Scientists have developed a nasal spray that reduces brain inflammation and restores lost memory function in mice.
The Texas A&M University research team behind it believes similar results could be seen in people, with further research and development.
The spray targets "neuroinflammaging" – small pockets of chronic stress in the aging brain – which is linked to age-related cognitive decline and is thought to play a role in neurological disorders such as Alzheimer's. The researchers compare neuroinflammaging to parts of an engine that are always running hot.
In the mouse models, the spray targeted these hotspots with millions of microscopic biological bubbles, known as extracellular vesicles (EVs), packed with proteins and genetic instructions and produced from human stem cells.
The mice were 18 months old, an age commonly treated as older adulthood in mouse studies, roughly comparable to humans in their late 50s to late 60s.
"As we develop and scale this therapy, a simple, two-dose nasal spray could one day replace invasive, risky procedures or maybe even months of medication," says neuroscientist Ashok Shetty.
"It's universal. Treatment outcomes were consistent and similar across both sexes."
The researchers wanted to focus on microglia (the brain's immune cells) in the hippocampus, a region crucial for memory and learning, where significant neuroinflammation occurs.
Using healthy stem cells – which can grow and develop into other cell types – is an approach now being widely investigated for its therapeutic potential. It's also been established that stem cell byproducts, such as EVs, can perform much of the beneficial work while being safer to transfer into the body.
In the study, 18-month-old male and female mice received two intranasal doses, spaced two weeks apart.
Delivering the treatment through the nose may help EVs reach the brain more directly without invasive surgical procedures, and the researchers report that they were quickly absorbed.
After the two doses, the treated animals outperformed control mice on tasks measuring object recognition and spatial memory. Further biochemical analysis of the hippocampus suggested the treatment had the desired effects on brain inflammation.
Inside the EVs are microRNAs, tiny pieces of genetic code that regulate gene expression. As these microRNAs are released, they rewire brain cells to turn off or dial down some of the alarm signaling that drives neuroinflammaging.
In aging mice, that meant microglia were able to reset to a more normal state, including how mitochondria (the cell batteries) managed energy.
"MicroRNAs act like master regulators. They help modulate and regulate many gene and signaling pathways in the brain," says neuroscientist Madhu Leelavathi Narayana.
"We are giving neurons their spark back by reducing oxidative stress and reactivating the brain's mitochondria."
New dementia cases in the US alone could hit a million a year by 2060, double the current level, and this study points to a possible new way to reduce age-related neuroinflammation that can spark dementia.
Other animal studies have suggested related EV therapies may also aid recovery after stroke or brain injury.
Human trials will be needed to determine if they can treat conditions such as mild cognitive impairment, but the early signs are promising.
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The findings align with a growing body of research on how we can age more healthily, with less of the biological wear and tear that the advancing years usually bring.
"Brain age-related diseases like dementia are a major health concern worldwide," says Shetty.
"We're aiming for successful brain aging: keeping people engaged, alert, and connected. Not just living longer, but living smarter and healthier."
The research has been published in the Journal of Extracellular Vesicles.