Low-intensity (400 mW/cm 2 , 500 kHz) pulsed transcranial ultrasound preconditioning may mitigate focal cerebral ischemia in rats
Hangdao Li, Junfeng Sun, Daqu Zhang, Daryl Omire-Mayor, Peter A. Lewin, Shanbao Tong
Brain Stimulation 2017, 10, 695-702 · 10.1016/j.brs.2017.02.008
Abstract
Background Preconditioning methods, which could increase tolerance of brain to subsequent ischemic injuries with a small dose of non-injury stimuli, have gained attention. Capitalizing on noninvasiveness and safety of ultrasound modality, the pulsed transcranial ultrasound stimulation (pTUS) approach may provide a novel treatment for patients with high risk of stroke. Objective This study's goal was to investigate whether the risk of stroke could be minimized or eliminated by prior exposure to low-intensity, pulsed transcranial ultrasound stimulation (pTUS). Methods Rats were randomly assigned to control (n = 12) and pTUS preconditioning (pTUS-PC) groups (n = 14). The animals in pTUS-PC group were exposed to transcranial ultrasound stimulation before the induction of photothrombotic stroke, whereas control animals were handled identically but without the ultrasound stimulation. Cerebral blood flow was monitored using laser speckle imaging in both groups during stroke induction, as well as 24 and 48 h after stroke, respectively. Also, infarct volumes and edema were measured at 48 h after stroke. Results pTUS-PC rats had smaller ischemic areas during stroke induction, and 24 and 48 h after the stroke, and smaller infarct volume (1.770 ± 0.169%) than the controls (3.215 ± 0.401%) (p Conclusion These results support the hypothesis that transcranial ultrasound stimulation applied before photothrombosis could provide neuroprotection by increasing the brain's tolerance to subsequently induced focal ischemic injury.
Abstract via europepmc.
Exposures
Exposure 1: pTUS preconditioning of primary somatosensory cortex before photothrombotic stroke
Target: primary somatosensory cortex — “the primary somatosensory cortex of the rat brain (right primary hind-limb somatosensory cortex)”
Device: Olympus / Panametrics · Olympus NDT · V301-SU
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 5% | |
| Sonication duration (s) | 10 | ✓✓✓ |
| 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 | |
| Pressure, domain unspecified (kPa) | 589 | ✓? |
| Ispta, domain unspecified (W/cm²) | 0.402 | ✓? |
The ultrasound exposure was software-controlled: a 10 s single sequence (i.e., 1000 tone bursts) was repeated 180 times at a 10 s interval and delivered to the rat cortex before the induction of photothrombotic stroke. The pTUS-PC group was exposed to ultrasound treatment for 60 min total (chosen for comparison with a prior study). The control group was handled identically, including anaesthesia, but without the ultrasound stimulation.
Flags from extraction
n_subjects— 14 rats were enrolled in the pTUS-PC (ultrasound-exposed) group; 2 of these died before the 48 h endpoint and were excluded from analysis (enrolled n=14, analysed n=12). n_subjects reflects enrolled/exposed animals.exposures[0].unspecified_domain— The paper states the peak pressure (589 kPa) and corresponding Ispta (402 mW/cm2) as 'delivered to the rat cortex' but does not explicitly state whether this was measured in water/free field, through the thinned skull, or simulated; classified as unspecified domain.sham_type— The paper states the control group was 'handled identically to the pTUS-PC group, with the exception of the ultrasound stimulation' but does not explicitly describe whether a transducer was placed without power (inactive_transducer) or simply omitted.