Neuroprotective Effect of Low-Intensity Pulsed Ultrasound on the Mouse MPTP/MPP+ Model of Dopaminergic Neuron Injury
Xueying Chen, Dong Wang, Liang Zhang, Huan Yao, Hui Zhu, Nvjun Zhao, Xiaoqiong Peng, Ke Yang
Ultrasound in Medicine & Biology 2021, 47, 2321-2330 · 10.1016/j.ultrasmedbio.2021.03.034
Abstract
Ultrasound mediated neuromodulation has been demonstrated to a safe treatment strategy in the field of neuroscience. In this study, low-intensity pulsed ultrasound (LIPUS) was used to treat Parkinson's disease (PD) models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP + ) to explore the possibility of ultrasound neuroprotective effect on PD. The results demonstrated that LIPUS treatment can attenuate the central neurotoxicity of MPTP in mice, reduce the loss of tyrosine hydroxylase positive neurons in the substantia nigra pars compacta and decrease the apoptosis in the section of substantia nigra. The movement and balance dysfunctions in PD mice were improved with LIPUS treatment. In addition, we demonstrated that LIPUS can inhibit the decreased activity and increased apoptosis of dopaminergic neurons induced by MPP + , restrain the accumulation of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential caused by MPP + . Moreover, LIPUS stimulation alone did not cause any cytotoxicity and tissue damage in our study. Taken together, the protective and regulatory effects of LIPUS on dopaminergic neurons make it possible as a new, safe and noninvasive treatment for PD.
Abstract via europepmc.
Exposures
Exposure 1: In vivo mouse head LIPUS irradiation (Grade 2 intensity), MPTP model
Target: whole brain or unfocused — “mouse head (non-focusing cylindrical transducer aligned to head), assessed effect on substantia nigra pars compacta dopaminergic neurons”
Device: other named manufacturer · Institute of Ultrasound Imaging of Chongqing Medical University · Ultrasound Gene Transfection Treatment Meter (UGT 1025) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 600 | ✓✓✓ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.111, 0.123swept | ✓✓✓ |
10 min of ultrasonic irradiation delivered once every 24 h for 5 sessions total, in mice receiving MPTP (or saline) 4 days before LIPUS onset.
Exposure 2: N2a cell culture LIPUS irradiation (Grade 1 intensity), MPP+ model
Target: other — “N2a cells (mouse neuroblastoma cell line) in culture”
Device: other named manufacturer · Institute of Ultrasound Imaging of Chongqing Medical University · Ultrasound Gene Transfection Treatment Meter (UGT 1025) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 20 | ✓✓✓ |
| Sonication duration (s) | 600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.0403, 0.0405swept | ✓✓✓ |
N2a cells were treated with LIPUS for 10 min, 4 h after MPP+ (0.75 mM) treatment; non-focusing cylindrical transducer placed under the culture plate.
Flags from extraction
n_subjects— Paper gives per-group n (5 animals/group, 4 groups); only the LIPUS-exposed groups (LIPUS-only and MPTP+LIPUS) are counted here as [5,5]; total not stated.exposures[0].unspecified_domain.isppa_w_cm2— Paper reports 'intensity of Grade 2' as measured by an ultrasound power meter without specifying whether this is ISPPA or ISPTA, and without specifying free-field vs in-situ domain.exposures[1].unspecified_domain.isppa_w_cm2— Same ambiguity as Grade 2 (ISPPA/ISPTA and domain not specified) for the Grade 1 intensity used on N2a cells.exposures[0].timing.pulse_duration_ms— PRF (1000 Hz) and duty cycle (20%) are stated but pulse duration is never given directly; computing it would require arithmetic on the stated values, so it is left not_reported.safety_notes— A separate, higher-intensity 'Grade 5' condition (~355-427 mW/cm2) caused death of mice by day 3; this was a preliminary safety observation, not part of the formally analysed Grade 1/2 exposures.exposures[1].in_situ— N2a cells were cultured in a well plate (dish) with no skull/tissue path; fields set to not_reported (rather than null) because the overall study also includes in vivo rodent exposures.