Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model
Wei-Ting Lin, Ran-Chou Chen, Wen-Wei Lu, Shing-Hwa Liu, Feng-Yi Yang
Scientific Reports 2015, 5 · 10.1038/srep09671
Abstract
The protein expressions of neurotrophic factors can be enhanced by low-intensity pulsed ultrasound (LIPUS) stimulation in the brain. The purpose of this study was to demonstrate the protective effect of LIPUS stimulation against aluminum-induced cerebral damage in Alzheimer's disease rat model. LIPUS was administered 7 days before each aluminum chloride (AlCl3) administration, and concomitantly given with AlCl3 daily for a period of 6 weeks. Neurotrophic factors in hippocampus were measured by western blot analysis. Behavioral changes in the Morris water maze and elevated plus maze were examined in rats after administration of AlCl3. Various biochemical analyses were performed to evaluate the extent of brain damages. LIPUS is capable of prompting levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in rat brain. AlCl3 administration resulted in a significant increase in the aluminum concentration, acetylcholinesterase activity and beta-amyloid (Aβ) deposition in AlCl3 treated rats. LIPUS stimulation significantly attenuated aluminum concentration, acetylcholinesterase activity, Aβ deposition and karyopyknosis in AlCl3 treated rats. Furthermore, LIPUS significantly improved memory retention in AlCl3-induced memory impairment. These experimental results indicate that LIPUS has neuroprotective effects against AlCl3-induced cerebral damages and cognitive dysfunction.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS sonication of hippocampus
Target: hippocampus — “hippocampus (bilateral)”
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 |
LIPUS was generated by a 1-MHz focused piezoelectric transducer with 50 ms burst lengths at a 5% duty cycle and a repetition frequency of 1 Hz, aimed at a region 3.0 mm posterior and 2.5 mm lateral to bregma. Each rat hemisphere was treated by LIPUS with triple sonications; the duration of each sonication was 5 min with a 5 min interval between sonications. LIPUS was applied daily for 49 days, starting 7 days before AlCl3 administration and continuing through the 42 days of AlCl3 administration.
Flags from extraction
n_subjects— Total ultrasound-exposed animal count across the paper's separate sub-experiments is not stated; the group sizes reported are: Fig. 1 pilot western-blot experiment (n=4) and the main behavioural/biochemical study's two LIPUS-exposed arms (LIPUS n=6, LIPUS+AlCl3 n=6).direction_of_effect— This study reports biochemical/neuroprotective and behavioural (memory) outcomes rather than a direct measure of neuronal excitation or inhibition.