Therapeutic effects of low-intensity transcranial ultrasound on neurological recovery in rat models of MCAO with varying injury severities

IF 2.6 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-08-06 DOI:10.1016/j.brainres.2025.149871

Yuyao Lai , Peishan Wu , Xinhan Cao , Mingjun He , Hongmei Wen , Li Luo , Xiaojing Long , Lijie Ren , Yao Wang

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Abstract

Background

Low-intensity transcranial ultrasound (LITUS) is a safe, non-invasive neuromodulation method shown to improve neurological function after ischemic stroke in middle cerebral artery occlusion (MCAO) rats models. Given that the degree of severity of ischemic damage may influence treatment outcomes, it is important to investigate the therapeutic performance of LITUS in various injury models to provide a comprehensive understanding to support its clinical application.

Methods

Sixty adult male SD rats were randomly divided into four groups: Sham (S), MCAO only (M), MCAO + high-intensity transcranial ultrasound (HITUS) injury + LITUS treatment (MHL), and MCAO + LITUS treatment (ML), with 15 rats per group. MCAO models were verified by 9.4 T MRI. LITUS was administered to MHL and ML groups for 20 min daily over 14 days. Behavioral tests, blood biomarkers, and molecular analyses (Western blot, qPCR, immunofluorescence) were used to evaluate neurological function, inflammation, and neurovascular changes.

Results

LITUS significantly improved neurological, motor, and cognitive functions in MCAO rats with varying injury severities. Treated animals showed better body weight recovery, lower Longa scores, improved motor coordination, and enhanced exploratory and recognition behavior. Mechanistically, LITUS reduced peripheral inflammation, downregulated iNOS expression, and regulated glucose, lipid, and homocysteine levels, supporting systemic homeostasis. It also promoted hematopoiesis and upregulated angiogenic markers (VEGF-A, eNOS, CD31), enhancing vascular regeneration in the ischemic cortex. Furthermore, LITUS activated the BDNF/nNOS signaling pathway, facilitating neurogenesis and neuronal repair. These findings suggest that LITUS exerts multi-target protective effects through coordinated regulation of inflammation, metabolism, angiogenesis, and neuroregeneration, offering strong therapeutic potential for stroke recovery.

Conclusion

LITUS treatment can improve neurological and motor dysfunction in MCAO rats with varying degrees of injury. The potential underlying mechanism of LITUS is through the regulation of the level of inflammation and promoting angiogenesis and neurogenesis.

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低强度经颅超声对不同损伤程度MCAO模型大鼠神经功能恢复的治疗作用。

背景：低强度经颅超声（LITUS）是一种安全、无创的神经调节方法，可改善大脑中动脉闭塞（MCAO）大鼠缺血性脑卒中后的神经功能。鉴于缺血性损伤的严重程度可能影响治疗效果，研究LITUS在各种损伤模型中的治疗效果，为其临床应用提供全面的了解是很重要的。方法：将60只成年雄性SD大鼠随机分为假手术(S)、单纯MCAO (M)、MCAO + 高强度经颅超声（HITUS）损伤 + LITUS治疗（MHL）和MCAO + LITUS治疗（ML） 4组，每组15只。采用9.4 T MRI对MCAO模型进行验证。MHL组和ML组每天给予LITUS 20 min，持续14 d。行为测试、血液生物标志物和分子分析（Western blot、qPCR、免疫荧光）用于评估神经功能、炎症和神经血管变化。结果：LITUS显著改善不同损伤程度MCAO大鼠的神经、运动和认知功能。治疗后的动物表现出更好的体重恢复，较低的Longa评分，改善的运动协调，增强的探索和识别行为。从机制上讲，LITUS减少外周炎症，下调iNOS表达，调节葡萄糖、脂质和同型半胱氨酸水平，支持系统稳态。它还促进造血和上调血管生成标志物（VEGF-A, eNOS, CD31），增强缺血皮质的血管再生。此外，LITUS激活BDNF/nNOS信号通路，促进神经发生和神经元修复。这些发现表明，LITUS通过协调调节炎症、代谢、血管生成和神经再生发挥多靶点的保护作用，对脑卒中恢复具有很强的治疗潜力。结论：LITUS治疗可改善不同程度MCAO大鼠的神经和运动功能障碍。LITUS的潜在机制是通过调节炎症水平和促进血管生成和神经发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.