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低强度经颅超声刺激通过调节大脑中动脉闭塞大鼠小胶质细胞极化、血管生成和神经发生促进运动功能恢复的疗效

Efficacy of Low-Intensity Transcranial Ultrasound Stimulation in Enhancing Motor Recovery via Modulation of Microglial Polarization, Angiogenesis and Neurogenesis in MCAO Rats.

作者信息

He Mingjun, Wu Peishan, Long Xiaojing, Shi Chao, Cao Xinhan, Huang Xingchen, Zhu Yongjie, Li Ruli, Meng De, Li Aidong, Li Chunfang, Luo Li, Wen Hongmei, Wang Yao

机构信息

Department of Rehabilitation Medicine, Shenzhen Dapeng New District Nan'ao People's Hospital, Shenzhen, China.

Research Center for Medical AI, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

出版信息

Ultrasound Med Biol. 2025 Nov;51(11):1915-1924. doi: 10.1016/j.ultrasmedbio.2025.05.031. Epub 2025 Aug 12.

DOI:10.1016/j.ultrasmedbio.2025.05.031
PMID:40796499
Abstract

OBJECTIVE

Low-intensity transcranial ultrasound stimulation (LITUS) is a novel neuromodulation technology characterized by its non-invasive nature, strong penetration, and high spatial resolution, which has been applied in the treatment of neurological diseases. LITUS has demonstrated effectiveness in promoting motor function recovery following stroke; however, the underlying mechanisms remain unclear.

METHODS

A rat model of middle cerebral artery occlusion (MCAO) was established using the suture method, followed by a 6-day LITUS intervention initiated 24 h postmodel creation. The motor function of MCAO rats was evaluated using the open field test, catwalk gait analysis, and beam walking test. Additionally, a 9.4T animal MRI was employed to assess cerebral infarction volume and edema. Molecular biological changes related to microglial polarization, angiogenesis and neurogenesis were evaluated using enzyme-linked immunosorbent assay and immunofluorescence staining.

RESULTS

LITUS treatment significantly attenuated ischemic brain injury and improved motor dysfunction in MCAO rats. We observed that MCAO induced microglial activation and polarization in the ischemic brain cortex. Conversely, LITUS treatment inhibited microglial activation, suppressed M1 microglial polarization, and enhanced M2 microglial polarization. Furthermore, LITUS treatment promoted angiogenesis and neurogenesis in the brains of MCAO rats.

CONCLUSION

LITUS treatment effectively improves motor dysfunction in MCAO rats, potentially through the regulation of microglial polarization and the promotion of angiogenesis and neurogenesis. Therefore, LITUS may represent a promising therapeutic approach for addressing motor recovery associated with ischemic stroke.

摘要

目的

低强度经颅超声刺激(LITUS)是一种新型神经调节技术,具有无创、穿透力强和空间分辨率高的特点,已应用于神经疾病治疗。LITUS已证明在促进中风后运动功能恢复方面有效;然而,其潜在机制仍不清楚。

方法

采用缝合方法建立大脑中动脉闭塞(MCAO)大鼠模型,在造模后24小时开始进行为期6天的LITUS干预。使用旷场试验、猫步步态分析和横梁行走试验评估MCAO大鼠的运动功能。此外,采用9.4T动物MRI评估脑梗死体积和水肿。使用酶联免疫吸附测定和免疫荧光染色评估与小胶质细胞极化、血管生成和神经发生相关的分子生物学变化。

结果

LITUS治疗显著减轻了MCAO大鼠的缺血性脑损伤并改善了运动功能障碍。我们观察到MCAO诱导了缺血性脑皮质中小胶质细胞的激活和极化。相反,LITUS治疗抑制了小胶质细胞的激活,抑制了M1小胶质细胞极化,并增强了M2小胶质细胞极化。此外,LITUS治疗促进了MCAO大鼠大脑中的血管生成和神经发生。

结论

LITUS治疗有效改善了MCAO大鼠的运动功能障碍,可能是通过调节小胶质细胞极化以及促进血管生成和神经发生来实现的。因此,LITUS可能是一种有前景的治疗方法,用于解决与缺血性中风相关的运动恢复问题。

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