Low-Intensity Pulsed Ultrasound Enhances Neurotrophic Factors and Alleviates Neuroinflammation in a Rat Model of Parkinson’s Disease
Chen-Yu Sung, Pai-Kai Chiang, Che-Wen Tsai, Feng-Yi Yang
Cerebral Cortex 2021 · 10.1093/cercor/bhab201
Abstract
Low-intensity pulsed ultrasound (LIPUS) has also been reported to improve behavioral functions in Parkinson's disease (PD) animal models; however, the effect of LIPUS stimulation on the neurotrophic factors and neuroinflammation has not yet been addressed. PD rat model was built by injection of 6-hydroxydopamine (6-OHDA) in 2 sites in the right striatum. The levels of neurotrophic factors and lipocalin-2 (LCN2)-induced neuroinflammation were quantified using a western blot. Rotational test and cylinder test were conducted biweekly for 8 weeks. When the 6-OHDA + LIPUS and 6-OHDA groups were compared, the locomotor function of the 6-OHDA + LIPUS rats was significantly improved. After LIPUS stimulation, the tyrosine hydroxylase staining density was significantly increased in the striatum and substantia nigra pars compacta (SNpc) of lesioned rats. Unilateral LIPUS stimulation did not increase brain-derived neurotrophic factor in the striatum and SNpc of lesioned rats. In contrast, unilateral LIPUS stimulation increased glial cell line-derived neurotrophic factor (GDNF) protein 1.98-fold unilaterally in the SNpc. Additionally, LCN2-induced neuroinflammation can be attenuated following LIPUS stimulation. Our data indicated that LIPUS stimulation may be a potential therapeutic tool against PD via enhancement of GDNF level and inhibition of inflammatory responses in the SNpc of the brain.
Abstract via europepmc.
Exposures
Exposure 1: 6-OHDA LIPUS group
Target: striatum, substantia nigra — “the targeted region in the lesions of the brain”
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 |
Each right hemisphere received triple sonications of 5 min with a 5 min interval between sonications, 5 days per week for 6 weeks (weeks 3 to 8), under isoflurane.
Flags from extraction
n_subjects— Only per-group n is given (n = 8 for behaviour, n = 4 for histology and western blot); 50 rats received 6-OHDA and 18 were excluded. Recorded the LIPUS group size from the behaviour figure legend.exposures[0].free_field.ispta_w_cm2— Paper writes 'spatial-peak, temporal-average intensity (I )' with the subscript lost in extraction; read as Ispta. Measured by radiation force balance in degassed water.exposures[0].timing.sonication_duration_s— Each sonication is 5 min, three per session with 5 min gaps; 5 days per week for 6 weeks. Number of sessions not stated.randomised— Rats were 'divided into' groups; randomisation is not stated.blinding— Behavioural testing and TH quantification were by a blinded investigator; treatment blinding not described.