Low-intensity pulsed ultrasound modulates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Zihao Liu, Huan Zhang, Kaili Lu, Li Chen, Yueqi Zhang, Zhouwei Xu, Hongsheng Zhou, Junfeng Sun, Mengyang Xu, Qi Ouyang, Garth J. Thompson, Yi Yang, Ni Su, Xiaojun Cai, Li Cao, Yuwu Zhao, Lixian Jiang, Yuanyi Zheng, Xiaojie Zhang
Cell Reports 2024, 43, 114660 · 10.1016/j.celrep.2024.114660
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 G93A 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.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to motor cortex in SOD1-G93A and wild-type mice
Target: motor cortex — “motor cortex”
Device: other named manufacturer · Shanghai Acoustics Laboratory ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 572 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 10 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 50 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 1,800 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.82 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
LIPUS therapy was performed for 30 min every two days for each mouse, using a wearable transducer positioned via a stereotactic system over a point in front of Bregma; Inter-Stimulus-Interval (ISI) = 1 s.
Exposure 2: LIPUS applied to SOD1-G93A-overexpressing brain endothelial cells (b.End.3) in vitro
Target: other — “cultured mouse brain endothelial cell line (b.End.3)”
Device: other named manufacturer · Shanghai Acoustics Laboratory ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 572 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 10 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 50 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 0.4 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
The same ultrasound device and centre frequency/PRF/duty-cycle/ISI as the in vivo experiments were used; each LIPUS intervention on b.End.3 cells lasted 5 min. Control cells were placed on the transducer for the same duration with the device turned off.
Flags from extraction
n_subjects— Reported as two non-overlapping group sizes (Tg-US N=31 SOD1-G93A mice; WT-US N=23 wild-type littermates) that both received LIPUS; given as a list per group rather than summed.n_sessions_per_subject— LIPUS was given 'every two days' from an unspecified start until variable disease-stage endpoints (mice were followed to onset/death, which varied by animal); no fixed total session count is stated.exposures[0].timing.pulse_duration_ms— PRF (50 Hz) and duty cycle (50%) are stated but pulse duration is not given directly in the text; not computed from PRF/duty cycle per protocol.exposures[1].timing.pulse_duration_ms— Same as exposures[0]: PRF and duty cycle stated, pulse duration not given directly.sham_type— Untreated control mice (Tg-NT, WT-NT) were only anaesthetised with no transducer or sham device applied; mechanism not otherwise described.