Analgesic Gas Nitrous Oxide Enhances Blood-Brain Barrier Opening for Gene Therapy

UTSW preclinical research combining focused ultrasound with nitrous oxide could improve safe delivery of gene therapy to the brain.
Close-up image of a realistic human brain model with detailed grooves and folds on a light gray background.
The Blood-Brain Barrier is a highly selective border of semipermeable cells that line tiny blood vessels supplying blood to the brain. Unsplash
Published on

DALLAS – Nitrous oxide, a commonly used analgesic gas, temporarily improved the opening of the blood-brain barrier (BBB) to allow gene therapy delivery in mouse models using focused ultrasound (FUS), UT Southwestern Medical Center researchers report in a new study. Their findings, published in Gene Therapy[1], could eventually lead to new ways to treat a variety of brain diseases and disorders.

“The approach we explored in this study has the potential to advance care for diseases of the brain that can be treated by targeted therapeutic delivery.”  

Bhavya R. Shah, M.D., Associate Professor of Radiology, UT Southwestern

He’s also an Investigator in the Peter O’Donnell Jr. Brain Institute and a member of the Center for Alzheimer’s and Neurodegenerative Diseases. Deepshikha Bhardwaj, Ph.D., Senior Research Associate at UTSW, was the study’s first author.

A 3D-rendered head with a transparent top reveals a glowing, detailed brain inside, set against a dark background.
The BBB also impedes the delivery of drugs that could be used to treat neurologic or neuropsychiatric conditions, such as Alzheimer’s disease, multiple sclerosis, or brain tumors. Pixabay
The BBB is a highly selective border of semipermeable cells that line tiny blood vessels supplying blood to the brain. It is thought to have developed during evolution to protect the brain from toxins and infections in the blood.

However, the BBB also impedes the delivery of drugs that could be used to treat neurologic or neuropsychiatric conditions, such as Alzheimer’s disease, multiple sclerosis, or brain tumors. Consequently, researchers have worked for decades to develop solutions that can temporarily open the BBB to allow treatments to enter.

Recently, scientists discovered they could open the BBB in targeted brain areas by intravenously delivering a solution containing microscopic bubbles (microbubbles), then exposing targeted brain regions to FUS. This causes the microbubbles to oscillate, which temporarily increases the permeability of the BBB. However, the concentrations of microbubbles and FUS pressure necessary to open the BBB can pose potential risk to brain tissue.

A scientist in a white lab coat and blue gloves uses a pipette to transfer liquid into test tubes.
As proof of principle, the researchers tested their new approach by delivering a gene that produces a glowing green protein.Unsplash
In the new study, Drs. Shah and Bhardwaj and their colleagues tested a novel approach that significantly reduced the microbubble concentrations and FUS pressure needed to temporarily open the BBB. In mouse models, the researchers tested nitrous oxide, rather than medical air, during the BBB-opening procedure. Nitrous oxide is known to expand microbubbles made of other gases.

Their experiments showed that nitrous oxide required up to 1,000 times lower concentrations of microbubbles and significantly lower FUS pressure to open the BBB compared with air. Lower microbubble doses and FUS pressure posed significantly less risk than the standard procedure.

As proof of principle, the researchers tested their new approach by delivering a gene that produces a glowing green protein. The results showed significantly greater uptake of the gene than when breathing air, seen in a brighter glow from the targeted brain regions.

Two scientists in lab coats and hairnets examine a small container intently.
Recently, scientists discovered they could open the BBB in targeted brain areas by intravenously delivering a solution containing microscopic bubbles (microbubbles), then exposing targeted brain regions to FUS.Pixabay

The researchers’ next step will be to safely test this approach in clinical trials.

Other UTSW researchers who contributed to this study include Marc Diamond, M.D., Director of the Center for Alzheimer’s and Neurodegenerative Diseases and Professor of Neurology and Neuroscience; Rachel Bailey, Ph.D., Assistant Professor in the Center for Alzheimer’s and Neurodegenerative Diseases and of Pediatrics; Sandi Jo Estill-Terpack, B.S., Lab Manager in the Diamond Lab; Darren Imphean, M.D., Radiology resident; and Venugopal Krishnan, Ph.D., postdoctoral researcher.

This study was funded by a UTSW High Impact Grant.

Reference:

1. https://www.nature.com/articles/s41434-025-00530-z

(Newswise/PPP)

Related Stories

No stories found.
logo
Medbound
www.medboundtimes.com