Wearable Ultrasound Improves Motor Function in an MPTP Mouse Model of Parkinson's Disease
Hui Zhou, Lili Niu, Xiangxiang Xia, Zhengrong Lin, Xiufang Liu, Min Su, Ruibiao Guo, Long Meng, Hairong Zheng
IEEE Transactions on Biomedical Engineering 2019, 66, 3006-3013 · 10.1109/tbme.2019.2899631
Abstract
Objective Low-frequency low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive neuromodulation tool. The aim of this study is to examine whether LIPUS stimulation of the motor cortex can improve parkinsonian motor deficit in a mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods Acute Parkinson's disease (PD) mouse model is built by injection of MPTP (20 mg/kg) every 4 h in a total of four doses in one day. Mice are randomized into control, MPTP, sham-LIPUS+MPTP, and LIPUS+MPTP group. For LIPUS+MPTP group, 7 days of LIPUS (800 kHz, 10% duty cycle, 100-Hz pulse repetition frequency, 40 min/day) is delivered to the motor cortex. An open field test (OFT) is conducted on day 4 and a pole test on day 5, respectively. Striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) are measured on day 8. The safety of LIPUS is verified using Hematoxylin and esosin (HE) staining and Nissl staining. Results LIPUS treatment improves rearing number in the OFT on day 4 (n = 8, p = 0.037) and locomotor activity in the pole test on day 5 (n = 8, p = 0.007) compared with the sham-LIPUS+MPTP group. Moreover, LIPUS increases T-SOD (n = 7, p = 0.006) and GSH-PX (n = 7, p = 0.030) compared with the sham-LIPUS+MPTP group. In addition, HE and Nissl staining shows no brain tissue injury induced by LIPUS. Conclusion These findings demonstrate that LIPUS may have neuromodulation effects in PD mice. Significance LIPUS may provide a novel neuromodulation tool for PD treatment.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS stimulation of motor cortex via wearable transducer
Target: primary motor cortex — “motor cortex (M1)”
Device: custom-built · custom-built wearable single-element focused transducer (PZT-5H/epoxy 1-3 composite)
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 800 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 6 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 151 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 0.76 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.076 | ✓✓✓ |
LIPUS was delivered to awake, freely-moving mice via a wearable transducer fixed to the skull with a collimator, for 40 min/day from day 1 to day 7 after MPTP injection, with an inter-stimulus-interval of 10 s between 6-s trains.
Flags from extraction
n_subjects— n_subjects reflects the primary behavioural LIPUS+MPTP group (n=8); additional ultrasound-exposed cohorts used for c-Fos immunohistochemistry (n=3) and histological safety testing (up to 12 mice) are not included in this total.anaesthesia— Mice were anaesthetised for the initial stereotaxic transducer-mounting surgery but stimulated awake and freely moving thereafter; recorded as 'both'.exposures[0].free_field.*— Only the post-skull (in_situ) intensity/pressure values are explicitly stated as numbers; the free-field (no-skull) values are described only as an ~11% relative decrease, not given as absolute numbers.