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Low-Intensity Transcranial Ultrasound Stimulation Promotes Recovery in Blood Flow and Movement Following Prolonged Anesthesia

Hang Song, Yinuo Zeng, Liyuan Ren, Huan Zhang, Aitao Wang, Junfeng Sun, Shanbao Tong

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2025 · 10.1109/tnsre.2025.3575456

rodenthealthycerebral haemodynamicsbehaviourhistology molecular

Abstract

General anesthesia is a routine operation before surgical and diagnostic procedures. However, delayed emergence from anesthesia can lead to various complications. Researchers have sought to use transcranial ultrasound stimulation to promote motor and cognitive function recovery after short-period anesthesia ( 90 min) would affect ultrasound-induced recovery remains unclear. In this study, we investigated the effects of ultrasound stimulation on the recovery of mice after prolonged anesthesia by analyzing the changes of cortical blood flow and movement. C57BL/6 mice (n =24) were randomly assigned to the three groups: Control, Sham, and Ultrasound Stimulation. We utilized laser speckle contrast imaging to record cortical blood flow during and after 120 min anesthesia. Additionally, we recorded the emergence time of the first and full movements as indicators of recovery. The results showed that ultrasound stimulation significantly accelerated the recovery of blood flow (F(2,21) =3.83, p =0.038, $\eta _{p}^{{2}} =0.267$ ) and reduced the emergence time of the first movement (F(2,21) =2.70, p =0.091, $\eta _{p}^{{2}} =0.205$ ) after 120 min anesthesia. Furthermore, we observed a medium negative correlation between the blood flow after 120 min anesthesia and the emergence time of the first movement (r(22) $= -0.487$ , p =0.016, 95% CI: [-0.744,-0.104]). These findings revealed the potential of ultrasound stimulation to facilitate recovery after prolonged anesthesia.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjectsnot reported animals
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer, no treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaboth
Readoutscerebral haemodynamics, behaviour, histology molecular — laser speckle contrast imaging of cortical blood flow; time to first movement and full movement (righting reflex); H&E staining
Direction of effectexcitatory5 min TUS to CA1 immediately after 120 min isoflurane anaesthesia accelerated recovery of cortical blood flow and shortened time to first movement; TUS during prolonged anaesthesia did not accelerate recovery.
Adverse eventsnone observedH&E staining showed no signs of microhemorrhage, edema, or cell necrosis in exposed areas; theoretical temperature rise estimated below 0.01 C.

Exposures

Exposure 1: TUS of CA1

Target: CA1 — “CA1 region”
Device: Olympus / Panametrics · Olympus NDT · V318-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.4 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,500✓✓✓
Duty cycle (%)60✓✓✓⚑
Sonication duration (s)1✓✓✓
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 estimatemeasurementsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)5.72✓✓✓⚑
In-situ Ispta (W/cm²)not reported
Isppa, domain unspecified (W/cm²)5.95✓✓✓⚑
Protocol, in the paper’s words

1 s sonications with 4 s inter-stimulus interval, delivered for 5 min to CA1; given after (main experiment) or during isoflurane anaesthesia, or after 60 min anaesthesia in a short-anaesthesia comparison.

Flags from extraction

  • exposures[0].timing.duty_cycle_pct — Duty cycle appears as 'DC = 60%' with OCR corruption ('\Delta C = 6 0 \%'); likely OCR error.
  • n_subjects — 58 mice across four experiments including Control and Sham groups and a preliminary experiment; sonicated subset is smaller.
  • exposures[0].unspecified_domain.isppa_w_cm2 — 5.95 W/cm2 stated in the parameters paragraph without domain; measurement in water and through skull described afterwards.
  • exposures[0].in_situ.isppa_w_cm2 — Transcranial measurement through a mouse skull with collimator, 5.72 W/cm2 (supplementary Fig. S1a).
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated; protocol has 1 s SD, PRF 1.5 kHz, DC 60%.
  • anaesthesia — Main experiment: TUS after isoflurane ceased; second experiment: TUS during isoflurane anaesthesia.