Ultrasonic stimulation of the brain to enhance the release of dopamine – A potential novel treatment for Parkinson’s disease
Tian Xu, Xiaoxiao Lu, Danhong Peng, Gongdao Wang, Chen Chen, Wen Liu, Wei Wu, Timothy J. Mason
Ultrasonics Sonochemistry 2020 · 10.1016/j.ultsonch.2019.104955
Abstract
Parkinson's disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm 2 - 0.3 W/cm 2 , 1 MHz), 12 h after exposure at 0.2 W/cm 2 , 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm 2 , 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents.
Abstract via europepmc.
Exposures
Exposure 1: Continuous-wave ultrasound applied to differentiated PC12 cells in dish
Target: other — “differentiated PC12 cells (dish culture)”
Device: other named manufacturer · Jiangsu Hanmei Science and Technology Co., Ltd. · HM-1 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 10, 20, 30, 40, 50, 60swept | ✓✓✓ |
| 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) | 0.1, 0.2, 0.3swept | ✓✓✓⚑ |
Cells were irradiated over various periods of time (10, 20, 30, 40, 50 and 60 s) at intensities of 0.1, 0.2 and 0.3 W/cm2; control samples were run in parallel without sonication. The headline dopamine-release result used 0.2 W/cm2 for 40 s, assessed 12 h after exposure.
Exposure 2: Transcranial ultrasound to head of MPTP-induced PD mice (non-focused)
Target: whole brain or unfocused — “shaved scalp/head (low intensity non-focused ultrasound aimed at brain, striatum/SNc dopamine assessed)”
Device: other named manufacturer · Jiangsu Hanmei Science and Technology Co., Ltd. · HM-1 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 300, 600, 900swept | ✓✓✓ |
| 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) | 0.1, 0.2, 0.3swept | ✓✓✓ |
An L9(3^3) orthogonal design varied intensity I (0.1/0.2/0.3 W/cm2), daily exposure time t (5/10/15 min) and treatment period T (1/5/10 days) across 9 groups of 12 mice each. The headline restorative result used 0.3 W/cm2, 5 min/day, for 10 days, applied against the shaved scalp with ultrasound coupling gel.
Flags from extraction
n_subjects— Paper states group size (12 mice) and an L9(3^3) orthogonal design (9 groups) but never gives a single combined total exposed to ultrasound; group sizes listed as a 9-element list rather than summed.exposures[0].target— PC12 is an immortalised rat pheochromocytoma cell line differentiated toward a neuron-like phenotype; no vocabulary target term matches a dish cell-line preparation, so 'other' was used.exposures[1].target— The transducer position on the head is not described relative to a specific brain region; the paper repeatedly calls the treatment 'low intensity non-focused ultrasound' aimed generally at the brain/striatum, so whole_brain_or_unfocused was used.exposures[0].unspecified_domain.ispta_w_cm2— The paper reports only 'intensity' without specifying ISPTA vs ISPPA or free-field vs in-situ; assigned to ispta_w_cm2/unspecified_domain because continuous-wave ISPPA=ISPTA and the FDA comparison discussed elsewhere in the paper is framed in terms of ISPTA limits.