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Neuroprotective effects of low-intensity transcranial ultrasound stimulation combined with Baicalin intervention on traumatic brain injury in animals

Yong Peng, Yang Zhao, Yameng Huang, Xiaoyue Liu, Hui Zhang, Zheng Zhao, Yawei Cheng, Lanxiang Liu

Brain Research Bulletin 2021 · 10.1016/j.brainresbull.2021.07.028

rodenttraumatic brain injuryother mribehaviourhistology molecular

Abstract

Low-intensity transcranial ultrasound stimulation (LITUS) can improve the inflammatory reaction after traumatic brain injury (TBI), and Baicalin also has a good protective effect on TBI. The purpose of this study was to observe the neuroprotective effect of LITUS combined with Baicalin intervention in the TBI rats. Sprague Dawley (SD) rats were randomly divided into 5 groups (n = 15) which were Sham control group, TBI group, LITUS group, Baicalin group, LITUS combined with Baicalin group (LB group). The rats were scanned with 3.0 T magnetic resonance imager, and the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) of the brain injury cortical area were determined at 3 h, 1, 3, 7 and 10 d after TBI. The ADC value, FA value, neurological function score and Nissl staining were used to assess the level of brain damage of rats. The results showed that on the 10th day after TBI, the ADC values of the TBI group, the LITUS group and the Baicalin group were remarkable greater than that of the L-B group (all adjusted P < 0.05), FA values were remarkable smaller than that of the L-B group (all adjusted P < 0.05), neurological function scores were remarkable greater than that of the L-B group (all adjusted P < 0.05), and Nissl body loss rates were remarkable greater than that of the L-B group (all adjusted P < 0.001). This study indicated that compared with the LITUS group and the Baicalin group, the L-B group can more effectively reduce level of brain damage after TBI, and the method of LITUS combined with Baicalin intervention was a more effective neuroprotection for brain injury.

Abstract via europepmc.

Speciesrat (Sprague Dawley)
Subjects15, 15swept animals
Sessions per subject10
Randomisedyes
Blindingdouble
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutsother mri, behaviour, histology molecular — ADC and FA from 3.0 T DWI/DTI; neurological function score; Nissl staining
Direction of effectnot assessedLITUS alone and LITUS combined with Baicalin reduced ADC, neurological score and Nissl body loss and raised FA relative to untreated TBI; the combination was better than LITUS alone. Neuroprotective aim; excitation or inhibition not assessed.
Adverse eventsnot reported

Exposures

Exposure 1: LITUS group (and L-B group)

Target: cerebral cortex — “the brain damage area of the TBI rats”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.5✓✓✓
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 50%
Sonication duration (s)0.4✓✓✓⚑
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)1.2✓✓✓⚑
Protocol, in the paper’s words

Stimulation duration 400 ms and tone-burst duration 0.5 ms at 1 kHz PRF; the probe was placed on the brain damage area for 10 min, first immediately after TBI and then every 24 h at the same time point, a total of 10 times.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2 — Paper gives only an 'average intensity of stimulating pulse'; the intensity type and domain are not stated. Placed as isppa in unspecified_domain by reading 'of stimulating pulse'.
  • exposures[0].timing.sonication_duration_s — The paper states a stimulation duration of 400 ms but also that the probe was applied for 10 min per session; recorded as stated 400 ms (0.4 s). Duty cycle not stated.
  • blinding — 'Double-blind principle' is stated for the neurological function scoring only; blinding of the treatment is not described.
  • anaesthesia — Rats were anaesthetised for TBI surgery and MRI; anaesthetic state during the ultrasound sessions is not stated.
  • exposures[0].device.manufacturer — Olympus named for the transducer V301-SU (Olympus, Japan).