Anti-inflammatory and Neuroprotective Effects of Transcranial Ultrasound Stimulation on Parkinson's Disease
Wen-Shin Song, Chen-Yu Sung, Chia-Hua Ke, Feng-Yi Yang
Ultrasound in Medicine & Biology 2022, 48, 265-274 · 10.1016/j.ultrasmedbio.2021.10.001
Abstract
Low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive neuromodulation tool for deep brain stimulation. Here, we investigated the impact of LIPUS, including neuroprotective effects, on the pathology of Parkinson's disease (PD) in an animal model. Sprague-Dawley rats were injected with 6-hydroxydopamine (6-OHDA) at two sites in the right striatum. LIPUS (1 MHz, 5% duty cycle, 1-Hz pulse repetition frequency, 15 min/d) stimulation was then applied to some of the rats (the 6-OHDA + LIPUS group) beginning 2 wk after the 6-OHDA administration, while the remaining rats (the 6-OHDA group) received no LIPUS stimulation. The 6-OHDA-induced inflammatory responses and expressions of neurotrophic factors were quantified with immunofluorescence activity. The safety of LIPUS was assessed using hematoxylin and eosin and Nissl staining. LIPUS treatment significantly inhibited 6-OHDA-induced glial activation and the phosphorylation of nuclear factor-κB p65 in the substantia nigra pars compacta. Further study revealed that LIPUS effectively preserved the levels of neurotrophic factors, dopamine transporter and tight junction proteins of the blood-brain barrier in the 6-OHDA + LIPUS group compared with the 6-OHDA group. These results indicate that LIPUS acts via multiple neuroprotective mechanisms in the PD rat model and suggest that LIPUS can be viewed as a potential treatment for PD.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to lesioned striatal region in 6-OHDA rat model of Parkinson's disease
Target: striatum — “the targeted region in the lesions of the brain (right striatum, 6-OHDA injection site)”
Device: Olympus / Panametrics · Panametrics · A392S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.528 | ✓✓✓⚑ |
| 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 |
The sonication was precisely targeted using a stereotaxic apparatus. The acoustic wave was delivered to the targeted region in the lesions of the brain. Each rat's right hemisphere was treated with LIPUS with triple sonications. The duration of each sonication was 5 min, and there was an interval of 5 min between sonications. LIPUS was applied consecutively to the rats in the 6-OHDA + LIPUS group 5 d/wk for 6 wk.
Flags from extraction
n_subjects— The 4 6-OHDA+LIPUS rats are the group with clear reported LIPUS exposure; the paper also mentions unspecified-number additional healthy rats used for H&E/Nissl safety evaluation ('healthy rats were selected for safety evaluation... over 5 d in 1 wk') without stating their group size, so they are not included in the total.n_sessions_per_subject— Computed as 3 sonications/day x 5 d/wk x 6 wk = 90 sonications, or 30 daily sessions; recorded as 30 (daily sessions) based on '5 d/wk for 6 wk' schedule.anaesthesia— Paper states rats were anesthetized with isoflurane for the 6-OHDA stereotaxic injections but does not explicitly state whether the animals were anesthetized during the LIPUS sonication sessions themselves.direction_of_effect— Study reports anti-inflammatory/neuroprotective histological outcomes, not a measured direction of neuromodulatory (excitatory/inhibitory) neural effect, so 'not_assessed' was used.exposures[0].free_field.ispta_w_cm2— Measured via radiation force balance in degassed water (no skull/tissue path stated for this measurement), assigned to free_field domain.