Low-Intensity Pulsed Ultrasound Attenuates Postoperative Neurocognitive Impairment and Salvages Hippocampal Synaptogenesis in Aged Mice
Qian Wang, Taotao Liu, Huixian Chang, Zhengqian Li, Lei Chen, Xinning Mi, Huayi Xing, Xiaoxiao Wang, Jingshu Hong, Kaixi Liu, Yitong Li, Dengyang Han, Yue Li, Ning Yang, Xiaoli Li, Yingwei Li, Xiangyang Guo
Brain Sciences 2023 · 10.3390/brainsci13040657
Abstract
Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanisms remains unknown. An experimental setup for LIPUS stimulation of the hippocampus was well established. A laparotomy model in aged mice was applied, and a Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of Piezo1, synapse-associated proteins in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. The results showed that LIPUS increased synapse-related proteins of the hippocampus and attenuated cognitive impairment in aged mice. Meanwhile, LIPUS suppressed the overexpression of Piezo1 in the hippocampus. We further found that LIPUS promoted Calpain1 activity and increased extracellular regulated protein kinases (Erk) phosphorylation. Our results suggested that LIPUS could improve cognitive impairment and increase hippocampal synaptogenesis through the Piezo1-mediated Calpain1/ Erk pathway. LIPUS could be used as an effective physical intervention to alleviate postoperative cognitive dysfunction in the aged population.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to dorsal hippocampus
Target: hippocampus — “dorsal hippocampus”
Device: not reported
| 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) | 150 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.177 | ✓✓✓ |
The duration of sonication was alternated bilaterally for 2.5 min and repeated three times, for a total stimulation time of 15 min, delivered at four time points around the anesthesia/surgery: 8 h before, 4 h before, 4 h after and 8 h after surgery. A calibrating cone was used so the focal point fell on the dorsal hippocampus (bregma +-1.40 mm, caudal -1.94 mm).
Flags from extraction
exposures[0].timing.pulse_duration_ms,exposures[0].timing.sonication_duration_s— Figure 1D explicitly labels the 50 ms value 'sonication duration (SD)'. Duty cycle (5%) divided by PRF (1 Hz, i.e. a 1 s period) arithmetically equals 50 ms, which would normally identify this as the per-pulse ON duration (pulse duration) rather than a train duration under the burst rule; the paper's own label was followed (sonication_duration_s=0.05) and pulse_duration_ms left not_reported rather than resolved by arithmetic.exposures[0].in_situ.method— The paper states the intensity value is 'after transcranial attenuation' but does not specify whether this was measured through an excised skull or computed using an assumed attenuation coefficient; classified as 'derating' with this ambiguity noted.device— No manufacturer or model is given for the ultrasound transducer itself; only the unrelated stereotaxic apparatus (RWD Life Science) is named.n_subjects— Different subsets of mice were used for different assays (Morris water maze n=12/group, RT-qPCR n=6/group, Western blot n=4/group, immunofluorescence n=3/group across four groups); no single total number of ultrasound-exposed animals is stated.