Transcranial focused ultrasound stimulation reduces vasogenic edema after middle cerebral artery occlusion in mice
Guo-Yuan Yang, Ji-Xian Wang, Li-Dong Deng, Lin Qi, Qian Suo, Sheng-Ju Wu, Muyassar Mamtilahun, Ru-Bing Shi, Ze Liu, Jun-Feng Sun, Yao-Hui Tang, Zhi-Jun Zhang
Neural Regeneration Research 2022, 17, 2058 · 10.4103/1673-5374.335158
Abstract
Blood-brain barrier (BBB) disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke. Reducing this disruption has therapeutic potential. Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke. Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling. However, its effect on the BBB in the acute phase of ischemic stroke is unknown. In this study of mice subjected to middle cerebral artery occlusion for 90 minutes, low-intensity low-frequency (0.5 MHz) transcranial focused ultrasound stimulation was applied 2, 4, and 8 hours after occlusion. Ultrasound stimulation reduced edema volume, improved neurobehavioral outcomes, improved BBB integrity (enhanced tight junction protein ZO-1 expression and reduced IgG leakage), and reduced secretion of the inflammatory factors tumor necrosis factor-α and activation of matrix metalloproteinase-9 in the ischemic brain. Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation, which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
Abstract via europepmc.
Exposures
Exposure 1: tFUS to left (ipsilateral) hemisphere after transient MCA occlusion
Target: hemisphere unspecified — “left hemisphere (ipsilateral to MCA occlusion), 2 mm beneath the cortical surface”
Device: custom-built · Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences ✓
| 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) | 0.3 | ✓✓✓ |
| 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) | 0.039 | ✓✓✓⚑ |
tFUS was applied to the left hemisphere for 10 minutes with the probe attached to the overlying skull, using a single-element focused ultrasound transducer. Parameters: fundamental frequency 500 kHz; spatial peak temporal average intensity 39 mW/cm2; pulse width 500 microseconds; pulse interval 1 ms; stimulation (train) duration 300 ms; stimulation interval 3 seconds. Treatment was given once, 2, 4, or 8 hours after occlusion depending on group.
Flags from extraction
n_subjects— 76 mice were enrolled in total across all 6 groups (12-13 per group), but only 4 of the 6 groups (sham/tFUS, tMCAO/tFUS at 2h/4h/8h) actually received active tFUS; the paper does not give an exact count of ultrasound-exposed animals, only the per-group range, so the total N=76 enrolled is recorded here.exposures[0].timing.pulse_repetition_frequency_hz— Paper reports pulse width (500 microseconds) and pulse interval (1 ms) rather than PRF directly; PRF was not computed here.exposures[0].timing.duty_cycle_pct— Duty cycle is not explicitly stated; it would require computing pulse width / (pulse width + pulse interval), which was not done here.exposures[0].unspecified_domain.ispta_w_cm2— The paper states a single 'spatial peak temporal average intensity' without specifying whether it was measured/derived in free field or in situ.direction_of_effect— Study measured edema, BBB integrity, inflammation and cerebral blood flow rather than neuronal excitability; classified as not_assessed.