Low-Intensity Pulsed Ultrasound Stimulation Inhibits Cortical Spreading Depression

Nannan Bian, Yi Yuan, Yingwei Li, Mengyang Liu, Xiaoli Li

Cerebral Cortex 2021 · 10.1093/cercor/bhab055

rodentothercerebral haemodynamicsbehaviourhistology molecular

Abstract

Cortical spreading depression (CSD), which is closely correlated with migraine aura, cerebral ischemia, seizure, and brain injury, is a spreading wave of neuronal and glial depolarization. The purpose of this study is to investigate whether low-intensity pulsed ultrasound stimulation (PUS) inhibits CSD by modulating neural activity and hemodynamics. Behavioral test, intrinsic signal optical imaging and western blot analysis were used for evaluating the inhibition effect of PUS on CSD in rat. We found that: 1) 30 min of PUS can significantly improve motor activity of rat with CSD. 2) Both 30 s and 30 min of PUS can significantly reduce count and propagation speed of CSD in rat and the inhibitory effect was enhanced with increase of ultrasound intensity. 3) 30 min of PUS significantly enhanced levels of brain-derived neurotrophic factor protein in brain tissue with CSD. These results suggest that PUS has the potential to treat brain disorders associated with CSD.

Abstract via europepmc.

Speciesrat (Sprague Dawley)

Subjects114 animals

Sessions per subjectnot reported

Randomisedyes

Blindingnot reported

Sham / controlinactive transducer

Auditory controlnot reported

Readout timingboth

Anaesthesiaanaesthetised

Readoutscerebral haemodynamics, behaviour, histology molecular — intrinsic signal optical imaging of CSD count and propagation speed; open field test; BDNF western blot

Direction of effectinhibitoryPUS reduced the count and propagation speed of CSD, more so at higher pressure; 30 min PUS improved open-field motor activity and raised BDNF.

Adverse eventsnot reported

Exposures

Exposure 1: PUS at CSD induction window (30 s and 30 min groups; 0.2-0.8 MPa; DC 20-80%)

Target: motor cortex — “induction window”
Device: Olympus / Panametrics · Olympus · V302-SU ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	1,000	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	1,000	✓✓✓
Duty cycle (%)	20, 50, 80swept	✓✓✓⚑
Sonication duration (s)	30, 1,800swept	✓✓✓⚑

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 estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported
Pressure, domain unspecified (kPa)	200, 400, 600, 800swept	✓✓✓⚑

Protocol, in the paper’s words

PUS of 30 s or 30 min was delivered to the induction window of CSD (1 M KCl) at 1 MHz, PRF 1 kHz, DC 50% at 0.6 MPa; pressure (0.2-0.8 MPa) and DC (20, 50, 80%) were varied in separate experiments with 30 s PUS. Pulse duration is not stated in the text.

Flags from extraction

exposures[0].timing.pulse_duration_ms — Pulse duration not stated in text (tone-burst parameters only in Fig. 1B); not computed.
exposures[0].unspecified_domain.pressure_kpa — Pressure stated without domain; hydrophone field measurement is mentioned but values are not tied to a domain.
exposures[0].timing.duty_cycle_pct — Main protocol DC 50%; 20% and 80% appear only in a supplementary-figure comparison, so the list is drawn from the Discussion sentence.
exposures[0].timing.sonication_duration_s — 30 min converted to 1800 s.
sham_type — Sham: transducer and cone placed horizontally above skull, exit parallel to skull; classified as inactive_transducer (aimed away).
n_subjects — 114 rats in total across all experiments including non-sonicated CSD and control groups.