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低强度脉冲超声调节肌萎缩侧索硬化症 SOD1 小鼠模型中的疾病进展。

Low-intensity pulsed ultrasound modulates disease progression in the SOD1 mouse model of amyotrophic lateral sclerosis.

机构信息

Department of Ultrasonography, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai 200233, China.

Department of Neurology, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai 200233, China.

出版信息

Cell Rep. 2024 Sep 24;43(9):114660. doi: 10.1016/j.celrep.2024.114660. Epub 2024 Aug 22.

DOI:10.1016/j.celrep.2024.114660
PMID:39180748
Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1 mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.

摘要

肌萎缩侧索硬化症(ALS)是一种破坏性的神经退行性疾病,其特征是大脑和脊髓中的运动神经元逐渐丧失,目前尚无有效的药物治疗方法。低强度脉冲超声(LIPUS)作为一种有前途的非侵入性神经调节方法引起了人们的关注。在这项研究中,我们使用 SOD1 肌萎缩侧索硬化症小鼠模型研究了它对运动皮层的影响及其潜在机制。我们的结果表明,LIPUS 治疗可延迟疾病发作并延长 ALS 小鼠的寿命。LIPUS 通过保持血管内皮细胞完整性和增加微血管密度来显著增加运动皮层的脑血流量,这可能是通过离子通道 TRPV4 介导的。RNA 测序分析表明,LIPUS 可显著降低与神经炎症相关基因的表达。这些发现表明,应用于运动皮层的 LIPUS 可能代表治疗 ALS 的一种潜在有效治疗工具。

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