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

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-02-01 DOI:10.1016/j.lfs.2024.123341

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

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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.

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经颅交流电刺激通过cGMP-PKG信号通路抑制铁下垂并促进脊髓损伤的功能恢复。

目的：本研究探讨神经调节，特别是经颅交流电刺激（tACS）作为脊髓损伤（SCI）康复治疗的潜力。主要方法：通过精心优化治疗参数和持续时间，我们的目标是增强神经再生和促进功能恢复。为了评估tACS的疗效，我们的实验采用大鼠T10脊髓损伤模型。运动功能结果采用Basso-Beattie-Bresnahan （BBB）评分量表和足迹分析进行测量。为了彻底了解tACS的影响，我们在损伤后两周进行了一系列组织学评估。其中包括q-PCR，酶联免疫吸附测定（ELISA），透射电子显微镜（TEM），免疫荧光染色和Western blotting。本文将通过综合分析阐明tACS作用的机制。主要发现：同时，tACS降低了脊髓损伤后的活性氧（ROS）、铁（Fe）和丙二醛（MDH）水平，并增加了谷胱甘肽（GSH）水平。此外，tACS显著增强运动功能，减少纤维化瘢痕组织的形成，并提供大量的神经保护。它还有助于血脊髓屏障的恢复，并支持必要神经成分的再生，包括轴突、髓磷脂和突触。cGMP-PKG信号通路在这些过程中起着至关重要的作用。意义：我们的研究结果表明，tACS通过调节cGMP-PKG信号通路抑制铁下垂和坏死性变性。这凸显了tACS在促进脊髓损伤患者神经修复和功能恢复中的重要性。综上所述，tACS是一种高效、经济的脊髓损伤康复方法，为改善患者预后带来了新的希望。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.