Low-Intensity Pulsed Ultrasound Protects SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity by Upregulating Neurotrophic Factors
Yu-Cheng Liu, Wei-Shen Su, Tai-Ho Hung, Feng-Yi Yang
Ultrasound in Medicine & Biology 2024 · 10.1016/j.ultrasmedbio.2024.01.004
Abstract
Objective Neonatal hypoxic-ischemic brain damage (HIBD) can have long-term implications on patients' physical and mental health, yet the available treatment options are limited. Recent research has shown that low-intensity pulsed ultrasound (LIPUS) holds promise for treating neurodegenerative diseases and traumatic brain injuries. Our objective was to explore the therapeutic potential of LIPUS for HIBD. Methods Due to the lack of a suitable animal model for neonatal HIBD, we will initially simulate the therapeutic effects of LIPUS on neuronal cells under oxidative stress and neuroinflammation using cell experiments. Previous studies have investigated the biologic responses following intracranial injection of 6-hydroxydopamine (6-OHDA). In this experiment, we will focus on the biologic effects produced by LIPUS treatment on neuronal cells (specifically, SH-SY5Y cells) without the presence of other neuroglial cell assistance after stimulation with 6-OHDA. Results We found that (i) pulsed ultrasound exposure, specifically three-intermittent sonication at intensities ranging from 0.1 to 0.5 W/cm², did not lead to a significant decrease in viability among SH-SY5Y cells; (ii) LIPUS treatment exhibited a positive effect on cell viability, accompanied by an increase in glial cell-derived neurotrophic factor (GDNF) levels and a decrease in caspase three levels; (iii) the administration of 6-OHDA had a significant impact on cell viability, resulting in a decrease in both brain cell-derived neurotrophic factor (BDNF) and GDNF levels, while concurrently elevating caspase three and matrix metalloproteinase-9 (MMP-9) levels; and (iv) LIPUS treatment demonstrated its potential to alleviate the changes induced by 6-OHDA, particularly in the levels of BDNF, GDNF, and tyrosine hydroxylase (TH). Conclusion LIPUS treatment may possess partial therapeutic capabilities for SH-SY5Y cells damaged by 6-OHDA neurotoxicity. Our findings enhance our understanding of the effects of LIPUS treatment on cell viability and its modulation of key factors involved in the pathophysiology of HIBD and show the promising potential of LIPUS as an alternative therapeutic approach for neonates with HIBD.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS on SH-SY5Y cells with or without 6-OHDA
Target: cultured neurons — “SH-SY5Y cells”
Device: Mettler · Mettler Electronics, Inc. (Anaheim, CA) · ME740 generator with ME7410 1-MHz plane transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| 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 applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
LIPUS with a burst length of 5 ms at 50% duty cycle and 100 Hz repetition; either a single 5 min sonication or three 5 min episodes spaced 5 min apart; cells collected 24 h later.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Paper says 'burst length of 5 ms'; with 50% duty cycle and 100 Hz PRF the burst is the short pulse (resolved by arithmetic).exposures[0].unspecified_domain.ispta_w_cm2— Paper reports only 'spatial average intensity' (0.1, 0.3, 0.5 W/cm2) measured by radiation force balance in degassed water; not labelled ISPPA or ISPTA, so recorded as unspecified. 0.3 W/cm2 used for the 6-OHDA experiments.exposures[0].timing.sonication_duration_s— Three 5 min sonications spaced 5 min apart (a single 5 min episode was also tested); recorded 300 s per episode.n_subjects— Group sizes vary by figure (n = 4 to 8 per group); no total given.conditions— 6-OHDA exposure of SH-SY5Y cells used as a cell model for neonatal hypoxic-ischemic brain damage.sham_type— Sham controls are mentioned but how they were produced is not described.