Transcranial Ultrasound Stimulation Improves Long-Term Functional Outcomes and Protects Against Brain Damage in Traumatic Brain Injury
Szu-Fu Chen, Wei-Shen Su, Chun-Hu Wu, Tsuo-Hung Lan, Feng-Yi Yang
Molecular Neurobiology 2018, 55, 7079-7089 · 10.1007/s12035-018-0897-z
Abstract
The purpose of this study was to assess the long-term treatment efficacy of low-intensity pulsed ultrasound (LIPUS) on functional outcomes, brain edema, and the possible involvement of reactions in mice following traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury received LIPUS treatment daily for a period of 4 weeks. The effects of LIPUS on edema were detected by MR imaging in the mouse brain at 148 days following TBI. Long-term functional outcomes of LIPUS stimulation were evaluated by behavioral analyses. One-way or two-way analysis of variance and Student's t test were used for statistical analyses, with a significant level of .05. Up to post-injury day 148, treatment with LIPUS significantly improved functional outcomes (all p < 0.05). LIPUS also significantly attenuated brain edema and neuronal death at day 148 after TBI (all p < 0.05). Furthermore, LIPUS reduced MMP9 activity, neutrophil infiltration, and microglial activation at day 1 or day 4 following TBI (all p < 0.05). Meanwhile, LIPUS increased the Bcl-2/Bax ratio and enhanced the phosphorylation of Bad and FOXO-1 at day 1 or day 4 following TBI (all p < 0.05). Almost 5 months of follow-up showed that the treatment efficacy of post-injury LIPUS stimulation on reduced brain edema and improved functional outcomes persisted over time after TBI. The neuroprotective effects of LIPUS are associated with a reduction of early inflammatory events and inhibition of apoptotic progression.
Abstract via europepmc.
Exposures
Exposure 1: Daily LIPUS to injured parietal cortex after TBI
Target: parietal lobe — “injured cortical areas (right parietal cortex)”
Device: Olympus / Panametrics · Panametrics · A392S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| 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 | ✓✓✓⚑ |
LIPUS was applied for a sonication time of 5 min at an acoustic power of 0.51 W, 5 min after TBI and subsequently daily for a period of 27 days (i.e., once daily for 28 total treatment days).
Flags from extraction
n_subjects— Different group sizes (n=6 for zymography/immunohistochemistry endpoints, n=12 for behavioral endpoints) are used across different sub-experiments; no single total number of LIPUS-exposed animals is stated.n_sessions_per_subject— Paper states LIPUS given 5 min after TBI and then daily for 27 days; the exact total number of sessions (implying 28) is not stated as a single number.exposures[0].unspecified_domain.ispta_w_cm2— Domain (free-field vs in-situ) of the reported Ispta value is not stated by the paper.exposures[0].timing.waveform— Paper calls the device 'low-intensity pulsed ultrasound (LIPUS)' but does not state pulse duration, PRF, or duty cycle values in the main text.