Ultrasound modulates microglial activity and reduces neuroinflammation in a parameter-dependent manner
Sarina Grewal, Francesco Iacoponi, Lok Yin Nicholas Chan, Valeria Dosso, William Lim Kee Chang, Vanessa Drevenakova, Albert Ugwudike, Leonardo Ricotti, Paul M. Matthews, Andrea Cafarelli, Sophie V. Morse
npj Acoustics 2026 · 10.1038/s44384-026-00047-8
Abstract
Neuroinflammation contributes to the progression of many neurological diseases. Here, we explore whether ultrasound can reduce microglia-mediated inflammation in vitro and in vivo. We tested a broad range of ultrasound parameters in a BV2 microglial cell line, treated with lipopolysaccharide (LPS) to induce an inflammatory response. We found that specific combinations of centre frequency, acoustic pressure and treatment duration can significantly lower the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. These effects lasted up to 72 h and were associated with the downregulation of the nuclear factor κB (NF-κB), suggesting a mechanistic link between ultrasound and inflammation. Further investigation in vivo, in LPS-treated mice, revealed a reduction in TNF-α expression in the hippocampus following ultrasound. Overall, our findings showcase the potential of ultrasound as a non-invasive therapeutic strategy to reduce neuroinflammation and restore brain homeostasis.
Abstract via europepmc.
Exposures
Exposure 1: BV2 microglia in vitro, 0.5/1/2 MHz
Target: cultured glia — “BV2 microglial cell line”
Device: other named manufacturer · Precision Acoustics · unfocused piezoelectric transducers, 0.5 MHz (44 mm), 1 MHz (23 mm), 2 MHz (23 mm) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500, 1,000, 2,000swept | ✓✓✓ |
| 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) | 300, 1,800, 3,600swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable | |
| Pressure, domain unspecified (kPa) | 100, 200, 400swept | ✓✓✓⚑ |
Single treatment of LPS-treated BV2 cells at 3 frequencies, 3 peak-to-peak pressures and 3 durations (5, 30, 60 min), duty cycle 20% and PRF 1 kHz; supernatant collected 24 h later.
Exposure 2: Whole-brain sonication of LPS mice, 0.5 MHz
Target: whole brain or unfocused — “whole mouse brain”
Device: Sonic Concepts · Sonic Concepts · H-107 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓⚑ |
| Sonication duration (s) | 6 | ✓✓✓ |
| Free-field pressure (kPa) | 200 | ✓✓✓⚑ |
|---|---|---|
| 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 |
6 s sonication at each point of a grid (8.52 x 14.98 mm) covering the whole brain, 200 microsecond pulses at 1 kHz; a single treatment on day 7, brains collected 4 h later.
Flags from extraction
n_subjects— Mice: saline 3, LPS 4, LPS + ultrasound 4 (11 total, stated as 'Eleven'); in vitro n = 3 wells per condition. Only 4 mice received ultrasound.exposures[0].unspecified_domain.pressure_kpa— Stated as peak-to-peak pressure 0.1, 0.2, 0.4 MPa; domain not stated (in vitro device). Intensities only in Supplementary Table S1.exposures[0].timing.pulse_duration_ms— Pulse duration not stated for in vitro exposure; not computed from duty cycle and PRF.exposures[0].timing.sonication_duration_s— Durations 5, 30, 60 min converted to seconds; a full factorial of 3 frequencies x 3 pressures x 3 durations is one exposure with lists.exposures[1].free_field.pressure_kpa— 0.2 MPa quoted from the acoustic simulation methods (pressure at focus in water); in vivo methods state 0.2 MPa acoustic pressure without domain.exposures[1].timing.duty_cycle_pct— Duty cycle stated in the thermal simulation methods as 20%, matching the in vivo parameters.exposures[1].target.terms— Whole brain covered by raster of a focused beam over an 8.52 x 14.98 mm grid, 6 s per point.direction_of_effect— Outcomes are cytokines and microglial morphology, not neural excitability.