Restoration of Glymphatic Influx After Photothrombotic Stroke Using Low‐Intensity Focused Ultrasound
Ming‐Yen Hsiao, Yu‐Ling Lin, Meng‐Ting Lin, Wei‐Hao Liao, Wen‐Shiang Chen, Chueh‐Hung Wu
CNS Neuroscience & Therapeutics 2025 · 10.1111/cns.70451
Abstract
Aims This study aimed to investigate the regional modulation effect of low-intensity focused ultrasound (LIFU) on cerebrospinal fluid (CSF) influx dynamics, focusing on the differential changes between hemispheres in a mouse model of unilateral ischemic stroke. Methods LIFU was administered with a commercial transducer at the unilateral M1 cortex of mice using specific parameters (0.5 MHz center frequency, 250 kHz pulse repetition frequency, 300 ms burst duration, 2 ms pulse length, 50% intraburst duty factor, 2 s interstimulation interval, spatial peak temporal average intensities of 0.5 W/cm 2 , and a total sonication duration of 10 min). The regional CSF influx was observed through in vivo macroscopy and brain section imaging in a photothrombotic stroke model, both with and without LIFU. Results Localized LIFU stimulation at the M1 region triggered a rapid CSF influx, peaking 20-30 min poststimulation. Following photothrombotic stroke, a marked reduction in CSF influx was observed in both ipsilesional and contralesional MCA regions, most notably on Days 1 and 3, with a return to baseline by Day 7. However, daily contralesional LIFU stimulation for 7 days effectively restored CSF influx on both sides. Conclusion Daily contralesional LIFU stimulation restores impaired CSF influx bilaterally after stroke, suggesting potential therapeutic implications for stroke-related pathophysiology.
Abstract via europepmc.
Exposures
Exposure 1: LIFU at M1 (ipsilesional, contralesional or central cerebrum)
Target: primary motor cortex — “M1 cortex of the brain”
Device: Sonic Concepts · Sonic Concepts · H-104 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250,000 | ✓✓✓⚑ |
| Duty cycle (%) | 50pulse duration × PRF gives 50000%, which disagrees with the stated value | ✓✓✓⚑ |
| 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) | 0.5 | ✓✓✓⚑ |
Pulse train of 300 ms (2 ms pulses, 50% pulse-train duty cycle) every 2 s for a total of 10 min; the paper states an overall duty cycle of 7.5%. In the stroke experiments LIFU was applied daily for up to seven days to ipsilesional M1, contralesional M1 or central cerebrum.
Consistency checks: pd exceeds period.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Paper states PRF = 250 kHz; with a 2 ms pulse at 50% this looks like a typo for 250 Hz. Recorded as written (250000 Hz).exposures[0].timing.duty_cycle_pct— 50% is the duty cycle within the pulse train; the paper gives an overall duty cycle of 7.5% in the Discussion.exposures[0].timing.sonication_duration_s— Pulse train duration 300 ms recorded; total repetition duration 10 min.n_subjects— Only per-experiment group sizes are given across many figures; no total.blinding— Experimenter could not be blinded to group.exposures[0].unspecified_domain.ispta_w_cm2— Intensity domain not stated.