Transcranial ultrasound stimulation promotes brain-derived neurotrophic factor and reduces apoptosis in a mouse model of traumatic brain injury
Wei-Shen Su, Chun-Hu Wu, Szu-Fu Chen, Feng-Yi Yang
Brain Stimulation 2017, 10, 1032-1041 · 10.1016/j.brs.2017.09.003
Abstract
Background The protein expressions of brain-derived neurotrophic factor (BDNF) can be elevated by transcranial ultrasound stimulation in the rat brain. Objective The purpose of this study was to investigate the effects and underlying mechanisms of BDNF enhancement by low-intensity pulsed ultrasound (LIPUS) on traumatic brain injury (TBI). Methods Mice subjected to controlled cortical impact injury were treated with LIPUS in the injured region daily for a period of 4 days. Western blot analysis and immunohistochemistry were performed to assess the effects of LIPUS. Results The results showed that the LIPUS treatment significantly promoted the neurotrophic factors BDNF and vascular endothelial growth factor (VEGF) at day 4 after TBI. Meanwhile, LIPUS also enhanced the phosphorylation of Tropomyosin-related kinase B (TrkB), Akt, and cAMP-response element binding protein (CREB). Furthermore, treatment with LIPUS significantly decreased the level of cleaved caspase-3. The reduction of apoptotic process was inhibited by the anti-BDNF antibody. Conclusions In short, post-injury LIPUS treatment increased BDNF protein levels and inhibited the progression of apoptosis following TBI. The neuroprotective effects of LIPUS may be associated with enhancements of the protein levels of neurotrophic factors, at least partially via the TrkB/Akt-CREB signaling pathway.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to injured cortex after traumatic brain injury
Target: parietal lobe — “injured cortical areas over the right parietal cortex (craniotomy/CCI site)”
Device: Olympus / Panametrics · Panametrics · A392S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 50 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| 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 reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Ispta, domain unspecified (W/cm²) | 0.528 | ✓✓✓⚑ |
The transducer was applied with a duty cycle of 5% and a repetition frequency of 1 Hz. LIPUS was applied for a sonication time of 5 min at an acoustic power of 0.51 W, delivered 5 min after TBI and subsequently daily for a period of 3 days (4 days of treatment total), with mice sacrificed for analysis at 1 or 4 days.
Flags from extraction
n_subjects— Per-group animal counts (n=6-7) appear only in figure legends, not in the main text; total number of animals used is not stated in main text so recorded as not_reported.blinding— The paper states only that the two experimenters counting immunofluorescence-labelled cells were blinded to group; blinding of other outcome measures (western blot) or of treatment administration is not stated.exposures[0].unspecified_domain.ispta_w_cm2— The paper does not state whether the reported spatial-peak temporal-average intensity (528 mW/cm2) was measured in water/free field or estimated in situ; recorded as unspecified domain.exposures[0].timing.pulse_duration_ms— Duty cycle (5%) and PRF (1 Hz) are stated, which would imply a 50 ms pulse duration, but the paper never states a pulse duration directly; left as not_reported per protocol rather than computed.