Efficacy of Low-Intensity Transcranial Ultrasound Stimulation in Enhancing Motor Recovery via Modulation of Microglial Polarization, Angiogenesis and Neurogenesis in MCAO Rats
Mingjun He, Peishan Wu, Xiaojing Long, Chao Shi, Xinhan Cao, Xingchen Huang, Yongjie Zhu, Ruli Li, De Meng, Aidong Li, Chunfang Li, Li Luo, Hongmei Wen, Yao Wang
Ultrasound in Medicine & Biology 2025 · 10.1016/j.ultrasmedbio.2025.05.031
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.
Abstract via europepmc.
Exposures
Exposure 1: MCAO + LITUS
Target: brain — “cranium”
Device: other named manufacturer · GreenValley BrainTech (Shenzhen) Medical Technology Co., Ltd · GVBT-1-A001 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 930 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 7.7 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.77 | ✓✓✓ |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.462 | ✓✓✓ |
Pulsed 1 MHz, tone burst 200 us, duty cycle 20%, 1-s stimulus repeated every 2 s; 30 min daily for six consecutive days starting 24 h after MCAO.
Consistency checks: intensity pressure inconsistent free field.
Flags from extraction
exposures[0].free_field— Pressure and intensity said to be 'measured' at the focus without stating water; placed in free_field on that reading.exposures[0].in_situ.method— Effective Ispta 462 mW/cm2 from hydrophone measurement of 40% attenuation through skulls; recorded as measurement.blinding— Only outcome observers were blinded for imaging quantification; recorded as single.exposures[0].timing.pulse_repetition_frequency_hz— PRF not stated.exposures[0].target.terms— No anatomical target named; transducer coupled to the cranium, focal zone at 8 mm depth.sham_type— MCAO group received no ultrasound and no sham procedure is described; Control group had no surgery.