Zhang Min, Zhao Liang, Silveira Paulo Cesar Lock
College of Sports and Health, Shandong Sport University, Jinan 250102, China.
Office of Human Resources, Shandong Sport University, Jinan 250102, China.
Biology (Basel). 2025 Aug 30;14(9):1148. doi: 10.3390/biology14091148.
The repeated head impacts experienced by athletes have attracted significant interest from both the public and the scientific community; however, the neurobiological effects following the games are not well understood. For example, a single football match carries the risk of repeated concussive and subconcussive head impacts, which can increase the risk of developing neurodegenerative diseases. Chronic traumatic encephalopathy (CTE) is one of the neurodegenerative conditions athletes often face or are unaware of. However, addressing the disease progression in CTE is difficult to determine due to several reasons, such as the failure to identify risk factors, difficulty in differentiating CTE from other neurodegenerative diseases, and the lack of a specific mechanism by which CTE leads to tau protein accumulation. In addition, CTE symptoms overlap with other neurodegenerative conditions, such as Alzheimer's disease (AD) and Parkinson's disease (PD), which poses a challenge to producing specific targeted therapy. In this case, ultrasound represents a promising non-invasive technique that enables clear visualization of brain structures and may modulate neuronal activity. The term ultrasound encompasses various modalities; for example, high-intensity focused ultrasound (HIFU) employs thermal energy to ablate cells, whereas low-intensity pulsed ultrasound (LIPUS) delivers mechanical energy that activates molecular signaling pathways to impede the progression of CTE. Therefore, the LIPUS application could potentially minimize the risk of damage in the surrounding tissues of the brain and reduce the disease progression in individuals with CTE. Nevertheless, limited studies have been reported in the literature, with a poor mechanistic approach. Hence, this review aims to highlight the molecular signaling pathways, such as AKT, MAPK, and ERK, affected by LIPUS and emphasize the need for additional research to clarify its mechanistic effects in CTE management. Ultimately, this review aims to contribute to a nuanced understanding of LIPUS as a therapeutic strategy in addressing the complexities of CTE and its associated neurodegenerative disorders.
运动员反复遭受头部撞击已引起公众和科学界的极大关注；然而，比赛后神经生物学效应尚未得到充分了解。例如，一场足球比赛就存在反复发生震荡性和亚震荡性头部撞击的风险，这会增加患神经退行性疾病的风险。慢性创伤性脑病（CTE）是运动员经常面临或未意识到的神经退行性疾病之一。然而，由于多种原因，很难确定CTE的疾病进展，比如无法识别风险因素、难以将CTE与其他神经退行性疾病区分开来，以及缺乏CTE导致tau蛋白积累的具体机制。此外，CTE症状与其他神经退行性疾病（如阿尔茨海默病（AD）和帕金森病（PD））重叠，这对开发特定的靶向治疗构成了挑战。在这种情况下，超声是一种很有前景的非侵入性技术，能够清晰显示脑结构，并可能调节神经元活动。超声这个术语涵盖多种模式；例如，高强度聚焦超声（HIFU）利用热能消融细胞，而低强度脉冲超声（LIPUS）传递机械能，激活分子信号通路以阻止CTE的进展。因此，LIPUS的应用有可能将脑周围组织受损的风险降至最低，并减缓CTE患者的疾病进展。然而，文献中报道的研究有限，且缺乏对机制的深入探讨。因此，本综述旨在强调受LIPUS影响的分子信号通路，如AKT、MAPK和ERK，并强调需要进行更多研究以阐明其在CTE管理中的机制作用。最终，本综述旨在有助于更细致地理解LIPUS作为一种治疗策略在应对CTE及其相关神经退行性疾病复杂性方面的作用。
