Restoration of Glymphatic Influx After Photothrombotic Stroke Using Low-Intensity Focused Ultrasound

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/cm², 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.

Keywords: cerebrospinal fluid; glymphatic; low‐intensity focused ultrasound; stroke.