Neuroprotective effect of low-intensity transcranial ultrasound stimulation in endothelin-1-induced middle cerebral artery occlusion in rats
Shuo Wu, Tao Zheng, Juan Du, Yi Yuan, Qinglei Shi, Zhanqiu Wang, Defeng Liu, Jian Liu, Xiaohan Wang, Lanxiang Liu
Brain Research Bulletin 2020 · 10.1016/j.brainresbull.2020.05.006
Abstract
Background Ischemic stroke is one of the leading causes of death and disability worldwide. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective treatment for ischemic stroke. Diffusion-weighted imaging (DWI) can be highly sensitive in the detection of ischemic brain injury. Relative apparent diffusion coefficient (rADC) values can be used to evaluate the effect of LITUS on ischemic stroke. Purpose The aim of this study was to determine the neuroprotective effect of LITUS at different time points using endothelin-1-induced middle cerebral artery occlusion in rats as a model of ischemic stroke. Methods Endothelin-1 (ET-1) was injected into the cerebral parenchyma near the middle cerebral artery, which induced focal, reversible, low-flow ischemia in rats. After occlusion of the middle cerebral artery for 30 min, 120 min, and 240 min, LITUS stimulation was used respectively. DWI was performed at 1, 3, 6, 12, 18, 24, 48, and 72 h after ischemia using a 3 T scanner. The rADC values were calculated, and functional outcomes assessed using neurobehavioral scores after ischemia. Nissl staining and estimation of Na + -K + -ATPase activity were used to assess the neuropathology after completing the last Magnetic Resonance Imaging (MRI) examination. Results Endothelin-1-induced occlusion of the middle cerebral artery resulted in significant dysfunction and neuronal damage in rats. Rats that received LITUS exhibited reduced damage of the affected brain tissue after cerebral ischemia. The greatest protective effect was found when LITUS stimulation occurred 30 min after cerebral ischemia. Conclusions Imaging, behavioral, and histological results suggested that LITUS stimulation after an ischemic stroke produced significant neuroprotective effects.
Abstract via europepmc.
Exposures
Exposure 1: LITUS at 30, 120 or 240 min after ET-1
Target: cerebral cortex — “the injured cortical areas”
Device: Olympus / Panametrics · Olympus, Japan · V301-SU unfocused transducer ✓
| 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 | ✓✓✓⚑ |
Pulsed 500 kHz ultrasound, tone-burst duration 0.5 ms at PRF 1 kHz, stimulation duration 400 ms per train; total stimulation duration 10 min. Delivered through a 10 mm conical collimator at 30, 120 or 240 min after ET-1 injection.
Flags from extraction
exposures[0].timing.sonication_duration_s— 400 ms is the stated stimulation duration (train); total stimulation was 10 min, described in protocol_descriptionexposures[0].unspecified_domain.isppa_w_cm2— Isppa measured with a calibrated hydrophone but the paper does not say it was in water, so placed in unspecified domainexposures[0].timing.duty_cycle_pct— Duty cycle not statedsham_type— ET-1 group and saline control received no ultrasound; whether a transducer was placed is not statedn_subjects— Fifty rats in five groups of 10; only three groups received LITUS