Protective effect of low-intensity transcranial ultrasound stimulation after differing delay following an acute ischemic stroke
Lanxiang Liu, Juan Du, Tao Zheng, Shuo Hu, Yanchao Dong, Dan Du, Shuo Wu, Xuemei Wang, Qinglei Shi
Brain Research Bulletin 2019, 146, 22-27 · 10.1016/j.brainresbull.2018.12.004
Abstract
Background Ischemic stroke is a clinically common disease requiring early treatment in the acute period of stroke onset. Such early treatment reduces the level of brain injury, promotes functional recovery, and improves long-term prognosis. Previous studies have demonstrated that, in the event of an acute ischemic stroke, low-intensity transcranial ultrasound stimulation (LITUS) can provide neuroprotection. However, from existing studies, the protective effect of LITUS with differing delay after an acute ischemic stroke remains unclear. Objective The aim of the present study is to investigate whether the protective effect of LITUS in the event of an acute ischemic stroke differs with the time delay between the stroke and the application of LITUS. Methods In the present study, 60 Sprague Dawley rats (250 ± 10 g) were divided randomly into five groups (each group including LITUS group (6 rats) and control group (CTRL group: 6 rats)) with different treatment delays (0.5 h, 1 h, 3 h, 6 h, and 9 h). The rats were made to have an ischemic stroke by means of a distal middle cerebral artery occlusion. Next, magnetic response (MR) imaging was performed 15 min before LITUS in each group (marked as Pre-Stim). Once the MR imaging was finished, the rats were stimulated with ultrasound for 10 min (I sppa = 2.6 W/cm 2 , fundamental frequency: 500 kHz, duty cycle: 50%, stimulation duration: 400 ms) in the LITUS groups and went without ultrasound stimulation in the control (CTRL) group. Then, MR imaging was performed once every hour for three hours after LITUS (marked as Post-Stim (1 h), Post-Stim (2 h), and Post-Stim (3 h)). Finally, triphenyltetrazolium chloride staining of the rat brain tissues was performed. We analyzed the apparent diffusion coefficient (ADC) of the lesion area in Pre-Stim and Post-Stim and evaluated the differences between the LITUS groups and the CTRL group for the different treatment delays (0.5 h, 1 h, 3 h, 6 h, and 9 h). Results Compared to the CTRL group, LITUS significantly inhibited the ADC decrease (i) at the Post-Stim (1 h), Post-Stim (2 h), and Post-Stim (3 h) stages when the rats were stimulated at 0.5 h, (ii) at Post-Stim (1 h) and Post-Stim (2 h) when the rats were stimulated at 1 h and 3 h, and (iii) at Post-Stim (1 h) when the rats were stimulated at 6 h. There was no significant change in the ADC at Post-Stim (1 h), Post-Stim (2 h), and Post-Stim (3 h) when the rats were stimulated at 9 h. Conclusion In the event of an acute ischemic stroke, LITUS can inhibit the decrease of ADC and the effect is closely related to the delay in treatment. The earlier the ultrasound intervention, the better the protective effect.
Abstract via europepmc.
Exposures
Exposure 1: LITUS applied to ischemic cortex after distal MCA occlusion, at delays of 0.5, 1, 3, 6 or 9 h
Target: cerebral cortex — “ischemic cortex following distal middle cerebral artery occlusion (dMCAO)”
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 (%) | 50pulse duration × PRF gives 50% | ✓✓✓⚑ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 2.6 | ✓?⚑ |
| 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 |
The total stimulation duration was 10 min with 200 trials. The ultrasound FF and PRF were 500 kHz and 1 kHz, respectively. The ultrasound SD and TBD were 400 ms and 0.5 ms, and the Isppa value was 2.6 W/cm2. LITUS was performed once, at 0.5 h, 1 h, 3 h, 6 h, or 9 h after dMCAO depending on group; MR imaging was performed 15 min before (Pre-Stim) and 1, 2, and 3 h after (Post-Stim) LITUS.
Flags from extraction
sham_type— CTRL group 'went without ultrasound stimulation' and 'received the same experimental protocol' but the paper does not describe whether a transducer was placed without power (inactive_transducer) or simply omitted; mechanism of the control is not described.n_subjects— Total of 60 rats were enrolled (30 LITUS + 30 CTRL); n_subjects here counts only the 30 rats that received active ultrasound (LITUS groups).exposures[0].timing.duty_cycle_pct— Duty cycle is not stated as a percentage in the text; PRF (1 kHz) and pulse duration (0.5 ms) are given separately and left unconverted per protocol.exposures[0].free_field.isppa_w_cm2— Domain assumed free_field because pressure/intensity was measured by hydrophone without stated skull/tissue path; paper does not explicitly label this as a free-field or in-situ value.