Neuroprotective Effect of Low-Intensity Transcranial Ultrasound Stimulation in Moderate Traumatic Brain Injury Rats
Tao Zheng, Juan Du, Yi Yuan, Shuo Wu, Yinglan Jin, Zhanqiu Wang, Defeng Liu, Qinglei Shi, Xiaohan Wang, Lanxiang Liu
Frontiers in Neuroscience 2020 · 10.3389/fnins.2020.00172
Abstract
Traumatic brain injury (TBI) is a kind of severe brain injury characterized with a high incidence rate and a high disability rate. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective method for improving the functional prognosis of TBI. The fractional anisotropy (FA) value and mean diffusivity (MD) value can be sensitive to abnormal brain structure and function and can thus be used to evaluate the effect of LITUS on TBI. Our purpose was to evaluate the therapeutic effect of LITUS in a moderate TBI rat model with FA and MD values. For our method, we used 45 male Sprague Dawley rats (15 sham normal, 15 TBI, and 15 LITUS treatment rats). We used single-shot spin echo echo-planar imaging sequences at 3.0T to obtain the DTI parameters. Parameters of FA and MD on the treated side of the injury cortex were measured to evaluate the therapeutic effect of LITUS in a TBI rat model. For FA and MD values, groups were compared by using a two-way analysis of variance for repeated measures, and this was followed by Tukey's post hoc test. Differences were considered significant at P P = 0.0422) and significantly lower than that in the TBI group at 14, 21, and 35 days after TBI (adjusted P = 0.0015, 0.0064, and 0.0173, respectively). At the end of the scan time point, the differences between the two groups were not significant (adjusted P = 0.3242). The MD values in the LITUS treatment group were significantly higher in the early stage than that in the TBI group (adjusted P = 0.0167) and significantly lower at the following time points than in the TBI group. In conclusion, daily treatment with LITUS for 10 min effectively improved the brain damage in the Controlled Cortical Impact (CCI)-caused TBI model. FA and MD values can serve as evaluation indicators for the neuro-protective effect of LITUS.
Abstract via europepmc.
Exposures
Exposure 1: LITUS after CCI
Target: brain — “rat brain”
Device: Olympus / Panametrics · Olympus · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.4 | ✓✓✓⚑ |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 2.6 | ✓✓✓⚑ |
Unfocused transducer collimated to the rat brain; total stimulation of 10 min with 200 trials, once a day for 42 days after CCI. FF 500 kHz, PRF 1 kHz, SD 400 ms, TBD 0.5 ms.
Flags from extraction
n_subjects— 45 rats enrolled (15 sham, 15 TBI, 15 LITUS); only the 15 LITUS rats were sonicated.exposures[0].timing.sonication_duration_s— Text reads "400 and 0.5 ms" for SD and TBD; units read as ms for SD (400 ms) by order; 0.5 ms TBD.exposures[0].target.terms— Target is only "the rat brain"; stimulation position shown in Fig. 1B.sham_type— Sham Control rats had scalp incision and drilling without CCI or LITUS; the TBI group had CCI without LITUS. No ultrasound sham arm.blinding— Only the radiologists measuring FA/MD were stated as blinded to grouping.exposures[0].unspecified_domain.isppa_w_cm2— Isppa from hydrophone-calibrated pressure; medium not stated.anaesthesia— Anaesthesia during LITUS sessions not stated; pentobarbital used for surgery and MR scans.exposures[0].timing.duty_cycle_pct— Duty cycle not stated.