Protective effects of low-intensity pulsed ultrasound (LIPUS) against cerebral ischemic stroke in mice by promoting brain vascular remodeling via the inhibition of ROCK1/p-MLC2 signaling pathway
Rong Chen, Wei Du, Xiao Zhang, Renhao Xu, Wei Jiang, Cong Zhang, Yi Yang, Huiran Zhang, Xiaoli Xie, Degang Song, Yi Yuan, Xiangjian Zhang
Cerebral Cortex 2023 · 10.1093/cercor/bhad330
Abstract
Vascular remodeling is essential for patients with cerebral ischemic stroke (CIS). Our previous study proved that low-intensity pulsed ultrasound (LIPUS) could increase cortical hemodynamics. However, the effects and mechanisms of LIPUS on cerebral vascular remodeling after CIS are still unknown. In this study, we applied LIPUS to the mouse brain at 0.5 h after distal middle cerebral artery occlusion (dMCAO) and subsequently daily for a stimulation time of 30 min. Results showed that compared with the dMCAO group, LIPUS markedly increased cerebral blood flow (CBF), reduced brain swelling, and improved functional recovery at day 3 after CIS. LIPUS promoted leptomeningeal vasculature remodeling, enlarged vascular diameter, and increased the average vessel length and density at day 3 after CIS. Proteomic analysis highlighted that LIPUS mainly participated in the regulation of actin cytoskeleton pathway. Rho kinase 1 (ROCK1) was downregulated by LIPUS and participated in regulation of actin cytoskeleton. Subsequently, we verified that ROCK1 was mainly expressed in pericytes. Furthermore, we demonstrated that LIPUS inhibited ROCK1/p-MLC2 signaling pathway after CIS, which had positive effects on vascular remodeling and cerebral blood circulation. In conclusion, our preliminary study revealed the vascular remodeling effects and mechanism of LIPUS in CIS, provided evidence for potential clinical application of LIPUS.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS after dMCAO (and in sham-operated mice)
Target: brain — “the top of the head of mice”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 50 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 | |
| Pressure, domain unspecified (kPa) | 530 | ✓✓✓⚑ |
LIPUS applied at 0.5 h after dMCAO and subsequently daily for a stimulation time of 30 min until the mouse was sacrificed; fundamental frequency 1 MHz, stimulation duration 5 min, PRF 1 Hz, duty cycle 5%.
Flags from extraction
n_subjects— Four groups of 93 (n value printed as 'n 93', equals sign missing); LIPUS-treated groups are Sham LIPUS and dMCAO LIPUS; total exposed not stated.exposures[0].timing.sonication_duration_s— Text says 'stimulation time of 30 min' daily and also 'stimulation duration ... 5 min'; the 5 min value is recorded, conflict unresolved.exposures[0].unspecified_domain.pressure_kpa— 'The ultrasound pressure was 0.53 MPa and corresponding spatial peak'; domain and pressure type not stated.exposures[0].timing.pulse_duration_ms— Pulse duration not stated.exposures[0].target.terms— Transducer placed on the top of the head; no specific brain region named.sham_type— Control group received no ultrasound stimulation; whether transducer was placed is not stated.