services and improve the rehabilitation outcome and quality of life of spinal cord injury patients. With these advances, we look forward to creating a better future for our patients.

Funding acknowledgements:
This study was supported by the National Natural Science Foundation of China (No. 82160441)
Keywords:
Spinal Cord Injuries
Transcranial alternating current stimulation
cGMP-PKG Signalling Pathway
Primary topic:
Basic science including molecular and cellular health
Second topic:
Disability and rehabilitation
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
This study was approved by the Animal Research Committee of the First Affiliated Hospital of Nanchang University
Provide the ethics approval number:
Approval No. CDYFY-IACUC 202211 QR 007
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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