中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2275-2294.doi: 10.4103/NRR.NRR-D-25-00113

• 综述:退行性病与再生 • 上一篇    下一篇

低强度经颅超声神经调控技术促进神经元再生：无创治疗神经退行性疾病的新希望

  

  • 出版日期:2026-06-15 发布日期:2025-09-17
  • 基金资助:
    STI2030重大项目（2021ZD0204200）

Low-intensity transcranial ultrasound neuromodulation promotes neuronal regeneration: A new hope for noninvasive treatment of neurodegenerative diseases

Shu Xia1, #, Chen He2, #, Yunfei Li3, 4, Hao Li2 , Bo Wang3, 5, 6, 7, Long Xu2, 8, *, Xudong Zhao5, 6, 7, *   

  1. 1 Kangda College, Nanjing Medical University, Lianyungang, Jiangsu Province, China;  2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;  3 Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui Province, China;  4 Institute of Advanced Technology, University of Science and Technology of China, Hefei, Anhui Province, China;  5 State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;  6 CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing, China;  7 University of Chinese Academy of Sciences, Beijing, China; 8 China National Clinical Research Center for Neurological Diseases, Beijing, China
  • Online:2026-06-15 Published:2025-09-17
  • Contact: Long Xu, MD, neurotrauma@vip.163.com; Xudong Zhao, PhD, zhaoxudong@ibp.ac.cn.
  • Supported by:
    This work was supported by STI2030-Major Project, No, 2021ZD0204200 (to LX).

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摘要：

神经退行性疾病以渐进性神经元缺失和缺乏改变疾病的疗法为特征，正成为全球健康的一大挑战。目前的神经调控技术，如脑深部刺激和经颅磁刺激，由于侵入性、有限的皮质靶向性和不可逆的组织效应等问题而受到限制。低强度经颅超声是一种非侵入性方法，可深入大脑并调节神经可塑性，已成为一种潜在的替代方法。此综述的目的是全面评估低强度经颅超声在神经退行性疾病中的治疗机制、疗效和转化潜力，重点关注其在促进神经元再生、调节神经炎症和增强功能恢复方面的作用。我们总结了以往的研究，系统阐述了低强度经颅超声在调节细胞死亡机制、促进神经修复和再生以及缓解神经退行性疾病症状方面的潜力。临床前研究结果表明，低强度经颅超声可以促进神经营养因子（如脑源性神经生长因子）的释放，增强自噬作用以清除蛋白质聚集，调节小胶质细胞的活化，并暂时打开血脑屏障以进行靶向给药。现有的临床试验数据显示，低强度经颅超声可减少淀粉样β斑块，改善运动和认知障碍，并促进疾病模型中的髓鞘再形成。早期临床试验表明，低强度经颅超声可以提高阿尔茨海默氏症患者的认知能力，减轻帕金森病患者的运动症状，而且安全性良好。以往研究表明，低强度经颅超声集安全性、精确性和可逆性于一身，有可能改变神经退行性疾病的治疗方法。然而，低强度经颅超声未来的临床应用还需要改进，例如优化参数（频率、强度、占空比），考虑个体之间的解剖差异，以及确认长期疗效。由此认为，低强度经颅超声关键是要建立标准化方案、开展更大规模的试验、研究机制以明确剂量-反应关系并完善个性化应用策略。未来研究的重点应该是将临床前研究成果转化为临床应用，解决技术难题，并探索与药物或基因干预相结合的疗法。

https://orcid.org/0000-0002-3369-5588 (Long Xu); https://orcid.org/0009-0000-6961-3292 (Xudong Zhao)

关键词: 阿尔茨海默病, 额颞叶痴呆, 低强度经颅超声, 多系统萎缩, 多发性硬化, 神经退行性疾病, 神经元再生, 神经调节, 帕金森病, 经颅超声刺激

Abstract: Neurodegenerative diseases, which are characterized by progressive neuronal loss and the lack of disease-modifying therapies, are becoming a major global health challenge. The existing neuromodulation techniques, such as deep brain stimulation and transcranial magnetic stimulation, show limitations such as invasiveness, restricted cortical targeting, and irreversible tissue effects. In this context, low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity. This review comprehensively assesses the therapeutic mechanisms, efficacy, and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases, with emphasis on its role in promoting neuronal regeneration, modulating neuroinflammation, and enhancing functional recovery. We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms, enhancing neural repair and regeneration, and alleviating symptoms associated with neurodegenerative diseases. Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors (e.g., brainderived neurotrophic factor), promote autophagy to clear protein aggregates, modulate microglial activation, and temporarily open the blood–brain barrier to facilitate targeted drug delivery. Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-β plaques, improve motor and cognitive deficits, and promote remyelination in various disease models. Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease, all while demonstrating a favorable safety profile. Past studies support the notion that by integrating safety, precision, and reversibility, low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease. However, more advancements are necessary for future clinical application of low-intensity transcranial ultrasound, including optimizing parameters such as frequency, intensity, and duty cycle; considering individual anatomical differences; and confirming long-term efficacy. We believe establishing standardized protocols, conducting larger trials, and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard. Future research should focus on translating preclinical findings into clinical practice, addressing technical challenges, and exploring combination therapies with pharmacological or gene interventions.

Key words: Alzheimer’s disease, frontotemporal dementia, low-intensity transcranial ultrasound, multiple sclerosis, multiple system atrophy, neurodegenerative diseases, neuromodulation, neuronal regeneration, Parkinson’s disease, transcranial ultrasound stimulation