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Ultrasonic neuromodulation as a new therapy for spasticity in an animal model of spastic cerebral palsy

Gisely de Andrade Costa Pereira, André Luiz Oliveira Poleto, Aldo José Fontes-Pereira, Marco Antônio von Krüger, Wagner Coelho de Albuquerque Pereira

Acta Cirúrgica Brasileira 2024 · 10.1590/acb394924

rodentotherbehaviour

Abstract

Purpose This study aimed to evaluate a new therapeutic option for the spasticity using ultrasound neuromodulation in an animal model of spastic cerebral palsy. Methods Thirty-two adult male Wistar rats were randomly distributed in: negative control (NC); positive control (PC); untreated model (UTM); and treated model (TM). Rats in the control groups received sham surgery, and rats in the model groups received the spastic cerebral palsy model surgery. The rats' motor functions were evaluated by the Rotarod and CatWalk tests before and after surgery. PC and TM groups underwent ultrasonic neuromodulation by a physiotherapeutic ultrasound (intensity 0.1 W/cm2, at 1 MHz) continuous mode for 5 seconds, for seven days. Results Twelve rats showed a spastic pattern (UTM = 6 and TM = 6), motor limitations (UTM = 6 and TM = 6), and ten had difficulty feeding (UTM = 5 and TM = 5). One UTM group rat could not recover its preoperative latency time, while the other rats in the model groups did. The speed at which the limbs swung reduced after surgery and increased in subsequent assessments, demonstrating greater instability and a deficit in locomotion balance. Conclusions Results were not yet sufficient to assert ultrasound neuromodulation as a possible therapy for spasticity in spastic cerebral palsy in the parameters used, and more studies are necessary.

Abstract via europepmc.

Speciesrat (Wistar, Rattus norvegicus)
Subjects8, 8swept animals
Sessions per subject7
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutsbehaviour — Rotarod latency; CatWalk gait analysis
Direction of effectmixed or unclearThe authors state results were not yet sufficient to assert ultrasound neuromodulation as a therapy for spasticity at these parameters.
Adverse eventsnot reportedSeveral rats died after the model surgery; no ultrasound-related adverse events are described.

Exposures

Exposure 1: Transcranial ultrasound over the ethanol injection site (pyramidal tract region)

Target: corticospinal tract — “the area where the ethanol was injected”
Device: other named manufacturer · KLD Biosistemas Equipamentos Eletronicos, Amparo, SP, Brazil · AVATAR III TUS0203 ✓

Pulse timing
Waveformcontinuous
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)not applicable
Pulse repetition frequency (Hz)not applicable
Duty cycle (%)not applicable
Sonication duration (s)5✓✓✓
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)0.1✓✓✓⚑
Protocol, in the paper’s words

Continuous emission mode for 5 seconds at 1 MHz, once per day for seven days, starting 72 hours after surgery, applied transcranially with water-filled adapter and gel.

Flags from extraction

  • n_subjects — Group sizes of the two ultrasound groups (PC and TM, eight each); 32 rats in total; deaths reduced analysed numbers
  • exposures[0].unspecified_domain.isppa_w_cm2 — Paper gives 'intensity 0.1 W/cm2' without naming Isppa or Ispta or the domain; continuous wave; placed under Isppa
  • exposures[0].timing — Physiotherapeutic device; duty cycle not stated, continuous mode
  • exposures[0].target — Transcranial application over the injection site; target term chosen from the pyramidal tract region named for the injection