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An Evaluation Model for Brain Ischemia Protection in Mice by Low-Intensity Pulsed Ultrasound Stimulation Based on Functional Cortico-Muscular Coupling

Ziqiang Jin, Xiaoling Chen, Zechuan Du, Yi Yuan, Xiaoli Li, Ping Xie

Bioengineering 2025 · 10.3390/bioengineering12050541

rodentstrokeinvasive electrophysiologyemg mep

Abstract

(1) Background: Ischemic stroke is a major global public-health concern with complex pathogenesis. Current treatment strategies face challenges. Low-intensity pulsed ultrasound stimulation (LIPUS), a non-invasive neuromodulation technology, shows promise in treating ischemic stroke, yet its underlying mechanisms lack in-depth investigation, especially in quantitative efficacy evaluation. (2) Methods: This study aimed to develop a neuromuscular functional coupling-based dynamic time warping (DTW) model to evaluate LIPUS's neuroprotective effects in a mouse model of ischemic stroke. A bilateral carotid artery occlusion (BCAO) model in mice was established, and LIPUS treatment was given. Time- and frequency-domain analyses of local field potentials (LFPs) and electromyography (EMG) were conducted, and outcomes were quantified using a percentage-based scoring system. (3) Results: The BCAO+LIPUS group scored significantly higher than the BCAO group. (4) Conclusions: This study demonstrated that LIPUS is neuroprotective in BCAO mice and that the DTW-100 assessment evaluation model can quantify the neuroprotective effects of LIPUS.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects39 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutsinvasive electrophysiology, emg mepLocal field potential (LFP) recorded from primary motor cortex (M1) and electromyography (EMG) recorded from tail muscles
Direction of effectbidirectionalAfter LIPUS, LFP DTW-100 scores in BCAO mice rose markedly (e.g. 55-71 pre to 77-82 post) while EMG DTW-100 scores fell (e.g. 38-56 pre to 52-63 post), indicating increased cortical (LFP) coupling to the reference and decreased EMG coupling.
Adverse eventsnot reported

Exposures

Exposure 1: LIPUS to primary motor cortex (M1) in BCAO mice

Target: primary motor cortex — “primary motor cortex (M1)
Device: Olympus / Panametrics · Olympus · V301-SU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot 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)0.95?
Protocol, in the paper’s words

The ultrasound parameters were configured as follows: fundamental frequency = 500 kHz, pulse repetition frequency = 1 kHz, duty cycle = 50%, stimulation duration = 300 ms, and inter-trial interval = 4 s. Each sample underwent 30 cycles of testing.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2Text states Isppa was 'measured using a hydrophone' 'at the tail motor cortex', which is ambiguous/possibly an OCR or wording error for the target location; unclear whether this was a free-field water-tank measurement or an in-situ/through-skull measurement, so placed in unspecified_domain.
  • n_subjectsPaper states 39 total mice used in experimental procedures (9 underwent BCAO surgery); a separate sentence refers to 'the normal group of 30 samples', which may denote 30 distinct normal mice or repeated trials from a smaller number of mice. Total of 39 taken from the explicit headline count.
  • exposures[0].timing.pulse_duration_msDuty cycle (50%) and PRF (1 kHz) are both stated, which would allow pulse duration to be computed (0.5 ms), but the paper does not state pulse duration directly, so it is left not_reported per the no-arithmetic rule.
  • direction_of_effectStudy reports a functional-coupling/neuroprotection score (DTW-100), not a direct excitatory/inhibitory neurophysiological readout; classified as bidirectional based on opposite-direction changes in LFP vs EMG DTW-100 scores after LIPUS.