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Multimodal evaluation of the effects of low-intensity ultrasound on cerebral blood flow after traumatic brain injury in mice

Huiling Yi, Shuo Wu, Xiaohan Wang, Lanxiang Liu, Wenzhu Wang, Yan Yu, Zihan Li, Yinglan Jin, Jian Liu, Tao Zheng, Dan Du

BMC Neuroscience 2024 · 10.1186/s12868-024-00849-0

rodenttraumatic brain injurycerebral haemodynamicsbehaviourhistology molecular

Abstract

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects16 animals
Sessions per subject14
Randomisedyes
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutscerebral haemodynamics, behaviour, histology molecular — laser speckle imaging; neurological severity score; Nissl staining; VEGF immunohistochemistry
Direction of effectnot assessedTBI mice receiving tFUS had higher relative CBF and lower NSS than untreated TBI mice across 14 days.
Adverse eventsnot reported

Exposures

Exposure 1: tFUS to injured cortex

Target: cerebral cortex — “target region in the injured cortical areas”
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)2.6✓✓✓⚑
Protocol, in the paper’s words

Unfocused transducer with conical collimator over the injured cortex; total stimulation duration 10 min daily for 14 consecutive days. SD 400 ms, TBD 0.5 ms, PRF 1 kHz.

Flags from extraction

  • n_subjects — 45 mice enrolled; groups listed as sham 6, TBI 16, TBI+tFUS 16 (38) after 7 exclusions; only the 16 TBI+tFUS mice received real ultrasound. Quote spells the number as 'Forty-five'.
  • exposures[0].unspecified_domain.isppa_w_cm2 — Isppa measured with a hydrophone; medium not stated.
  • exposures[0].timing.duty_cycle_pct — Duty cycle not stated; not computed.
  • exposures[0].timing.sonication_duration_s — 400 ms 'stimulation duration' per train with 10 min total; read as train length.
  • sham_type — TBI group received 'sham tFUS' with no mechanism described; sham group was surgery without impact.
  • species — Paper describes mice as C57BL/6; text refers to rats in figure legends (apparent error).