Transcranial alternating current stimulation inhibits ferroptosis and promotes functional recovery in spinal cord injury via the cGMP-PKG signalling pathway

Ke Huang; Jing Fang; Shining Xiao; Wansong Wang; Guodong Zhang; Weiming Sun; Lang Shuai; Haidi Bi

doi:10.1016/j.lfs.2024.123341

Transcranial alternating current stimulation inhibits ferroptosis and promotes functional recovery in spinal cord injury via the cGMP-PKG signalling pathway

Life Sci. 2024 Dec 29:362:123341. doi: 10.1016/j.lfs.2024.123341. Online ahead of print.

Authors

Ke Huang¹, Jing Fang¹, Shining Xiao¹, Wansong Wang¹, Guodong Zhang¹, Weiming Sun², Lang Shuai³, Haidi Bi⁴

Affiliations

¹ Department of Rehabilitation Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; The First Clinical Medical College School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China.
² Department of Rehabilitation Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; The First Clinical Medical College School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. Electronic address: [email protected].
³ Department of Rehabilitation Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; The First Clinical Medical College School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: [email protected].
⁴ Department of Rehabilitation Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; The First Clinical Medical College School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Provincial Key Laboratory of Trauma, Burn and Pain Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: [email protected].

PMID: 39740757
DOI: 10.1016/j.lfs.2024.123341

Abstract

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

Main 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 SCI 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 a series of histological evaluations two weeks post-injury. These included 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.

Key findings: Simultaneously, tACS reduced the levels of reactive oxygen species (ROS), Fe, and malondialdehyde (MDH), and increased the levels of glutathione (GSH) after SCI. Additionally, tACS significantly enhanced motor function, reduced fibrotic scar tissue formation, and provided substantial neuroprotection. It also contributed to the restoration of the blood-spinal cord barrier and supported the regeneration of essential neural components, including axons, myelin, and synapses. The cGMP-PKG signalling pathway was identified as playing a crucial role in these processes.

Significance: Our findings suggest that tACS inhibits ferroptosis and necrotic degeneration by modulating the cGMP-PKG signalling pathway. This highlights the importance of tACS in promoting neural repair and functional recovery in SCI patients. Overall, tACS emerges as a highly effective and cost-efficient rehabilitative approach for SCI, offering new hope for improving patient outcomes.

Keywords: Axon regeneration; Neuronal ferroptosis; Spinal cord injuries; Transcranial alternating current stimulation; cGMP-PKG signalling pathway.