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A novel therapeutic approach of ultrasound stimulation to restore forelimb functions following cervical cord injury in rats

Rakib Uddin Ahmed, Monzurul Alam, Shuai Li, Poornima Palanisamy, Hui Zhong, Yong-Ping Zheng

Journal of Neurorestoratology 2023, 11, 100067 · 10.1016/j.jnrt.2023.100067

rodentotherbehaviouremg mep
SpeciesSprague-Dawley rat (female)
Subjects10, 6, 4swept animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutsbehaviour, emg mepforelimb reaching and grasping success rate; grip strength; EMG of extensor and flexor digitorum muscles
Direction of effectmixed or unclearLIPUS improved forelimb reaching/grasping success versus control at weeks 2-3 post-injury, but the benefit did not persist beyond week 3 when LIPUS was given alone; combined LIPUS+Buspirone produced more consistent improvement through week 6. Grip strength did not differ significantly between LIPUS and control groups except a within-group improvement in the LIPUS group at week 6.
Adverse eventsnot reportedHistopathological examination of the spinal cord after LIPUS stimulation was not performed, and the thermal effects of the stimulation were not considered negligible, which the authors note as limitations.

Exposures

Exposure 1: LIPUS stimulation of the cervical spinal cord (C4)

Target: cervical spinal cord — “cervical cord (C4 level, above the dorsal-funiculus crush)
Device: custom-built · Beijing Quanxin Ultrasonic Co. Ltd · PZT-8

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)20✓✓
Sonication duration (s)600✓✓
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)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

An implantable piezoelectric probe delivered pulsed LIPUS (1 MHz, 20% duty cycle, 1 kHz PRF) directly above the C4 dorsal funiculus crush. Stimulation was provided for about 10 min during the reaching and grasping task; a separate sentence in Methods states stimulation for 5 min before the behavior task followed by 10 min during the task, so the exact nested timing is not fully clear.

Flags from extraction

  • n_subjectsOverlapping and inconsistent group sizes are reported across sub-experiments (e.g. LIPUS n=10 in experiment 1; LIPUS n=6, combined n=4 or n=7 in experiment 2), with no single stated total of ultrasound-exposed animals.
  • n_sessions_per_subjectLIPUS was delivered 'during the reaching and grasping task' across weekly behavioral tests over up to 6 weeks post-injury, but the exact number of stimulation sessions per animal is not stated.
  • exposures[0].timing.sonication_duration_sMethods text gives two different session-duration statements ('after 5 min of therapeutic stimulation, the behavior task was conducted' vs. 'LIPUS stimulation was delivered for 10 min during the reaching and grasping task'); the Results section's explicit 'about 10 min' was used, but the discrepancy is unresolved.
  • exposures[0].free_field.ispta_w_cm2Reported metric is ISATA (spatial-average temporal-average intensity), not ISPTA; recorded here as the closest matching schema field.
  • exposures[0].in_situ.ispta_w_cm2Ex vivo intensity inside the vertebral canal is reported generically as 'intensity' (same ISATA-style measurement as the free-field value), not explicitly labelled ISPTA.