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Neuroinflammation contributes to the progression of several neurodegenerative conditions, including Alzheimer's and Parkinson's, affecting millions of people worldwide.

In a new study, Sarina Grewal (a PhD student in the Departments of Brain Sciences and Bioengineering at ÌìÃÀ´«Ã½) in 's group (UK DRI at Imperial) showed that ultrasound can non-invasively reduce brain inflammation by modulating microglial activity. 

The paper, published in , suggests that therapeutic effects are largely dependent on the exact frequency of ultrasound and its acoustic pressure. 

"Brain inflammation is involved in many conditions, but it is difficult to treat. This work shows that ultrasound could offer a new way to reach the brain and target the inflammatory processes, non-invasively", explained Sarina Grewal.

The brain’s immune system  

Although inflammation starts as a protective response, sustained disruption to microglia’s activity can disrupt the brain’s carefully balanced environment. When activated, microglia release signalling molecules that induce inflammation, such as tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and these can cause damage to the surrounding tissue.  

“Reducing brain inflammation without suppressing the rest of the immune system is an ongoing clinical challenge,” said Dr Sopie Morse.  As a result, there is growing interest in safe, non-invasive ways to reduce microglial activation to a normal level. 

Sound waves beyond the range of human hearing, ultrasound can be directed at specific tissues deep within the body. Yet the lack of standardised parameters across studies has long made it difficult to compare results or design reproducible therapies. 

 “Our study shows that ultrasound could be the answer: it is entirely non-invasive, safe, and painless, and allows targeted treatment of brain inflammation while allowing immune cells elsewhere in the body to function as normal. This could be a viable treatment option to reduce brain inflammation in neurodegenerative conditions such as Alzheimer’s and Parkinson’s”, explained Dr Morse.  

Ultrasound silences brain inflammation

To address this, the Morse Lab systematically screened 27 different combinations of centre frequency, acoustic pressure and treatment duration in microglia in a dish that had been placed into a state of inflammation.  

They found that delivering ultrasound at 0.5 MHz at 0.2 MPa for five minutes produced significant and sustained benefits. Levels of the inflammatory signalling molecules remained lower for at least 72 hours after treatment, and gene analysis suggested this was linked to the NF-κB signalling pathway, a key regulator of inflammation. Conversely, at the same time, expression of anti-inflammatory genes IL-10 and IL-4 was increased. The ultrasound reduced markers of cell toxicity, and temperature rises in the tissue were negligible. 

Sarina Grewal and the team then tested the same parameter set in mouse models that mimicked sustained brain inflammation. Just four hours after a single whole-brain ultrasound session, with just 6 seconds of ultrasound, TNF-α levels were significantly reduced in the hippocampus, a region particularly vulnerable to damage by inflammation. The microglia also began to regain their normal, highly branched structure.  

The researchers also observed increased activity within the cells’ lysosomes – the cell’s recycling centre - suggesting they were priming themselves to clear cellular debris, and indicating the cells were returning to a normally functioning state. 

The impact 

"In the long term, the hope is that this research could one day lead to treatments that are easier to receive and given before the disease has caused too much damage", said Ms Grewal. 

Achieving that goal will require careful fine-tuning of ultrasonic parameters, including frequency, acoustic pressure and treatment duration, before the technology can be safely used in patients.

In future studies, the Morse Lab plans to test the approach in disease-relevant models and human microglia models. This work could eventually allow clinicians to tailor ultrasound protocols to specific diseases, and potentially to individual patients. 

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• Reference: Grewal, S., Iacoponi, F., Chan, L.Y.N. et al. Ultrasound modulates microglial activity and reduces neuroinflammation in a parameter-dependent manner. npj Acoust. 2, 15 (2026).  

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